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Clinical Laboratory Improvement Advisory Committee Meeting Transcript April 14-15, 2021 Atlanta, Georgia U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES

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April 14, 2021 ❖ Call to Order, Recognition of Outgoing Members, and Committee Member

Introductions CLIAC DFO: Good morning, everyone. Welcome to the Spring 2021 meeting of the Clinical Laboratory Improvement Advisory Committee. It is 11:00 AM on the East Coast, 8:00 AM on the West Coast. And we are looking forward to a great meeting today and tomorrow. The Clinical Laboratory Improvement Advisory Committee, or CLIAC, is managed by the Centers for Disease Control and Prevention and provides scientific and technical advice and guidance to the Department of Health and Human Services. The advice and guidance CLIAC provides to HHS pertains to general issues related to improvement in clinical laboratory quality and laboratory medicine practice. In addition, the committee provides advice and guidance on specific questions related to possible revision of the CLIA standards. Because this is a federal advisory committee meeting, the Zoom chat and Q&A functions have been disabled for audience members. If you are experiencing Zoom difficulties, please contact cliac@cdc.gov. I'd like to start this meeting with a very short but important presentation for the clinical laboratory community. Next slide, please. This may sound trite, but it is genuine. I would like to express our appreciation for everyone who has worked in a clinical laboratory through the course of this pandemic, or at any time during the pandemic. We are extremely grateful for the work that you have done. We appreciate how stressful and how difficult the last year or more have been for all of you. However, laboratory testing for SARS-CoV-2 has proven to be incredibly important, if not arguably the most important aspect of the response to this pandemic. And that work is not yet over. Obviously, we're still in the midst of this response. We still rely incredibly highly on our clinical laboratory community. So, I want to express our appreciation and our gratitude for that work. Next slide, please. Next week, I believe, is Medical Laboratory Professionals Week. And we will be celebrating these public health champions who, in particular, work in our clinical and medical laboratories. As of today, the clinical laboratory community in the United States has performed more than 391 million tests for SARS-CoV-2 and COVID-19 antibodies. As I said, the work of this community is incredibly important to the response, and we're extremely grateful. And we hope that we'll be able to make a big splash next week during Medical Laboratory Professionals Week to reinforce the importance of these professionals. Next slide, please. As I'm sure most of you who are attending this meeting know, the efforts of the laboratory testing community have made headlines in news outlets like the New York Times, which have highlighted the importance of the work of clinical laboratory professionals, but also, equally important, the demands that this pandemic has placed on laboratory testing and those of us who work in the laboratory testing field. This news coverage not only elevates these individuals and their importance to the response, but also underscores the importance of the role that CLIA plays in the lives of everyone living in the United States. CLIA sets the standard for quality and reliable laboratory testing for everyone in the United States who receives a test result, regardless of where that test is performed, regardless of what that person looks like, what they think, or how they behave. CLIA establishes that standard, that health equity standard for laboratory testing in this country. And I hope we all can continue to appreciate the importance of CLIA to our clinical laboratory testing community and endeavor. With that, I will conclude this presentation, and we can start the meeting. CLIAC CHAIR: Thank you, Ren. I very much appreciate the acknowledgment and appreciation for what the laboratory community brought forward in 2020. We felt we were unsung heroes, and with your presentation, we are now sung heroes. And that lifts our spirits in times like these. Thank you. Good morning, everybody. I'm Valerie Ng. I'm the chairman of CLIA. And a couple of ground rules. Keep in mind, during the period that is dedicated to our community discussion, participation is limited to us, CLIA members only. For the public, CLIA can only accept public comments that directly relate to the topics announced in the Federal Register notice of the CLIAC meeting, and as related to the theme laboratory medicine in the age of COVID-19. Today, the committee will discuss and deliberate on the following topics-- clinical laboratory perspectives and laboratory developed tests. Public comments are scheduled at the end of each topic area, and for both meeting days. Today, public comments will be limited to a total time of five minutes per individual or group. If anyone in the audience wishes to address the committee, the public comment portion of the meeting is the proper forum to do so. So, members of the public who are attending, if you did not previously send a request for public comment and you would like to participate, please email us now-cliac@cdc.gov to be added to the session. I am here to remind the members of our requirement for quorum. It's important

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that we remain in attendance on both days for the full meeting and we return promptly from breaks to ensure a quorum until all matters before the committee are addressed and the meeting is adjourned. We expect you to keep your video on at all times, with the exception of breaks. Process for official recommendations. Official recommendations are those related to an item on the meeting agenda that are put forward as a motion, seconded by another CLIAC member, voted on by CLIAC, and obtain a majority vote. A reminder that all CLIAC discussions and deliberations must be available to the public. This means the chat box is not available to the public for viewing. So CLIAC members should not engage in topic discussions offline to the chat box. Don't make me bring my finger out. Please use the chat box only to notify me of your desire to comment during the discussions or to ask a question of a speaker. Again, that is to notify that you want to ask a question of a speaker. You have to get in line with everybody else. CLIAC DFO: Thank you, Valerie. We'd now like to recognize the outgoing members of CLIAC. I believe we have a presentation. The outgoing members of CLIAC, who we are extremely grateful to for their time and dedication to this federal advisory committee, are Dr. Marc Couturier, Dr. Steve Hinrichs, Dr. Jordan Laser, Dr. Thomas Lorey, Dr. Katherine Perez, and Dr. Thomas Williams. Please visit the CLIAC meeting website to review this presentation for a detailed list of their contributions to CLIAC. We thank all of you for your service and your dedication. We would also like to thank Ms. Regina Van Brakle for serving as the CMS ex officio during the October 2020 meeting, and for providing the CMS update at that time. Thank you, Regina, for your service to the community. We would also like to recognize that Ms. Monique Spruill is replacing Ms. Regina Van Brakle as a CMS ex officio. Ms. Spruill is the Director of the Division of Clinical Laboratory Improvement and Quality at CMS. We do have one new member joining us and that is Ms. Heather Duncan. And thank you, Heather, for joining the committee, we really appreciate your commitment. Our roster slides listing members is now being shown. We will want to recognize the new members, but they can introduce themselves during the group introductions, and the indications of conflict of interest. Just want to remind you that when you introduce yourselves, please unmute to speak. So, I will call on you and you will introduce yourself. Please keep your introduction short and keep your name, your affiliation, and your conflicts of interest. And for those of you who are new members, please provide a little more explanation of who you are and your background. Dr. Valerie Ng. CLIAC CHAIR: Oh shucks, I have to go first. I'm Valerie Ng. I'm Chair of Laboratory Medicine and Pathology at Alameda Health System. And I am also the Laboratory Director of their clinical labs. I am employed by the East Bay medical group, which is wholly owned by Alameda Health System, and I am on the Board of Directors of East Bay Medical Group. I have been a consultant for CARB-X in the last year and I'm a book editor for Duty Publishing, Incorporated. I'm going to call on Ms. Heather Duncan, next on the list. MS. HEATHER DUNCAN: I'm Heather Duncan. I am the manager of Microbiology and Molecular Diagnostics for Vidant Medical Center. We're a large academic Medical Center serving Eastern North Carolina. My background includes laboratory startups in the realms of government and industrial sectors. I'm very passionate about laboratory quality, and as a certified quality auditor, I have served as a CLIA surveyor. I'm very honored to join this group today and I look forward to all of our exciting discussions. I have no conflicts to close today. CLIAC DFO: Dr. Birthale Archie. CLIAC CHAIR: Birthale, you're on mute. DR. BIRTHALE ARCHIE: Good morning. I am Dr. Birthale Archie and I'm an assistant professor at Bowie State University, and I am over the leadership and transition into professional nursing practice where I work with a cadre of senior students at MedStar Hospital and others. And also, I have a degree in biology and chemistry that I use to facilitate-- I use that knowledge base to facilitate additional learning for our students, so that they're able to integrate the chemistry, biology, and also nursing concepts to graduate more competent practitioners. And so, I'm part of the National Black Nurses Association, and also the Maryland Organization of Nurse Leaders. Thank you. CLIAC DFO: Birthale, do you have any conflicts of interest? DR. BIRTHALE ARCHIE: I do not have any conflict of interest. I shared last time that I had received a grant from the Maryland Department of Health and that one has completed. CLIAC DFO: Great. Thank you, Birthale. Dr. Mark Couturier.

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DR. MARC COUTURIER: Good morning. So, I am an associate professor in the Department of Pathology at the University of Utah where I function professionally as a medical microbiologist. As such, I'm a paid consultant as medical director at ARUP Laboratories, a not-for-profit reference laboratory, also owned by the University of Utah. I have conflicts of interest, as such that I receive household income at the level of my family from BioFire Diagnostics, and own stock in BioMerieux, which is a foreign company. I'm a member of the College of American Pathologists, Microbiology Resource Committee, and the ASCP Choosing Wisely Committees. I have done trial activities with Luminex Genetic Signatures and DiaSorin. I receive research reagents from TechSite and Apicore. I'm a paid editor for ASM press. And I am disclosing I'm quite sad to be leaving this excellent committee, so thank you to everyone. CLIAC DFO: Thank you, Mark. We're disappointed to have you leave, as well. You've been a great contributor. I believe Dr. Mary Edgerton has not yet joined us. Is that true? Mary, are you there? OK, let's move on. Dr. Susan Gross. DR. SUE GROSS: I am Dr. Sue Gross. OBGYN geneticist, adjunct professor at Icahn School of Medicine at Mount Sinai. Division of Genetic/Genomic Science Department of Genetic Genomic Sciences, it's in New York City. The conflicts-- I am employed as Chief Medical Officer of Cradle Genomics, a company that is developing next generation of prenatal genetic tests. I'm also the CEO and President of the ObG project, it's a mobile friendly educational site for health care professionals, promoting best practices and guidelines. CLIAC DFO: Thank you, Susan. Dr. Lee Hilborne. DR. LEE HILBORNE: All right. Good morning, everybody. I'm Lee Hilborne. I am a professor of Pathology and Laboratory Medicine at the David Geffen School of Medicine at UCLA. And senior medical director for the UCLA Health. I am also a senior medical director for Medical Affairs for Quest Diagnostics. And due own stock in Quest Diagnostics as an employee. So that's by way of a conflict disclosure. Other roles, I am past president and serve on a number of committees for the American Society for Clinical Pathology. Including the Effective Test Utilization Committee. I'm on a committee for the CAP, a number of them for the American Clinical Laboratory Association. And I co-chair the Proprietary Laboratory Analysis, a technical advisory group for AMA CPT. CLIAC DFO: Great, thank you, Lee. I believe Dr. Steven Hinrichs has not yet joined us, am I correct? OK, Dr. Jordan Laser. DR. JORDAN LASER: Yes, good morning. Can you hear me ok? CLIAC DFO: Yes, we can. DR. JORDAN LASER: OK, perfect. I am Jordan Laser. I have a couple of positions right now. The medical director for Pathology and Laboratory Medicine at Long Island Jewish Medical Center. This is at Northwell Health based in New York, where I am also the associate professor of Pathology and Laboratory Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. I also have another position. I'm the chief laboratory officer at Everly Health, it's a health tech company. We are providing consumer-initiated laboratory testing and telehealth services. And in terms of conflict of interest, I have an active grant through Natera, studying placental mosaicism. In terms of the Association for Molecular Pathology, I'm the Chair of the Professional Relations Committee, a member of the Board of Directors, and a member of the AMP COVID Response Committee. And through the College of American Pathologists, I am the vice chair of the Personalized Health Care Committee. And just like Marc, I will also disclose that I am quite sad to be rotating off. This has been a fantastic four years, so thank you. CLIAC DFO: Thank you, Jordan, we will also miss you as well. Dr. Thomas Lorey. DR. THOMAS LOREY: Yes, good morning. Tom Lorey. I am a pathologist, clinical pathologist by training, with Kaiser Permanente in Northern California, where I currently serve as the Strategic Director of Integrated Services. America's lab medical directed for Regional Reference Laboratories. I hold a couple of volunteer positions. One is an associate editor for the Journal of Applied Laboratory Medicine. And a volunteered board member for Clin Lab 2.0. I have no other conflicts of interest, financial or otherwise. It's been a pleasure to serve on this committee and I, too, will miss the enlightening conversations, and wish the committee well. CLIAC DFO: Thank you, Tom. We will miss you too. Dr. Lavinia Middleton. DR. LAVINIA MIDDLETON: Good morning. Lavinia Middleton. I'm a professor of Pathology at UT MD Anderson Cancer Center. I serve on the AAMC Diagnostic Accuracy Committee. I have no conflicts of interest, thank you. CLIAC DFO: Thank you, Lavinia. Ms. Carole Moss.

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MS. CAROLE MOSS: Hello, everybody. Good to see you. I'm Carole Moss, and I started focusing on patient safety and learning more and more about our health care system about 15 years ago, when my son, Nile, died of a preventable hospital acquired infection and then his life ended in sepsis. I do believe if there were at-home tests available to the public, I would have been able to understand if my son had sepsis. He could be here today. I'm passionate about improving health care diagnostics to drive faster, more accurate diagnosis for earlier treatment. I have no conflicts of interest, other than I'm here representing the public, and I'm honored to be here with all of you. And I know that this year has been really unbelievable for so many people. But after 15 years of investigating why my son died and how this preventable harm thing happened. Quite frankly, I wasn't surprised of the destruction that's happened to the public and to our health care system, and I'm focused on doing whatever I can to help make change. So, I'm honored to be here with all of you guys. CLIAC DFO: Thank you, Carole. Dr. Nirali Patel. DR. NIRALI PATEL: Hi, I'm Nirali Patel. I'm currently Director of Molecular Pathology at Tempus Labs, a private company doing large scale genomic sequencing. I also serve on multiple committees for the Association for Molecular Pathology. No other conflicts to disclose. CLIAC DFO: Thank you, Nirali. Dr. Michael Pentella. DR. MICHAEL PENTELLA: Morning, I'm Mike Pentella. I'm the Director of the State Hygienic Laboratory, which is Iowa's State Public Health Laboratory. I'm also a clinical professor at the College of Public Health. I have no conflicts of interest to disclose. I'm a member of the Association of Public Health Laboratories, where I serve on multiple committees. And I'm a member of the American Society for Microbiology. I'm very much interested in infectious disease diagnosis; I’ve worked on medically improving many tests throughout my career. I am interested in infectious disease prevention and biosafety. CLIAC DFO: Thank you, Mike. Dr. Katherine Perez. DR. KATHERINE PEREZ: Hi, good morning. I'm an Infectious Diseases Clinical Pharmacist with the Houston Methodist Hospital System. And I oversee and coordinate the Antimicrobial Stewardship Program across our eight hospitals. I'm also an Assistant Professor with the Houston Methodist Research Institute and I am involved in several therapeutic trials with Gilead Pharmaceuticals and the National Institutes of Health. No other conflicts to disclose at this time. Along with some of our other colleagues, I will be rolling off this committee, and I am truly saddened and have really enjoyed my time on this committee as the first pharmacist, as well, to represent our profession. CLIAC DFO: Thank you, Katherine, it's been great to have you as part of the committee, and we hope to have more pharmacists as well. Next, Ms. Jennifer Rhamy. MS. JENNIFER RHAMY: Yes, hello. I have recently retired as the Director of the Regional Blood Center at St. Mary's Hospital, here in Grand Junction, Colorado. As far as disclosures, in the last year I have served on a panel for Instrumentation Laboratory, discussing patient blood management, and have recently written a couple of white papers for the American Association of Blood Management Subsection. CLIAC DFO: Thank you, Jennifer. Dr. Gregory Sossaman. DR. GREGORY SOSSAMAN: Good morning. Greg Sossaman on the System Chair for Clinical Pathology at Auction Health in New Orleans. Also served as the service line lead. I'm a clinical pathologist here. I have conflicts as a volunteer, and a member of the Board of Directors of the ASCP and served on several committees with ASCP. And I'm also a volunteering director member of the Compass Group. No financial conflicts. CLIAC DFO: Thank you, Greg. Dr. Chip Watkins. DR. CHIP WATKINS: Good morning. I am a family doc by training and Chief Medical Officer and Lab Director at Sanesco International and NeuroLab, which is a small kind of specialty lab here in Asheville. Then we also developed, just this past year, a new company called Community Lab, where we actually built that to do COVID testing. Also, Regional Medical Director for Community Care of North Carolina, and we're the vendor for North Carolina Medicaid. I'm an AAFP appointee to the COLA Board of Directors. And also, a partial owner in Southern Grace Distilleries in Mount Pleasant, North Carolina. So, unless things get really bad, there probably won't be a conflict of interest there, but you never know. But otherwise, no conflicts of interest, thank you. CLIAC DFO: Thank you, Chip. Dr. Thomas Williams.

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DR. THOMAS WILLIAMS: Good morning. Tom Williams, and I worked for some 20 plus years as Laboratory Medical Director of Methodist Hospital in Omaha, Nebraska. Retired from that and then served for two years, until 2018, as the State Health Officer and Director of Public Health, Division of Public Health, for the state of Nebraska. Retired from that and then was called back last year when COVID came, so I've been working ad hoc off and on with the state, trying to help as I can with that. I have no conflicts of interest, commercial or financial. I am on the Public Health Association of Nebraska Board. And like everyone else, I'll be sorry to leave this committee. It's been a great experience and a privilege to serve. Thank you. CLIAC DFO: Thank you, Tom, we will definitely miss you as well. Dr. Donna Wolk. DR. DONNA WOLK: Good morning. I am Donna Wolk, the Division Director of Molecular Microbial Diagnostics and Development at Geisinger in Danville, Pennsylvania. It's a rural interdisciplinary health care system and regional reference laboratory. I'm also a professor at the Geisinger Commonwealth School of Medicine. And I serve as the infectious disease sub director-- Infectious Disease Subdivision Director for the Association for Molecular Pathology. As my focus for translational research and rapid diagnostics, I have several research grants and conflict of interest there with Cepheid, DiaSorin, Safeguard Biosciences, Coegin, Sizmek, and MiDEAL And I am an editor for the Clinical Microbiology newsletter from Elsevier. CLIAC DFO: Thank you, Donna. I believe Dr. Mary Edgerton is now on the line. Mary, are you there? DR. MARY EDGERTON: Unmute. I'm unmuted. Can you hear me? CLIAC DFO: Yes, we can hear you Mary. DR. MARY EDGERTON: I am Mary Edgerton. I am a Breast Pathologist and Pathology Information at UT MD Anderson Cancer Center. I also do quite a bit of work with the College of American Pathologists as a volunteer. I chair the PERT committee. I'm a member of the Information Technology Leadership Committee. And I don't have any financial conflicts. CLIAC DFO: Thank you, Mary. Mr. Andy Quintenz. MR. ANDY QUINTENZ: Good morning. My name is Andy Quintenz. I am the industry liaison for AdvaMed. I work for Bio-Rad Laboratories and the capacity of scientific and professional affairs. Some volunteer of such conflicts would be I am on the board of the Clinical and Laboratory Standards Institute. I serve on the AACC corporate advisory board and I am the chair of the ISO Technical Advisory Group, ISO TC 212, which produces standards and documents related to medical devices and laboratories. Thank you. CLIAC DFO: Thank you, Andy Dr. Collette Fitzgerald. DR. COLLETTE FITZGERALD: Morning, everyone. I'm Collette Fitzgerald. I'm the Deputy Director for Science in the Division of Laboratory Systems here at CDC. I'm the CDC ex officio for this CLIAC committee and I have no conflicts of interest. CLIAC DFO: Thank you, Collette. Ms. Monique Spruill. MS. MONIQUE SPRUILL: Hi, I'm Monique Spruill. I'm with CMS as the ex officio. I'm the Director of the Division of Clinical Laboratory Improvement and Quality. And I have no known conflicts of interest, thank you. CLIAC DFO: Thank you, Monique. Dr. Timothy Stenzel. DR. TIMOTHY STENZEL: Hello, everyone. I'm Tim Stenzel from the FDA. And I have no conflicts to report. CLIAC DFO: Thank you, Tim. Ms. Nancy Anderson MS. NANCY ANDERSON: Good morning, everybody. I am Nancy Anderson. I'm the Division of Laboratory Systems at CDC, Senior Advisor for Clinical Laboratories. I am also the Executive Secretary for CLIAC, and I have no conflicts. CLIAC DFO: And last but not least, my name is Ren Salerno. I'm the Director of the Division of Laboratory Systems at CDC. And I am the designated federal official for CLIAC. Valerie, turn it over to you. CLIAC CHAIR: Thank you, everyone, for your introductions. For all of those of you who are rotating off, we will deeply miss you. We are expecting you to remain fully engaged, and in attendance, for the next two days. And since you've been

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on this committee, you're fully aware of how to reach us in between meetings. Even when you are not a member of the panel, you go through Ren, Nancy, and Heather if they're issues you would like us to consider. Schedule logistics, the copies of the PowerPoint presentations and other reading materials are posted on the CLIAC website. That is at cdc.gov/cliac. At the start of each presentation, I will announce the presentation number to assist you in locating the correct electronic file. If you have the agenda up, it is the blue number next to the presentation on the agenda. This meeting is being webcast by a Zoom webinar. We welcome everyone to this virtual meeting of CLIAC. Links for accessing the webinar are provided on the CLIAC website. If you are experiencing any difficulty with accessing Zoom, please email cliac@cdc.gov. The meeting is also recorded to assist in preparing an accurate written summary of the proceedings. And then the final logistical item, there will be an hour break each day. CLIAC members need to arrive online promptly to ensure the quorum so that we can begin the session. I thank you in advance. Moving forward, we will dive into the meeting. And we will start today with updates from our partner agencies, CDC, CMS, and FDA. These are the online presentations, number three, four, and five. Following the agency update presentations, there will be an update provided on recent CLIA recommendations, and a Laboratory Response Network, LRN overview, provided by Dr. Julie Villanueva. Those are online presentations six and seven. We will start now with the CDC update, presented by Dr. Collette Fitzgerald. It's all yours.

❖ Agency Updates and Committee Discussion Centers for Disease Control and Prevention (CDC) Update Collette Fitzgerald, PhD, CDC EX OFFICIO DR. COLLETTE FITZGERALD: Valerie. Good morning, everybody. Thank you for the opportunity to share updates this morning on CDC's COVID-19 laboratory response work, from our COVID-19 Laboratory and Testing Task Force, on the work we have been doing in the Division of Laboratory Systems at CDC-- or DLS, as I will refer to it for the remainder of this presentation-- to support the Laboratory and Testing Task Force and the response. Next slide, please. Since launching an agency wide response to the COVID-19 pandemic on January 20th, 2020, CDC has been learning more about how the disease spreads and affects people and communities. From the beginning of the pandemic, CDC has been at the forefront of sharing what we've learned about COVID-19. The Laboratory and Testing Task Force plays an essential cross-cutting role in CDC's COVID-19 Incident Management System or IMS structure. This Incident Management Structure is how CDC staff deploy internally, within the agency, to respond to outbreaks. We create task forces that are separate from our programmatic organization within the agency. DLS, like all of the other organizational units, divisions, centers, and offices within CDC deploy staff into the Incident Management Structure to support the response. And many of our DLS staff deployed into the CDC COVID-19 Laboratory and Testing Task Force. Our mission as a task force is to increase scientific knowledge about the virus and to increase laboratory testing capacity, and we do this in a variety of ways. It's through work in CDC laboratories, support for Clinical and Public Health Laboratories, and engagement with federal partners, commercial laboratories, and professional laboratory organizations. We have high level functions that are really tied into our mission, which include development of new laboratory tests and procedures, evaluation of laboratory reagents and instruments, the continued development of laboratory technical guidance for the Clinical and Public Health Laboratory community, testing support and technical assistance, and lastly, together with public health partners, CDC is working to detect, track, and characterize variants of SARS-CoV-2. As CDC has learned new information about the variants, the agency has been providing updates to the public and our partners around the world. Next slide, please. The Laboratory Testing Task Force's work focuses around three priority areas. The first priority area is laboratory studies, research, and development. This area work really goes on in CDC laboratories, either directly in the lab or through collaboration with external partners. Aligned with our mission to help increase laboratory testing capacity, is to evaluate different sample types with our current molecular diagnostic test, to get those validated, and also continue to validate new reagents and platforms. Also includes collaborating with partners to evaluate new technologies for SARS-CoV-2 detection. The second priority area is laboratory testing and support. The support that we can provide through specimens that are submitted directly to CDC for diagnostic testing and/or for sequencing to support either surveillance efforts to identify potential variants of interest and variants of concern, or to support cluster investigations and transmission studies, or through the materials that we ship out from our supplies. The third priority area is a big bucket called Guidance and Technical Support, where all of that lab work, the research, the engagement, the collaboration, they really come together so that we at the agency, and our scientific subject matter experts, are able to provide that technical assistance, such as advising partners on testing strategies in different scenarios. We also develop guidance-- which comes in the form as

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guidances published on our website-- may also be frequently asked questions, as well as responses to inquiries. Next slide, please. Some activities that are underway right now include the continued evaluation of alternative procedures, instruments, platforms and reagents for diagnostic tests. We're also currently developing a new interactive COVID-19 viral testing tool. This interactive web-based tool is designed to help individuals make decisions about COVID-19 testing types and next steps. Another area that is really supported by the work that we do in DLS is development, or updating guidance or resources, that are posted at our external website to support laboratory testing. I will be sharing what is new later in this talk, on that. And lastly, the task force will continually work to support testing when specimens are submitted to CDC and to provide technical and technical support and deployments to the field. Next slide, please. So, viruses constantly change through mutation and this includes SARS-CoV-2. New variants of the virus are expected to occur over time. Some variants can spread and become predominant while others subside. We've seen this from seasonal influenza and other viruses in the past. In the United States, CDC uses genomic surveillance to track and analyze emerging SARS-CoV-2 variants with the following approaches shown on this slide. By leading the National SARS-CoV-2 Strain Surveillance, or NS3 System. Since November 2020, CDC regularly received SARS-CoV-2 positive samples from state health departments and other public health agencies for sequencing, for the characterization, and evaluation. On January 25, 2021, the NS3 System was scaled up to process some 750 samples per week at CDC. Also includes partnering with commercial diagnostic laboratories. CDC is contracting with large commercial diagnostic laboratories to sequence samples from across the United States. CDC has commitments from these laboratories to sequence 6,000 samples per week, with the capacity to scale up in response to the nation's needs. Also, through supporting state, local, territorial, and tribal health departments. Since 2014, CDC's advanced molecular detection program has been integrating next generation sequencing and bioinformatics capabilities into the US Public Health system. Several state and local health departments have been deploying these resources as part of their response to COVID-19. To further support these efforts, on December 18, 2020, CDC released $15 million from COVID-19 supplemental funds for the Epidemiology and Laboratory Capacity program. State and local public health laboratories are already sequencing approximately 4,000 samples per week. Also partnering with universities, CDC has contracts with seven universities to conduct genomic surveillance research in collaboration with public health agencies. And lastly, CDC is leading the SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology and Surveillance, or SPHERES consortium. In total, CDC will invest nearly 200 million to increase sequencing and expand genomic sequencing capabilities, such as bioinformatics, reporting, and modeling. Next slide, please. CDC's COVID data tracker website houses a national genomic surveillance database showing the number of published SARS-CoV-2 sequences. The bars on this graph represent the number of SARS-CoV-2 sequences, available in the public repositories at NCBI and GISAID each week since December of 2020. The dark blue bars on the bottom of the graph shows sequences published at public repositories by the NS3 program, the CDC sequencing contracts, and other CDC sequencing efforts. The lighter blue bars on the top show the sequences published to the public repositories by state and local public health laboratories. The horizontal line marking 7,000 sequences represents CDC current weekly sequencing goal. The published sequences are reported by week ending date and sequences generated by CDC and contract labs are available to inform public health actions before they are published. Next slide, please. This slide shows the SARS-CoV-2 variant circulating in the United States from January 3rd to March 13th, 2021. The data in the bar chart shows the estimated bi-weekly prevalence of the most common SARS-CoV-2 lineages circulating in the United States, based on greater than 40,000 sequences, collected through the CDC's National Genomic Surveillance Program since December 20th, 2020 and grouped into week intervals. Variant proportions are adjusted using statistical weighting to correct for the non-random sampling of sequencing data over time and across states, and to provide more representative national estimates. The lineage table on the right shows the lineages that are circulating at or above 1% in the US, along with the current variance of interests, and variants of concern percentages based on proportion. Other lineages represent more than 200 different lineages that are each circulating at less than 2% of the viruses during the period analyzed. Percentages are based on CDC surveillance samples collected between February 28th and March 13th, 2021. Next slide, please. So, in addition to supporting the many task forces across the CDC IM response structure, through redeployment of staff, DLS given its responsibility to the Clinical Laboratory Community, created a response team to specifically provide support to the Laboratory Testing Task Force. This DLS response team is a function, or arm, of the Laboratory Testing Task Force and has responsibilities in the following areas. To lead the tri-agency task force for emergency diagnostics, to provide clinical laboratory technical support, to improve clinical laboratory communication outreach, to develop and support public private partnerships, to provide policy support, to provide training and education development , support. and lastly, to provide repository services. And I will be spending the remainder of my presentation going into more details on some of these activities. Next slide, please. So, starting off with laboratory testing and reporting guidance. Next slide, please.

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This slide shows three new guidance pages on the CDC website and they include the nucleic acid amplification tests webpage that went live on March 28th, 2021. The technical guidance for reporting SARS-CoV-2 sequencing results went live on April 9th, 2021 and provides detailed instructions and examples of how to report SARS-CoV-2 sequencing results to state, local, tribal, or territorial public health departments. And lastly, a biological risk assessment web page went live on March 31st, 2021. Next slide, please. CDC has also updated laboratory guidance for a number of our webpages. On March 11th, 2021, the testing strategies guidance for SARS-CoV-2 webpage was updated. This guidance describes and compares different types of SARS-CoV-2 testing strategies, including their intended use and applications, regulatory requirements, and reporting requirements. On March 17th, 2021, the interim guidelines for COVID-19 antibody testing was also updated. Links to both pages are shown here on this slide. Next slide, please. Three additional guidance webpages have been updated recently and you can see them listed here on this slide with associated links. It includes the guidance for SARS-CoV-2, points of care, and rapid testing, which was updated on March 8th to include revisions to the regulatory requirements for point of care and rapid testing section and the addition of new training resources for manufacturers of SARS-CoV-2 point of care and rapid tests. The intro guidelines for collecting and handling of clinical specimens for COVID-19 testing was updated on February 26, 2021, now includes new guidance on capillary fingerstick specimen collection. And lastly, the testing overview update page was revised on March 17, 2021 and includes expansion on description of categories of tests, choosing a test, and addition of intended uses of testing, additional health equity considerations related to testing, including discussion on ensuring equitable testing access and availability, discussion testing of vaccinated individuals, an interpretation of test results, and inclusion of links to setting-specific testing guidance. Next slide, please. To increase stomatic interoperability for laboratory reporting for detection of SARS-CoV-2, on the LOINC In Vitro Diagnostic or LIVID test code mapping guide, the SARS-CoV-2 test was developed by a core group of SHIELD members. For those who may not be familiar with SHIELD, this is a multi-stakeholder public-private partnership and stands for the Systematic Harmonization and Interoperability Enhancement for Laboratory Data Mapping is based on links SNOMED and HL7 seven standards and was first posted to the DLS website on April 28, 2020 and is updated weekly. All tests that receive FDA e-label authorization are automatically mapped and included in the tool. As of March 17, 2021, 674 qualitative tests have been mapped. You may note that it is more than the number of tests listed on the FDA e-way website. This is because some tests may receive authorization that include multiple IBD devices, and a separate line item is used to identify each device. The number of downloads of the tool has steadily increased since the table was identified in the HHS CARES Act Reporting Requirements, and the tool has over 27,797 downloads as of March 23, 2021. DLS would like to thank this core SHIELD group for creating the rules to consistently apply the standards to map the data elements in the table. Next slide, please. So, moving now to partnership communication and outreach. Next slide, please. Our partnership with other organizations is critically important. We share biweekly calls with the tri-agency task force for emergency diagnostics. We have calls from the American Clinical Laboratory Association, or ACLA, and large commercial laboratories, the Association of Public Health Laboratories, or APHL, and the Council for State and Territorial Epidemiologists, or CSTE, once a month to provide updates on laboratory testing and answer questions from the clinical laboratory community. We participate in calls every two weeks with the APHL and the CDC Laboratory and Testing Task Force and public health laboratory partners, and we have ongoing calls with our federal partners at FDA and CMS as needed. Next slide, please. Related to clinical and public health laboratory issues, in 2017, DLS created, and now biannually convenes, the Clinical Laboratory Partners Forum to strengthen relationships and facilitate communication. We've used this forum to encourage over 25 partners, many listed here on this slide, to share our LOCS messages and COVID-19 content. Many partners from the organizations listed on this slide have presented at our clinical laboratory COVID-19 response course. The partnership between DLS and the many professional organizations has had a positive impact on thousands of clinical and public health laboratories, point of care testing sites, and laboratory personnel nationwide since the pandemic began by providing critical and time sensitive information needed for COVID-19 testing. On March 29, 2021, the partners convened to discuss a variety of topics, including one lab-- and I'll be sharing more on this topic later --SARS-CoV-2 variants, CLIA and SARS-CoV-2 surveillance, and health equity in the laboratory. Next slide, please. Our Laboratory Outreach Communication System, or LOCS, allows clinical laboratories to access specific information and get technical support from CDC. LOCS currently provides laboratories with a forum in which to ask questions and receive information. Email distribution has grown substantially. Currently, there are over 100,000 LOCS subscribers compared to 500 subscribers when I last gave this update at the fall CLIAC meeting in 2020. To date, DLS has distributed 128 COVID-19 SARS-CoV-2 related LOCS messages during the response. LOCS website is the most visited DLS website to date during the response. To opt in is very easy. You just need to email locs@cdc.gov. Next slide, please.

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The clinical laboratory COVID-19 response calls provide a communication platform for CDC, other federal agencies, and partners to engage with and provide the most up to date COVID-19 information and guidance of clinical laboratory community. We started these calls in mid-March 2020 as weekly calls and then moved to a bi-weekly schedule in June 2020. To date, there has been 33 calls with around 1,300 participants per week, and we've received 1,400 plus total questions from these calls. Next slide, please. Since February 2020, we've received over 1,100 inquiries from clinical, academic, public health, and clinical laboratories. As you can see from the bar chart on the left-hand side of this slide, most inquiries, 90%, come from clinical laboratories. The bar chart on the right-hand side of this slide shows the breakdown of inquiries by topic area. You will see that 63% of the total number of COVID-19 inquiries we have received since February 2020 have been related to data and reporting and testing. Next slide, please. This is a bit of a busy slide, but this shows the trend in the types of questions we received in DLS over time up to March 25, 2021, and this has changed over time. In the early part of the response, we mostly received fire safety inquiries and emergency use authorization, or EUA inquiries, as shown by the deep pink and light green bars. But over time, data and reporting, the dark blue bars, and testing inquiries, light gray bars, have become more common. Next slide, please. So moving now to policy. Next slide, please. CDC and all federal agencies are held accountable through a variety of methods. Some of the most common mechanisms are record requests by the Freedom of Information Act, or FOIA inquiries, the Government Accountability Office, or GAO, and Office of Inspector General, or OIG. Our DLS policy office continues to receive and manage FOIA, OIG, and GAO requests that come from a variety of sources related to the COVID-19 response. Most recently, we provided technical assistance to GAO for the July Coronavirus Aid Relief and Economic Security, or CARES Act, report. Responses to these types of requests require coordination between the CDC Laboratory Testing Task Force and the DLS policy offices given the overlapping staff and complementary mission. Next slide, please. DLS policy continues to be engaged during the COVID-19 response and has also responded to several requests in support of the new administration. Examples of DLS policy engagement are highlighted in the slide and include supporting the CDC director speaking engagements. DLS policy has contributed to talking points and opening remarks for Dr. Malinski related to the response for numerous meetings and partner events, such as the APHL board of directors meeting, and the ACLA 2021 annual meeting. DLS policy continues to engage in tracking and monitoring legislative actions as well. For example, the VALID Act, the Improving Diagnosis in Medicine Act, the LIFT America, or Leading Infrastructure for Tomorrow's America, Act, and the Right to Test Act. Next slide, please. So, moving now to CDC's Data Modernization Initiative, or DMI. Next slide, please. Data modernization is a priority for CDC, and efforts are underway to build, streamline, and strengthen data exchange between clinical laboratories, public health, and private health care systems. CDC is at the heart of a national effort to create a modern, integrated, and real time public health data and surveillance that can protect us from any health threats. FY 2020 Appropriations provided CDC with $50 million to modernize its IT and data systems. FY 2021 Appropriation provided CDC with $50 million to continue data modernization activities. DMI has congressional support and is the first ever funded mandate dedicated to modernization accelerated by the CARES Act. We've provided an additional $500 million to CDC to advance surveillance goals for the nation. Next slide, please. CDC's DMI priorities are listed in this slide and include getting data to state, tribal, local, and territorial, or STLT partners. This includes technical and policy solutions for timely complete and accurate data from electronic health records, laboratory, and other primary data sources to STLT partners. Data to CDC, streamlined, coordinated, and interoperable public health reporting by our API gateways, supporting timely complete and accurate bidirectional data flows between state, tribal, local, and territorial public health partners. Through building a public health workforce for reskilling, upskilling, recruitment, and retention of a data science workforce with skills to design, implement, sustain, and innovate data modernization efforts. And lastly, ongoing data modernization and innovation. Leveraging state of the art analytics and visualization capabilities to integrate data from new or nontraditional sources with minimal IT assistance to strengthen the detection response and prevention of health threats. DMI includes funding for Enhanced Laboratory Data Exchange for eTour. And DLS is involved in this effort. CDC's vision of a national eTour system is to implement a single laboratory test ordering and resulting standard that all clinical and public health laboratories will be able to plug into. We look forward to sharing more progress on DLS's effort to advance eTour in the near future. Next slide, please. So, moving next to laboratory training. Next slide, please. At the fall CLIAC meeting 2020, I had mentioned that DLS was preparing to launch the One Lab Initiative, a unified response to training needs in partnership with CDC's COVID-19 Laboratory Testing Task Force. The intent of the One Lab Initiative is to strengthen inner connections between clinical, public health, and CDC laboratory education and training

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professionals to collectively support the rapid, large-scale responses. The long-term goal, beyond the COVID-19 response, is to establish a sustainable learning community to help equip the laboratory workforce with necessary tools, resources, and networks. Next slide, please. Over the next two years, this project has five components, to establish a two-way network with clinical laboratory education and training professionals by leveraging existing partnerships, to conduct an education and training needs assessment, focus on COVID-19 in collaboration with clinical laboratory education and training partners, to design, develop, and evaluate rapid and longer-term educational and training resources for the clinical laboratory community through clinical laboratory workforce, to conduct wide scale dissemination of education and training resources which includes building a learning management system specialized for clinical laboratory professionals, and lastly, tying back to our long term goal, creating an ongoing learning community for clinical laboratory education and training professionals by leveraging the ECHO model. Next slide, please. The One Lab Network launched in January 2021 and has met twice so far. As of March 23rd, there are currently 1,767 members signed up, and interest continues to grow. Network members include representatives with responsibility for education and training within clinical laboratory professional organizations such as ASCLS and ACC, manufacturers, commercial laboratories, and hospital systems. We also have some members from the public health laboratories, particularly those who work with sentinel laboratories. Next slide, please. One Lab Network benefits include having opportunities to provide CDC direct feedback on training needs. One Lab Network members will also have access to newly developed and disseminated education and training resources based on outcomes of the training needs assessment to existing CDC resources relevant to the COVID-19 response. [AUDIO OUT] communication with CDC and other partners in the network and facilitated space in which to exchange lessons learned and better practices for training and workforce development. Next slide, please. Since the launch of the One Lab Network in January, the kickoff meeting took place on February 5, 2021. Immediately after the meeting, a training needs assessment, specific to COVID-19 was open for all members to complete. Data collection closed in late February. A second meeting took place in March in a roundtable format which allowed members to better engage and collaborate with each other. The next meeting will be April 23rd, during which the results from a training needs assessment will be shared. Next slide, please. To learn more about the One Lab Initiative, particularly if you'd like to know more about the training needs assessment results that will be shared soon, please visit cdc.gov/onelab. You can also send us any questions or feedback at onelab@cdc.gov. Next slide, please. Please also visit at cdc.gov/labtraining where you will be able to access 30 e-learning courses from a variety of laboratory topics including COVID-19 relevant courses and job aides. You will also be able to access the latest news about our virtual reality project which is still in progress. A virtual reality course on PPE will be released in September. We also plan to deploy a program that will assist about 40 laboratories across the nation to become VR ready by supplying them with the necessary virtual reality equipment for their staff to access CDC virtual reality courses. Next slide, please. I'm also happy to announce the release of our laboratory e-learning syndication system. If you would like the ability to syndicate CDC laboratory courses when you're on a learning management system, please visit us at the website shown here on this slide. Next slide, please. And last but not least, I'd like to let you know that we're working on yet another new and exciting resource, the One Lab Reach, or rapid education and capacity building hub. We're working on designing a new learning management system specific for COVID-19 laboratory education and training resources. We're hoping to release this system by the fall. Continue to check the One Lab website for updates on all related resources, including the One Lab Reach, and please continue to share your feedback with us as this initiative continues to evolve. Next slide, please. I'd just like to end by echoing what Dr. Salerno had said at the outset of the meeting taking the time to first thank our partners, all of the laboratory community for your hard work collaboration and support this year as we continue to work together to respond to the COVID-19 pandemic. I'd also like to acknowledge the expertise, dedication, and hard work of my many colleagues from DLS and across the agency who worked tirelessly in the laboratory and testing task force and other task forces in our instant management structure to support our agency's response to the COVID-19 pandemic. Thank you. CLIAC CHAIR: Thank you, Dr. Fitzgerald. So informative, very much appreciate all the CDC is doing. Thank you. We will hold questions until the end of all the presentations. Ms. Spruill, the floor is yours.

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Centers for Medicare & Medicaid Services (CMS) Update Monique Spruill, MS, CMS EX OFFICIO MS. MONIQUE SPRUILL: Thank you. We'll go to the next slide, please. This is the disclaimer slide. We can also move forward. Today, we'll be talking about the reorganization of our division that took place in October 2019. Our current CLIA enrollment and certification statistics from our CLIA website updates that we had and how you exactly would find information for our regulations on the current unified agenda. Next slide, please. The reorganization of our division took place in October of '19. We are housed within a quality safety and oversight group, and it's frequently known as Q-SOG. And our division is called Division of Clinical Laboratory improvement and Quality. With this reorganization, we went from a regional approach to a location approach. We now have five branches which include two policy branches and three operations branches. Our policy development for our regulations and our guidance is actually all housed within our policy branch, and then our CLIA regulations work group staff is also housed within this policy branch. Our CLIA surveyors are housed within our operations branch. Can we go to the next slide, please? You'll see that we have two administrative assistants, and Regina Van Brakle is our policy branch manager, and also Amy Zale is our other policy manager. We have Dan Hesselgesser who is our operations branch manager, and Ronisha Blackstone who is our other operations manager and also Karen Fuller. Particularly here we wanted you to pay attention to that actually CMS, right now, for our locations, they're actually CMS Atlanta and Dallas, and also that would be underneath Dan Hesselgesser. And also having Ronisha Blackstone, she is over our particular locations in Boston, New York City, Philadelphia, and Chicago. And Karen Fuller would be your contact person for your Kansas City, Denver, San Francisco, and Seattle locations. And so, with this reorganization structure that we have right now, we're actually coming together and working strategically on four major areas. How do we use data actually to increase co-collaborator quality? How do we actually go forward with engaging our stakeholders? And also, within our operations branches, which is our house, our enforcement branches, how do we move forward with looking at consistency with how we move forward with our enforcement actions? And also engaging with our state agencies, and how do we actually get this communication with our stakeholder engagement community and also with our regulations group, we'll speak about this later also with our policy branches. Can I have the next slide, please? Here we wanted to show our current CLIA statistics, as for certificate enrollments, the first line there, you can see that we actually have a large number of strictly certificates for laboratories, nearly at 300,000. Please make a special note up there that this is actually dated. It says March 2021. And so, with these 300,000 laboratories that we actually have oversight over and that we're working with. Of those, we know we have two exact states. That would be New York state and Washington state nearly having 12,000 certificates. And the next line there where you'll see actually nearly 300,284, that would be our total for non-exempt, and these with our next four lines there that 284 would actually be the total there. So, if you look at this now, we actually have nearly 220,000 certificate of waiver laboratories which is extremely large number that we have oversight with. And our PPM laboratories that we have is actually nearly 30,000. And so, you can see, clearly sense of public health epidemic, how we've actually had an extremely large group of ours to fit a waiver laboratories. And then we also have our certificate appliance laboratories with nearly coming in now at 18,000, and also with our accreditation organizations, with a certificate of accreditation nearly at 16,000. And again, our statistics are current as of March 2021. Next slide, please. And this is just a graphic, so you would actually be able to really pay attention to this now and be able to look at our percentage of the total of our certificate types where we'd actually say, yes, 76% of our certificates of that nearly 220,000 that they're actually the certificate of waiver. And also, our-- well, go back. I'm looking at the smallest percentage to larger percentage. With our accreditation organizations coming in at 6% and also at 7% for our certificate of compliance and then our PPM laboratories at 11%. But if you notice that the certificate of waiver being 76%, this is what the impact here is that we want to know since March of 2021 that this is our largest percentage of certificates that we have. Next slide, please. Now we wanted to really highlight, since the public health epidemic, what has exactly happened? Starting with this point of really being at March of 2020, what has our enrollment really looked at overall? So, this first line here, you want to know the total number of laboratories that have enrolled in CLIA since March of 2020 has been around 38,000 laboratories that got time. And then we'll know exactly why our certificate of waivers have actually increased. We have approximately 35,000 new enrollees for certificate of waiver since the public health epidemic. And then a larger portion that we want to look at and highlight these next three rows here, below the certificate of waiver-- our physician office laboratories, we have approximately 8,000 enrollments; for our pharmacy laboratories, we have nearly 5,300 pharmacy laboratories that were enrolled; and also are assisted living facilities with having 4,800. And we really know they were really called upon during this public health emergency, and as COVID was spreading that these laboratories, you can see that these enrollments is clearly reflective of-- and even looking at our home health agencies of actually having enrollment coming in nearly at 12,000. So but really paying attention here to actually really having our system and having a response and having a

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number of nearly 35,000 certificate of waiver laboratories coming in since March of 2020, and actually having the team there at CLIA before I was employed at CMS really happened to respond to this public health emergency. Next slide, please. And here we wanted to show you exactly just our website and some things that did take place in our brochures that we were updating in order to respond to this public health emergency. One of them would have actually been how to obtain a CLIA certificate, which is the first line there. That was actually produced in August of 2019, and this was actually received from the public. And actually, we were having our LabExcellence mailbox and having a lot of questions of exactly how do you obtain your certificate? So, we wanted to actually be able to provide this for laboratory community or any other new laboratories or facilities that were coming on board. The next thing that was actually updated, which was also in August of 2019, the second one there was actually how to obtain specifically a certificate of waiver. You can see from this large influx of certificate of waiver laboratories that may be actually handling this as a correspondence and being able to send it out by email and actually just being able to answer questions on doing a public health emergency of how we move forward. And the other thing that was updated later on was in November 2019 was the Calibration and Calibration Verification brochure that is a middle part there where you can see it. And that was actually updated also. And then the next thing, the Verification of Performance Specifications was actually updated in January of 2020, and you can see that all of these things were actually just trying to respond to the public health emergency and actually engage stakeholders in a lot of questions that we were actually having come in to the office, and the team was able to respond. Next slide, please. In response to the public health emergency, we also moved forward with actually placing two banners on our website. We wanted it to be actually really having individuals have it really easy to find and wait in order to actually be able to pay their certificate fees, and also we constructed a certification guide as a QuickStart reference in order to be able to respond better to individuals who were having questions. Then we could actually, if there were phone calls or any emails, guide them through the process, and they didn't have to actually go through and be confused with trying to find this information anywhere else. So, these banners actually serve well. Banner was placed on the website in September of 2020, and also to pay CLIA fees, it actually goes over to another side which you'll see later on, which is a paid .gov facility that we actually incorporate with. Next slide, please. And now you can see where there's banners. So, they're actually able to clearly go in and just begin the process. It gives them the step by step process. We're actually able to go in and play their laboratories or fees and actually just being able to access this information pretty easy. And we can describe the process more to the laboratories as they were actually coming aboard in order to be able to respond to the public health emergency. Next slide, please. This was one of the most useful guides I think that was ever put forth. And when I was coming on board, I really actually enjoyed reading this guide, in particularly because if you were not familiar with the CMS 116 form, this was a step by step walkthrough process. And it really served well during a public health emergency where we could actually-- this was actually placed out in September of 2020. And this Quickstart guide just moving forward, we're still getting questions and still being able to send this correspondence out and having just individuals find this information. On the first part there, it just actually gives you the guide to CLIA certification. You can actually download and complete this form. And then obviously some general information, and also, we have some different laboratories around the country. They're just able to use this form, and also with having our operations groups as we move forward, our operations groups are able to go and work with our CLIA state surveyors. And so, you have various parties within CLIA that are actually able to distribute this information, this Quickstart guide. So, this has served well for CLIA. We'll go to the next slide, please. And on this we've actually released some recent memos, and in particularly one of them that I wanted to highlight is that we are actually back out surveying in our hospitals. And on the CLIA website-- I'll review these in more intensely tomorrow --but you can actually go there and just find our Quality Safety Oversight Memos. And these are just a few things that you'll find within our guidance. And so being able to access this information on a website, we were actually able to distribute this information out to the stakeholder community and our clinical lab community, and they're actually able to know exactly what processes we're changing and what are we updating, and we've had a lot of updates to the team. In particularly, Regina Van Brakle and Amy Zale have put forth for CLIA for these Quality Safety Oversight Memos. Next slide, please. I want to take some time here to say for-- as our division in October as we were coming back and forming and just really going through and seeing what are our next steps and how are we going to better engage our stakeholders and partners, in particularly, we wanted to know the stakeholder engagement and this partner engagement were extremely important to us. We work with our accreditation organizations, and we have monthly phone calls with them. And on these phone calls were able to determine what exactly is happening in on its grassroots level with our COVID-19 response and exactly what are they facing, the challenges that they actually face going out and conducting surveys. And also, with our state agencies, were actually having quarterly calls with actually at the division level. But actually, on another level within our operations groups, they're actually engaging with our state surveyors on a daily basis. And there are also monthly calls

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that are set up, and they're still interacting with our regions. And so, we actually are able to get a lot of information about our COVID-19 response from our accreditation organizations and our state agencies. And then also just heard, right before me, exactly all of our interactions that we have with our partners. And we're also addressing the laboratory community also. And this is the area we really want to increase our stakeholder engagement with, and so part of our strategic initiatives moving over for the next two years, stakeholder engagement and as partner engagement that will look at exactly. Having individuals-- one part of it is that we have a group of individuals that go out and speak at universities and to others who are interested in coming to the laboratory community, a lot of individuals have never heard of CLIA, and so that's a part of this. It's taught in a course in a University setting or wherever you're at for a brief amount of time. But having a full understanding of CLIA and how to respond and moving forward when they are in the laboratory community is part of that stakeholder engagement, really bringing forth the accountability of our program and awareness and compliance with our CLIA regulations as we move forward. That's what we really want to actually move forward with and be able to have an ongoing conversation with our stakeholder and partnership community. Next slide, please. Right now, we have actually set forth where we're looking at CLIA communications that with our list server, and the goal here is really to be able to disseminate information. So, as we get these memos and guidance and these frequently asked questions exactly how is this actually being communicated out? We have them on our website, but then we're actually able to go forward and communicate with our stakeholders through our communications listserv. We actually have approximately now 20,000 individuals who have signed up with our listserv, so we're able to go back and will be to conduct the analyses and with our COVID-19 responses and exactly what questions have come in and in generally, what questions come in to our listserv and what we're giving this information back out. We also have an email address where we're actually receiving through our lab excellence mailbox. And with this total system right now, we'll go back through it for stakeholder engagement and for compliance assistance, what questions are we getting in and what information can we actually put forth and actually communicate with our stakeholder community because this type of analysis as part of our next strategic initiatives is what we'll be moving forward with. So, I wanted to just highlight this particular listserv and to make sure that everyone knows of it so they can actually sign up for our listserv also so we can disseminate information. Next slide, please. Once you confirm with on our listserv, we just wanted to show this is one of the things that we've actually been able to set forth through the confirmations, through our subscriptions, that we actually get out. Go through our next slide, please. This is an example for a listserv, and this was actually a place for that you were actually able to pay your fees online and just disseminate this information, even though we did have an enforcement discretion for being able to pay your fees and move forward with laboratory testing. So CLIA would not serve as a burden, but as we're moving forward now, and we still do have this enforcement discretion in place, but individuals, they just had questions. So if we're able to disseminate small pieces of information that might be confusing to the laboratory community, we can actually get them CLIA certified and also when they have questions concerning our regulations-- and actually our compliance assistance, this is another thing as we move forward, they'll actually be able to disseminate this information. I'll go onto the next slide, please. Really with our regulation’s assessment, right now we have an internal process where we're looking at where are our priority areas for CLIA. We've known that CLIA was actually birthed in 1988, and some of these regulations, right now we know that there are laboratory practices and updates that we currently need to look at internally. So, we're doing a full examination of our regulations with an internal process as part of the next strategic strategies we'll have over the next two years. In particularly, we wanted to highlight here was the regulatory assessment work group. This work group was formed in April 2019, and there were actually three work groups, three CLIA work groups. Initially, it was personnel, the next generation sequencing, and your nontraditional testing workflow. And so these discussions took place, and we really wanted to move forward with these recommendations and say, how do we take these three work groups, the work that they've had, and then go forth with and actually just engage others and really set up those priority areas and make decisions upon what regulations do we need to move forward with, in particularly with CLIA. How we make our regulations better? How do we respond to the current times that we actually have? And so, what we wanted to do was go back in from those three work groups and actually come forward. And this body was actually charged with advising HHS. How CLIA might specifically be upgraded, integrated, and reflecting on the reports of those three different work groups? And for us where our priority areas lying at, and what regulations would you like to move forward with? A lot of times we get questions about what's happening next with our regulations. So, I'll go on to the next slide here. So, individuals would be able to know that you wouldn't have to ask questions of per se anyone at CMS. You can actually go through on regulations.gov, and every year there's a unified agenda and regulatory and de-regulatory actions that are set forth. And if you select the agency of HHS and the organization as CMS, you can actually know what regulations and proposed rulemaking, or final rule. Or any other actions that we're moving forward with, you can find them here. Can I have the next slide, please?

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And this is actually just our fall 2020, and this is just showing you, if you go onto this website and if you actually select the Department of Health and Human Services, and then I'll go onto the next slide also. And then if you actually type in CMS that you would actually be able to find all of our regulations actually just press in that search feature. So, for our regulation and also through this regulatory update, you can actually get have notes sent. They send you notifications of exactly when CMS will be updating any regulations. So, you'd actually be able to go here and find all of our regulatory guidance and updates. The next thing that I want to really speak about is our consistency within our enforcement arm. As we're working with state agencies now, we'll actually go through and really conduct an assessment of how do we increase our compliance assessments assistance and with our state agencies and within the laboratory community. So, they would actually be able to know that we're actually able to better respond. What are those top citations that we are actually issuing out the top 25? From our state agencies accreditation organizations and also with CMS and knowing that we can actually then move over into looking at our stakeholder engagement and being able to better clarify our compliance assessments. And the next thing we're also looking at. Would be data we're conducting a data driven challenge. So actually, how do we increase a clinical laboratory excellence through the data that we actually have, and using that as a purposeful meaning, to actually come back in and analyze our overall program? And so, having this data driven method-- as we come back in for these analyses of where have-- where do we have areas of noncompliance at? and how do we address these areas of noncompliance? And then the next thing would be also, how do we work with our partners to increase the educational assistance arm of working with them for these areas of noncompliance? And then still coming back from these areas of non-compliance. What regulatory updates and challenges will we have that we need to actually address and prioritize? So, through this reorganization, you can see that we have a lot of work that we're setting forth for ourselves over the next two years. And really just engaging our stakeholders and our partners, looking at our data, looking at consistency, and really just coming together collectively and analyzing the CLIA program. Can I have the next slide also? And here, you can find that we have our lab excellence mailbox. We get inquiries on a daily basis. Within a policy branch, individuals are actively, on a daily basis, answering questions. And this is one of the things that I mentioned earlier. From this mailbox, that we can move forward with actually collecting information, we also have various COVID questions that come in. And we'll be forming analysis of those questions and going back in there and just really looking at the lessons learned long time from our COVID response. What inquiries did we have? What can we do better with the next public health emergency? And even in the middle of this public health emergency, how do we respond better? And so from these questions that we're setting forth, how do we engage our stakeholders, and what do we know that's happening within a public health community itself and within our laboratory community, so we can actually serve better with our partners, stakeholders, overall, and the laboratory community? And a last word is, how do we actually increase excellence of laboratory quality overall? And so, I was not actually at CMS through this whole response. But the entire team was there. And they've worked extremely hard. So, I want to thank the entire team for their efforts and for all of our partners and stakeholders that have worked with us over this time period in responding over the last year. Because when you have nearly 300,000 laboratories that we're actually working with and having oversight over-- and just having our enforcement arm-- and then we're actually back out surveying. And we're just responding to several complaints that we have. And looking at COVID as a whole and making sure that individuals know how to be CLIA certified and move on to the next step. And those individuals-- those laboratories or facilities that are not CLIA certified-- just bringing them aboard and teaching them about the lab excellence and quality that CLIA actually has to offer. And thank you. CLIAC CHAIR: Thank you, Miss Spruill. It is breathtaking just to think about what you did in that one year. We thought we were buried, but I can sense you were buried, much as Dr. Fitzgerald was buried. So, thank you, thank you, thank you. Before we move on, Steve Hinrichs is back. And we would love to have you introduce yourself and declare your conflicts of interest. DR. STEVE HINRICHS: Very good. Sorry for the technical problems. My university IT security system kept kicking me out. But anyway, I am back and hope to be able to continue. My name is Steve Hinrichs. I'm the chair of the Department of Pathology and Microbiology at the University Nebraska Medical Center. And I am one of the outgoing members of the CLIA committee. It's been my pleasure to be on the committee for a number of years. And I'm sorry that we aren't able to be together in person. But I also want to thank Valerie and Ren for all the support they provided over the year. I have no conflicts, thank you. CLIAC CHAIR: Thank you, Steve. Moving on. We know CDC and CMS were part of the storm we all faced last year. But we definitely know the FDA was right in the middle of it. So, we're going to turn it over to Tim for your update. Dr. Stenzel.

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Food and Drug Administration (FDA) Update Timothy Stenzel, MD, PhD, FDA EX OFFICIO DR. TIM STENZEL: Thank you, Valerie. That's absolutely true. Next slide, please. And we're still working very, very hard to increase testing opportunities. We are focused, now, on those, which is different than the beginning of the pandemic. We're focusing on those opportunities that can greatly expand access. And I'll go into some of those in this talk and in subsequent talks during this CLIAC meeting. We continue to work with developers of all sorts and kinds in order to make more tests-- and accurate tests-- available to more people. Next slide, please. So here is just a few key milestones in the past more than a year. We began our efforts at the FDA in early January. And the first authorization was early February with the CDC assay. The first screening authorization-- so this is a situation where, when we examine data in asymptomatic patients, and the data was sufficient to support authorization for that screening claim, and that was in July 2020. And as we know, screening of asymptomatic folks has become even more important now. And we now have authorized well over 20 tests to be screening authorizations. And we have made it abundantly clear that unless there's a prohibition in an authorization of an e-way authorized test, we support-- we don't object to off label prescription of screening testing by clinicians. And-- but we do really support the opportunity to authorize screening tests. Also-- and I think you can still hear me-- my Zoom just went out, so you may not be able to see me. In December, we authorized, along these lines of increasing access, the first home collection and the first home test. And this is OT-- both of these were OTC-- over the counter-- meaning that no prescription was needed in order to receive this test. It means that consumers could reach out and order the test. And so, this is just the continued evolution of the technology. It must automatically mute me when I come in. Hopefully, you caught most of what I said up until when you mentioned that I was muted. But now, we have over the counter tests, both in-home tests and home collection. We have I think well over 50 home collections now, and a growing list of over the counter tests. And then more recently, as I said earlier, we really support authorization for screening for EUA authorized tests. And we opened up a new guidance and a new pathway. For tests that showed at least a floor of performance in symptomatic patients of at least 80% sensitivity, with a lower bound of 70%-- that if they agreed to conduct testing in a serial fashion-- at least weekly for molecular, at least twice a week for antigen test-- then we would authorize them for asymptomatic screening with the condition of authorization that they would perform a post authorization, post-market study to prove that their serial testing program, and those that they serially tested, presented adequate performance for safety reasons. Next slide, please. This slide highlights, just since November, some firsts. And there have been an enormous number of firsts since the beginning of the pandemic. And I've previously spoken in other forums about those. This is just to show that these firsts are still coming along fast and furious. And we're still seeing them. And they're still important. These new technologies and the new offerings are still very important in managing the pandemic today. So, we authorized the first neutralizing antibody tests. We authorized the first health testing at home with Lucira. That's a molecular test. That's the first home molecular test-- first that we've authorized as an agency. The first combo test-- of not just COVID but flu, and then subsequently other analytes of importance-- and of course, these combo tests are important when there is the possibility-- and even today, a lot of patients who are tested for COVID who have symptoms have something else. And it's always nice to know, if they don't have COVID, what do they have to explain the symptoms, as there are false negatives with COVID testing? And when you have a positive for flu-- which is, fortunately, in very low abundance right now, for an RSV or others-- then you know what the cause of those symptoms is and you can take care of that patient appropriately. As I mentioned earlier in the previous slide, the first direct to consumer. We distinguish direct to consumer and over the counter in this. Over the counter is-- we reserve for in-home testing or non-laboratory testing. Direct to consumer is for a collection kit. So, we just kind of make that distinction. We make it very clear internally and externally when we're making these authorizations, what does it mean. We authorized the first NGS test, to aid and adapt to T cell immunity assessment. So, more and more body of work is demonstrating that, actually, the immunoglobulin and neutralizing antibody generation is not necessarily what's driving immunity, especially following vaccines. But it's T cell immunity. And this is hopefully the first of a number of T cell immune response tests that we will receive and be able to authorize. As I mentioned, we had the first molecular nonprescription, at home tests and the first authorizations for this new serial testing screening program. We now have well over six-- maybe we have eight. I forget. But we're constantly updating those authorizations, as we are across the board for those types of tests that can impact the public health response and clinical efforts in the community and across the health system. Next slide, please. So, this is just a pictorial bar graph showing the continued growth and EUA authorizations. Either in this talk or a subsequent talk I'll talk about the various guidances that we've issued through the pandemic. So, these are just the e-way-authorized tests for diagnostic, which is molecular, antigen, and serology tests. We have made many, many more available through the notification path. And I'll speak to that later. Next slide, please.

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So, this is a high-level view of the types and breadth and depth of assays that we have authorized. We're up to an incredible amount of innovation, obviously, because we didn't have a single test on the market when the pandemic began, that occurred that was authorized that could detect SARS-CoV-2. Pooling has been, obviously, for molecular tests has been a big boon to be able to screen large numbers of patients, including those at schools and workplaces. I talked about the asymptomatic screening authorization. It's a multi analyte of flu, RSV, other analytes-- some of them large panels-- plus SARS-CoV-2. Point of care molecular tests, home collection-- those-- home collections are continuing to be a very robust development area. And we continue to authorize those on a weekly, if not daily, basis, if you watched our recent authorizations. We've had the first home collection multi analyte test. And so, we're not just looking in the home for SARS-CoV-2, but also anything else. Of course, the home collection-- home test-- situation has advantages in a number of ways. One, it relieves pressure on health care systems to do the collection, and/or testing and shipping. These are all set up-- it's their home collection with shipping to central labs for testing, and have been demonstrated to be stable, so that we know that accurate results are obtained. It's truly amazing to me that patients at home can collect a molecular test and an antigen test sample and get accurate results. So I think this is really opening up our thinking for what can be done outside of traditional health care settings, and not just in this pandemic, but for every other analyte where that makes sense, including other respiratory viruses and non-respiratory testing. Saliva is a very surprising analyte that can be used in COVID testing. This remains somewhat controversial, I will say, in my mind. There's a recent study published that was supported by NIH and the RADx team, that is showing clearly lower viral load in saliva, even lower than what can be detected in viral culture for SARS-CoV-2. So, we are continuing to take a very close look at saliva. We know there are times a person is an easy sample to collect. We know there are times when swabs have been in short supply, and saliva provided a needed alternative to swab-based testing. For antigen tests, as we look at the of development of technologies, antigen came last. First, molecular, then serology, and then antigen test. That's largely because of the ability and the time it takes to develop the building blocks for these tests. So, for molecular tests, you can often-- you can get primaries and probes pretty quickly after you order them. And the technology is relatively robust, well known in PCR. And you can put together a test in fairly short order once you have sequence information for the target. For serology tests, you simply need to produce largely an antigen and have one that can be used in the serology test. And then that's the only component you switch out, primarily, from other tests. You've got to work out the particulars of that. And there can be some fine tuning of the performance so that you have good sensitivity and specificity-- particularly specificity. But we saw a lot serology tests come into the market relatively early in the pandemic. Antigen tests require the development of antibodies. Now some of them, early on, used antibodies developed to SARS that was seen well over a decade ago. And antibodies were developed and used. And of course, those antibodies that were generated are not going to be able to distinguish SARS-CoV-2 from perhaps other SARS. But since SARS-CoV-2 is the only circulating SARS right now, the specificity is good in clinical testing. And yet, others have developed their own antibodies. But also, the technology itself, in order to make it sensitive enough to be used in a reliable way, does take a lot more work to develop an antigen test, even when you have antibodies that have been developed. And so far, as I've stated, we've authorized a number of antigen tests for asymptomatic screening. And that's key, when you try to get millions and millions of test results a day, which is well above what our nation is currently producing at Central Labs right now. And then serology is interesting because I think there were a lot of high hopes in the beginning of the pandemic that serology could be very, very useful. I think that has been tempered by reality and perhaps not surprising. In prior pandemics, serology has not played a major role in testing. And yet, there's continued interest. Of course, there's donor selection for convalescent plasma donation. There is the thought that perhaps we can use these for determining, say, responsiveness to vaccines, surrogates for immunity. I think there's a lot of work that needs to be done before serology tests can move into that sphere of measuring any sort of immunity. And then, of course, I mentioned that there are a lot of tests that haven't yet been authorized but were notified. And this was a pathway that we opened up at the end of February of 2020, at first for laboratory developed tests-- that they could let the FDA know that they had validated their tests-- notify us-- and then have a certain number of business days to submit the EUA for our review. And all the while, we were conducting that review, we would allow that test to be marketed. And that was a very welcome flexibility on the part of the FDA to allow a lot of tests to quickly enter the market after that decision. And then, of course, we updated it on March 16th of 2020, to allow-- molecular tests were developed as kits along that same pathway. Next slide, please. And as we have seen evolution of authorizations through the pandemic, we have now authorized the first full authorization for SARS-CoV-2. And this is on one of the BioFire panels. With granting of the de novo-- and this will, in large part, be the only de novo required for any molecular SARS-CoV-2 test, whether it's a panel or not, because we have decided that we can write special controls, which are required for de novo application, that will apply, essentially, to most if not all molecular assays in development. That means all subsequent molecular tests that come in for EUA authorization-- I mean for full authorization-- can follow the 510(k) pathway, which is the easiest full authorization pathway available to diagnostic tests. With the granting of this de novo, by law, the FDA does revoke the original EUA for this device. It's no longer needed. However, we've received multiple questions-- multiple concerns-- about whether EUA tests will still be offered now that we have authorized the first molecular-- fully authorized the first molecular test. And the answer is yes. We are not going to pull EUAs off the market, simply because we have authorized-- fully authorized the first one. I mean, this

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makes a lot of sense. There is a huge need for testing. BioFire a great platform. So, we wouldn't have authorized it if not. But it just doesn't have the workflow and the volume to support all of the nation's molecular testing needs. We have repeated that multiple times, that with this EUA ratification and de novo authorization does not impact the availability of other tests that have been EUA authorized. And nor are we stopping to review tests and make EUA authorizations. So, I just want to very clearly state that for all. That's our intention right now. There may come a time when the emergency is no longer declared. That's unlikely to happen any time soon, as we still have declared emergencies, say for Zika and Ebola. And we still have EUA authorized tests for both those pathogens. So, we don't see this being an issue. Should it be an issue, we have drafted guidance that will have a period of time when the emergency is no longer declared and tell EUA test holders can come in for a full authorization. This will be a sufficient time for developers to make the conversion to full authorization. And as soon as that guidance is cleared by all the clearance needed for guidance, we will make that guidance publicly available. Next slide, please. So, one key area of much interest and real concern is the impact of viral mutations and variants, obviously, not just on testing, but also therapeutics and vaccines. Since the very beginning of the pandemic, we have asked EUA developers-- especially molecular developers-- to do an in-silico analysis to make sure that their primaries and probes can detect the circulating viruses that we are aware of. And we do this by looking at sequenced databases. And that has been very effective. In early summer 2020, we-- because we had freely authorized tests, we had all primaries and sequences-- internally, at the FDA, we began searching the database-- sequence database-- for any mutations that were a significant percentage in the population that could impact, overall, the test performance. We set a threshold for those sort of normal circulating variants of 5%. Anything 5% above could potentially decrease sensitivity by 5% or more, as a current-- as that threshold at that time. And then subsequently, we have now taken into account the variants of import-- particularly UK, South African, Brazilian and others-- and determine whether or not tests were impacted. That's been ongoing, as I said, from the beginning with each EUA authorization. It's been ongoing on a regular surveillance basis by the FDA since early summer 2020. And we have now stepped it up more recently. We've made public some information. Out of abundance of caution, we've made available to all that there were four tests that were potentially impacted by variants and mutations. And however, fortunately, we don't think any are significantly impacted. It was out of abundance of caution that we made this information available. We now have a website that will keep the community updated as to the impact of specific mutations and variants are that-- where we think there's a potential impact. And again, we will use the abundance of caution-- a tool-- to make this known, even if we may not think that there is a significant impact on testing performance. And then more recently, we issued, on February 22nd, guidance to product developers to bring them into the ongoing monitor situation and extend beyond, with the FDA and other authorities are doing to monitor this situation and engage test developers in their own ongoing, to extend it, obviously, into antigen tests and serology tests, as well. And so, we have now engaged hundreds of test developers on this topic. And it has been a very good and robust dialogue. And we'll continue our efforts in here. Obviously, there's potential concerns. They're not just molecular test performance, but also antigen test performance. And we are working on ways to improve our monitoring of that, as well. Next slide, please. So, we have engaged the public and test developers in really unprecedented ways during this pandemic. I personally, mostly, hosted these 50 virtual town halls-- I missed the one today, because of the CLIAC meeting-- and engaged a number of callers over those 50 virtual town halls-- almost 40,000. And we have-- transcripts are available online of all those. And we try to post those as quickly as possible after a call, because tech developers and others use that information to help them in their development efforts. We have provided an unprecedented number of FAQs on the FDA website. Really, truly a standing effort on safety communications. Whenever we find a test may be impacted by anything, or have an issue on market, where we've confirmed it and it passes the threshold of a potential significant, or out of an abundance of concern-- we make those communications available to our safety coms network. We've provided resources to patients, health care providers, and developers. We have maintained an email box, now with more than 185,000 inquiries. We respond to those very quickly. That team that monitors those have done an excellent job since the beginning of the pandemic. And they've had other topical calls and guidances, as well. Next slide, please. It's not showing up in my screen. But it's probably showing up on yours, yeah? So, Jeff Shuren and I have published a number of articles and pieces and blogs since the beginning of the pandemic. And this is one of the recent ones in the Health Affairs blog on March 22. And it really talks about increasing access and ensuring reliability of tests now and in the future. It incorporates lessons learned in this pandemic. We believe the US government should invest in the development of truly novel technologies. We've been very involved with RADx since the very beginning. I personally speak to RADx teams twice a week since, I think, June and July of 2020. We believe that the US government should equip non-laboratory and providers and consumers with tools to help understand testing. And as we expand into the home users and the non-professional testers, this will be ever more important. But we have seen hiccups in the launch of tests because of a lack of understanding of test performance. We think investing in point of care and home test technologies now will allow rapid expansion in national capacity, and these same types of tests can be applied to other non-SARS tests going forward. So, this is a great effort to support. The wide availability of point of care and home tests has created a wealth of data, if we can get that data. And so, we recommend that we develop robust reporting for these. And finally, reimbursement has been an issue for some areas, and CMS-- I'm not throwing CMS under the bus here at all. They are tied to legislation and

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what they can do, but certain things like home tests, over the counter tests, pool testing, and screening tests have represented reimbursement challenges. Next slide, please. And we have not been just focused on SARS, and I just wanted to throw this in here to show that we are still reviewing all the non-SARS applications, and we are looking at access to other types of tests. So, this was a big authorization, the first CLIA waivedr, to a community gonorrhea test. And we hope to see many more, not just, obviously, from our SARS test, but also sexually transmitted diseases and others, and actually in the home testing for sexually transmitted diseases, molecular, and other types of testing. Next slide, please. So, the next topic is a little bit further afield, and we are currently in what's called MDUFA 4. This is the Medical Device User Fee Amendments. In 2007 it was attached to the FDA Reauthorization Acts, or otherwise called FDARA. These are our key focuses for the next MDUFA, which is currently being discussed, and we want to look to an innovation engagement with all stakeholders. We want to improve safety through the TPLC. TPLC stands for the Total Product Lifecycle. This means, from the various earliest contacts that the FDA has with developers, they may have a concept. It might be through the breakthrough program that we administer, all the way through launch and monitoring those test performance and device safety performances on market. And we want to continue to look at how we structure the FDA and staff it and resource it to keep pace with the innovations that we're seeing, and some of them have explained on SARS. Next slide, please, and this is my last slide. This is the key feedback that we've received from stakeholders going into the MDUFA 5 period. Folks want to engage with us more, and we welcome that. Folks want to use-- developers want to use real world evidence to support regulatory decisions. We've already been using it. We want to greatly expand that, and we have programs in place to do that. There's an increased focus on device safety. This would require an enhanced plus market surveillance system. There's been a lot of interest, and obviously the FDA has made authorizations in the digital health space, and there's a lot of excitement about what digital health can do to better treat and take care of patients and better monitor their health. So, patients are an ever-increasing part of our reviews, and integrating patient experience data into the regulatory decision-making processes is excellent. And we've been doing this in the diabetes area, and we look to expand that into other areas as well. The diversity in patient engagement is important, as well as in clinical trials and real-world evidence. We want to incentivize innovation for underserved populations, and we want to expand early payer feedback program. And this is aimed at making sure that, once we authorize a novel test and other devices, that there's actually a reimbursement situation in place that can support the use of those devices. And thank you very much. CLIAC CHAIR: Thank you very much, Dr. Stenzel. It was exhausting to watch your recap the past year, and it is so encouraging to see how the lessons we learned could dictate our path forward. Thank you so much. Our next presentation is a CLIAC recommendations update from Ms. Heather Stang and Dr. Lisa Kalman. Ladies, the floor is yours.

CLIAC Recommendations Update Heather Stang, MS, MT and Lisa Kalman, PhD MS. HEATHER STANG: Thank you, everyone. Turns out I would have problems showing my own slides. [LAUGHS] I've been so focused on everyone else's. So, I'm going to give you the first part of this follow-up on CLIA recommendations. You may recall that, during the November 2019 meeting, Ms. Nancy Anderson provided an update on CLIAC recommendations from the November 2018 and April 2019 meetings. I'm going to follow up on several exciting activities that we've been participating in that's related to the April 2019 next generation sequencing CLIAC recommendations. First, I want to remind you that we have a table that contains all of the CLIA recommendations on our CLIAC meeting website. So, on the left panel, you'll see a little tab that says Meeting. If you click on that, it will open the screen. You're going to scroll down to where it says CLIAC Recommendations. And in the box, there, you're going to see the file that will list all of the CLIAC recommendations in the table format. After each meeting and before the next CLIAC meeting, we update that table with the current recommendations. In that table, you can look up every recommendation and their status going back to 1992. This table includes links to letters that have been sent to HHS and other relevant information. Since 1992 when CLIAC was first chartered, there has been 161 formal recommendations made. We track these and include these totals in our annual report to the HHS secretary. For the fiscal year 2020 report, approximately 83% of these recommendations have been fully implemented. The remainder 17% have been, to some degree, partially implemented. I want to also give you another reminder that the information that the committee provides to develop these recommendations is considered advice to the government. And while the government is not required to follow up on every single recommendation, these recommendations significantly influence the work that we do, and we rely on these recommendations for helping to guide us as we move ahead in our activities. Before I move on, I wanted to provide a brief reminder that during the April 2019 CLIAC meeting, there were

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reports provided from the three CLIAC work groups, the CLIA personnel regulation work group, the non-traditional testing workflow model work group, and the next generation sequencing work group. There were eight recommendations made at that meeting related to the formation of a new CLIAC work group and next generation sequencing activities. During the April 2019 CLIAC meeting, a recommendation was made to update the CLIA regulations to address issues related to biomarker testing and other new technologies. This update could include a new section, a revision of existing sections, or other alternatives. And the update should take into account the reports that were provided by the CLIA personnel regulations work group, non-traditional workflow models work group, and NTS work groups. Also, another recommendation was made to create a new CLIAC work group with the charge of determining exactly how those updates are going to be made and integrating the findings of the three work reports. The planning for the new CLIA regulations assessment work group was paused to allow the agencies to focus on the pandemic. CDC, CMS, and FDA are now actively engaged in the formation of this new work group that will include representation from clinical and anatomic pathology laboratories, public health laboratories, laboratory accreditation organizations, point of care testing sites, CLIA-exempt states, industry, and other experts from the previous three work groups. The theme of this work group will be the total testing process evaluation, and the topics will include remote pathology after the pandemic, digital pathology, analytical testing specifications, distributed testing and the non-traditional workflow model, and data as a specimen. Another focus of this work group will relate to the oversight of CLIA certificate of waivedr and certificate of provider performed microscopy procedures laboratories. The information provided in the three work group reports, along with the November 2019 CLIAC public comments section and tomorrow's session on the expansion of point of care testing, self-collection, and self-testing, will provide insight to the agencies for the development of a series of questions for the work group to address. We will be assembling the work group roster and sending out invitations to potential work group members early this summer with an anticipated virtual meeting mid to late summer. There were two CLIAC recommendations for surveys or information gathering from organizations performing next generation sequencing to collect data on bioinformaticians and to define specific use cases for long-term storage of NGS data, and for keeping archival software, hardware, and platforms. To address these recommendations, CDC obtained comment through a request for information published in the Federal Register in May 2020. The request for information included five questions aimed to gather feedback at the current state, challenges and practices relevant to personnel performing bioinformatic activity in clinical and public health laboratories, storage and retention of next generation sequencing data files, and maintenance of sequencing analysis software. CDC received 16 responses from that first set of respondents that included reference laboratories, public health laboratories, academic and clinical laboratories, professional societies, industry, and private citizens. Responses received were helpful in identifying several issues relevant to personnel and the retention of next generation sequencing data in clinical and public health laboratories. The CDC Division of Laboratory Systems' next generation sequencing team has completed the review of the public comments and developed a summary report. The report will inform federal activities relevant to the questions posed within the request for information, provide information for work group discussion areas, and the report will be presented to CLIAC during a future meeting for CLIAC deliberation and possible recommendations about future changes to the CLIAC regulations. CLIAC also made two recommendations about guidelines or guidance documents that should be developed by the government and professional organizations related to next generation sequencing. The Next Generation Sequencing Best Practices Forum will bring together organizations that are involved in writing guidelines or best practices on NGS. The forum will provide an opportunity for open discussion to gauge the activity of each organization for next-generation sequencing and to determine whether the agencies can assist or lead the charge in filling the gaps or addressing the challenges with guideline development and implementation in clinical laboratories. This forum will include a series of virtual webinars. During the first meeting on April 20 next week, CDC will provide an overview of a next-generation sequencing adapt a total testing process diagram, which will be used as a reference for future forum presentations. This presentation will then be followed by an overview of the CDC APHL of next generation sequencing quality initiative, with a period of time devoted to participant questions and open discussion. For the remainder of the sessions, we will invite participation organizations to share their accomplishments, priorities, and challenges, as well as experiences with NGS guidelines, best practices, and tools developments. There will be a period after each presentation for open group discussion. Presentations from each forum session will be provided on a new CDC live quality molecular methods web page. During the November 2019 CLIAC meeting, Dr. Fitzgerald provided an introduction to the NGS quality initiative. The CDC, the Association for Public Health Laboratories, state and local public health laboratory partners are collaborating to harmonize quality standards for next generation sequencing across public health. The NGS quality initiative is moving forward a coordinated and comprehensive plan to develop and implement in the next-generation sequencing-focused Quality Management System, or QMS, to ensure high quality, reliable data for nationwide disease surveillance systems, diagnostic or reference laboratory testing, and other public health actions which improve patient care and public health outcomes. To support the laboratory in building a foundation of quality and as a development and implementation of NGS-

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based tests, the initiative's quality management system is organized and prioritized using the 12 Quality System Essentials, or QSEs, within the Clinical and Laboratory Standards Institute Quality Framework book. We view the regulations and standards such as CLIA, FDA, CAP, and ISO-- they're applicable to NGS, but we see our NGS quality initiative QMS as the foundation. We have developed products and tools related to eight of the QSEs. We are currently working on and have products in various stages of development for the remaining four that include organization, customer focused, purchasing and inventory, and nonconforming event management. Once complete, the NGS quality initiative will provide a foundational QMS toolkit for CDC and public health laboratories and provide a platform for knowledge and information sharing. The NGS quality initiative formed, and is actually partnering, with the joint public health laboratory and CDC Technical Coordinating Committee, or TCC. This committee includes CDC staff and public health laboratory members. Expertise consists of laboratory scientists, bioinformaticians, and quality managers. The TCC has several subgroups, and each subgroup is assigned products for each QSE and collaboratively work to develop the document and tools following our standard product requirements. Bench level professionals, bioinformaticians, quality managers, and laboratory leaders can currently access over 80 customizable, ready to implement products, which include guidance documents, SOPs that forms. To best meet the need of the sequencing community using initiative products, we are currently developing short instructional videos that will help users on-board and utilize some of these tools. The first set of videos that we will be providing on our website by May will assist laboratories in on boarding our new inventory management tool. As the NGS quality initiative works towards completing its foundational QMS, we anticipate surpassing over 100 products on the web page by this fall. To help users quickly identify these products that they may be interested in, as well as any supporting materials that may be related, we are working to add a series of filtering options to our current website. Laboratories can adopt these free QMS tools and resources to support training and personnel, helping them choose the appropriate protocols and analytic options, and implement effective management and process controls. Such tools are especially beneficial to laboratories performing NGS-based based tests and are subject to meetings the CLIA regulations and other laboratory accreditation standards. Products from this initiative can serve as a foundational QMS or complement existing resources and support the expansion of a laboratory's current QMS. If you'd like more information on this product or if you have any questions, you can check on our website, or you can email us at NGSquality@CDC.gov. I will now turn it over to Dr. Lisa Kalman to provide an update on the electronic reference materials for next generation sequencing. DR. LISA KALMAN: Hi. Thanks, Heather. Can I have the next slide, please? OK, so clinical laboratories use reference materials for a variety of their needs, including developing and validating new genetic tests, and also for quality control and proficiency testing. Although reference materials are critical for laboratory testing, there are no characterized and publicly available reference materials for the majority of genes that are currently tested in clinical genetic testing labs. To address this situation, in 2004, the CDC created the Genetic Testing Reference Material Program or GeT-RM. The GeT-RM is a collaborative CDC-based program designed to improve the availability of reference materials for genetic testing. This program works with a variety of partners, including government agencies, cell repositories, patient advocacy groups, professional organizations, IBD manufacturers, and clinical genetic testing labs. All the partners work together to identify reference material needs for genetic testing and to create publicly available, renewable, and characterized genomic DNA reference materials. A one-page description of the GeT-RM program and a list of our 13 current publications is provided in the meeting materials. Next slide, please. Since 2004, the GeT-RM program has characterized a variety of genomic DNA reference materials, including materials for Fragile X, Huntington's disease, cystic fibrosis, nine disorders on the Ashkenazi Jewish panel, a lot of different pharmaco genes covering three different [AUDIO OUT] projects, Duchenne's muscular dystrophy, myotonic dystrophy, Rett syndrome, 11 HLA, and most recently, for spinal muscular atrophy. All of these genomic DNA samples that were characterized by GeT-RM projects are renewable resources and are publicly available from the Coreal Institute for Medical Research. Can I have the next slide, please? Next slide. As Heather mentioned, at the April 2019 CLIAC meeting, the committee presented a variety of recommendations to the CDC, FDA, and CMS to help assure the quality of clinical next generation sequencing. And this was based on the input of a CLIAC work group. A summary of the meeting is available. And I have the URL on this slide. Can I have the next slide, please? So, recommendation number six concerns the GeT-RM program. And in this recommendation, CLIAC recommended expanding the GeT-RM program with regard to its scope and the type of samples that it works on. The committee suggested that the expansion could also include the creation and the curation of next generation sequencing data sets to be used by laboratories when validating or revalidating their bioinformatic pipelines. Can I have the next slide, please?

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So, the GeT-RM program is working to address this recommendation, and we're doing a project that will be done in two stages. In the first stage we're developing a list of expertly curated and clinically important variants that can be used when creating multi-variant electronic reference materials by "in silico mutagenesis," and I have that in quotes, of laboratory-generated next generation sequence files. In the second part of the project, we're going to create and pilot test electronic reference materials. Can I have the next slide, please? So, in the first part of the project, we developed a collaboration with the ClinGen project, including its variant curation expert panels, a group of clinical laboratory directors, and a CAP committee member. As part of this collaboration, we approached 36 of the ClinGen variant curation expert panels. And these expert panels are basically a set of experts on a particular gene or set of genes related to certain disorders. And so, they're very well familiar with these genes and know all the ins and outs of testing for them and all the important variants. So, we went to these groups and asked them to nominate very important pathogenic variants in their genes of expertise, as well as variants in these genes that would be difficult for clinical laboratories to detect by next generation sequencing. We received 546 variant nominations that cover 84 disease genes associated with common genetic disorders, and these nominated variants included common pathogenic variants, as well as variants that are difficult to detect. We received multiple types of variants, multiple variant types, including 346 single-nucleotide variants, 104 deletions, 37 copy number variants, 25 gene duplications, 18 deletion insertion, five inversions, four insertions, and two complex rearrangements and two fusions. Can I have the next slide, please? So, once we received the nominated variants, the variant descriptions, nomenclature, and disease associations were further curated and refined by the ClinGen staff. This curated list of variants will be posted on the GeT-RM and ClinGen websites, and we are currently preparing a publication. And we hope that in the future, we will solicit nominations for additional genes and variants that will be added to our list to increase its usefulness. Now can I have the next slide, please? So in the second part of the project, we hope to do a pilot to demonstrate how the curated variants from the ClinGen GeT-RM variant project could be used to create reference materials by adding them in silico into next generation sequencing files. The pilot will examine whether the variants that are added into the next generation sequencing files can then be detected by clinical laboratories, and we hope that our pilots will also demonstrate a general process that laboratories can use in order to develop their own electronic reference materials that meet their own assay needs and also to encourage the use of electronic reference materials by clinical laboratories. And can I have the next slide, please? So, what we decided to do was we selected 50 variants from our ClinGen GeT-RM project list that are in 21 genes related to cardiomyopathy and heritable cancer. These are genes that are very often tested by clinical laboratories. Seven clinical laboratories volunteered as part of our pilot study, and they generated next generation sequencing files using their normal assays that they normally use in their laboratories for heritable cancer and cardiomyopathy. And they did this by sequencing a publicly available genomic DNA sample. The next generation sequencing files from each of the laboratories were then transferred to a company who electronically adds the 50 variants that we selected into the sequencing files from each laboratory. And this is where the project stands right now. Can I have the next slide? In the future, we will return the mutagenized files back to the laboratory that they originally came from, and the laboratory will analyze the files using their normal bioinformatics pipeline and report the variants that they detect. The laboratories will know which genes are included in our study but will not know the variants that have been added to their files. We will look at the variants reported by each laboratory to assess how well the reference materials worked and compare across laboratories. And we will prepare a manuscript describing this study, as well as the general process that laboratories could use to create in silico reference materials, probably using the variants that we have identified from the ClinGen part of the project, as well as other variants, as well as documenting the feasibility of using and creating in silico reference materials. Can I have the next slide, please? So, this slide shows the participants from both studies. On the left, we have the people and organizations that participated in the ClinGen variant project, and on the right, the participants who helped plan the pilot project as well as the seven laboratories that are participating. Thank you very much. CLIAC CHAIR: Wow, thank you very much, Dr. Kalman and Ms. Stang. So much work. April 2019, CLIAC weighed in. Look how far we've gone. Even including 2020 was a giveaway. Right. From our perspective, nothing could happen. Our next and final talk of this session is from Dr. Julie Villanueva on the Laboratory Response Network. Dr. Villanueva.

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Laboratory Response Network (LRN) Overview Julie Villanueva, PhD DR. JULIE VILLANUEVA: Thank you for inviting me. Today, I'd like to give an overview of the Laboratory Response Network and talk a little bit about response to biological threats. My position at CDC, I'm the chief of the Laboratory Preparedness and Response branch in the Division of Preparedness and Working Infection. Next slide, please. This just briefly describes the topics that I'll cover. I'll give a brief background of the LRN and then talk about detecting biological threats as well as emerging infectious diseases, and then talk a little bit about our current capabilities and our challenges, and some of our future work. Next slide, please. Next slide. Thank you. So, the LRN was established in accordance with the Presidential Decision Directive 39, and that outlined national anti-terrorism policies, and it assigned specific missions to different federal departments and agencies. And so, through a collaborative effort with our two other founding partners, the Federal Bureau of Investigation and APHL, the LRN became operational in August of 1999. And its objective was to ensure an effective laboratory response to bioterrorism by helping to improve the nation's public health laboratory infrastructure. And so, the LRN is formally incorporated into the national response framework, and the national health security strategy, and most recently, the national bio-defense strategy of 2018. Next slide, please. The mission of the LRN is to provide rapid laboratory response to biological and chemical threats, and to inform critical decisions about public health and safety. And so, over the past 22 years, the LRN has expanded testing capacity for biological, chemical, and emerging public health threats. By providing critical funding to states, the CDC helps to ensure that state and local public health laboratories meet strict bio-safety standards, acquire state of the art testing equipment, share electronic results securely, and can retain qualified, trained laboratory personnel. Next slide, please. So today the LRN is charged with the task of maintaining this integrated network of sentinel, state, and local public health, federal, military laboratories that can respond to biological and chemical threats as well as other public health emergencies. And as you can see from this slide, the LRN is comprised of both biological and chemical components. The LRNB oversees the detection of biological threats, including bio-terrorism agents and emerging infectious diseases, and this is the area in which I'm going to focus mostly today. But first I'd like to talk briefly about the LRNC, which is also overseen by the CDC. Next slide, please. So, for the detection and characterization of chemical threats, the LRNC operates in a system of tiered laboratories. Some of these laboratories are limited in their technical capabilities to proper collection and shipping of clinical samples, and these are the level three laboratories. The level one and level two laboratories can perform testing for a broad array of chemical agents to cyanide and industrial chemicals. The level one laboratories can also test for chemical nerve agents. And the CDC itself serves as an international reference laboratory for the testing and characterization of chemical agents. There are more than 50 state and local public health laboratories that can provide testing on clinical samples to measure human exposure and toxic chemicals. Next slide, please. So now I'd like to go into more detail about the LRNB. So, our first tier are the sentinel laboratories, and these are clinical laboratories that are often located within hospitals that really provide the first line of defense against biological and chemical threats and emerging infections. These trained laboratorians can quickly rule out and refer suspect threats to LRN reference laboratories for confirmatory testing. There are thousands of highly trained clinical staff that form the bedrock of our nation's response capabilities, alerting public health experts to unusual findings. Again, as I said, the sentinel laboratories are truly our first line of detection in the LRN. And having technical capability to rule out infection with common pathogens and then recognizing that infection could be caused by something that's uncommon, and then collaborating with the LRN reference laboratories, which I'll discuss next, are absolutely critical steps of the process when we're detecting something novel or a bio-threat. Next slide. So, this is the second tier of laboratories. These are LRN reference laboratories, and sometimes they're called LRN member laboratories, and they're responsible for investigation, and testing, and referral of specimens and samples. So, there's more than 120 domestic state and local public health, military, veterinary, agriculture, food, and water testing laboratories that comprise the reference laboratories. And CDC provides these LRN reference laboratories with reagents, protocols, and specialized training so their staff can perform testing on multiple agents on high-risk environmental or clinical samples. The reference laboratories also provide training and guidance to thousands of sentinel laboratories across the United States. And I'll talk a little bit about that in future slides. Next slide, please. So, this map just shows the distribution of LRN reference laboratories across the United States. Every state has an LRN reference laboratory, and many states have several, as you can see from the map. Approximately 84% of the US

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population lives within 100 miles of an LRN reference laboratory, which will hopefully expedite timing of shipping and results. Next slide, please. So, I mentioned earlier that the LRN sentinel and reference laboratories have very strong collaboration, and it's incredibly important. Each state receives funding through the Public Health Emergency Preparedness Cooperative Agreement, and that helps to support training to detect these anomalies. The existing network within each state is managed differently, and that fosters this very important collaborative effort. The American Society for Microbiology and Association of Public Health Laboratories are two important LRN partners that help contribute to this. They provide great resources and information to sentinel laboratories, such as the link that I provided. Next slide, please. So, the final tier of our structure includes our LRN national laboratories, which includes the CDC, the United States Army Medical Research Institute of Infectious Diseases, and the Naval Medical Research Center. And these laboratories are responsible for specialized characterization of organisms, bio-forensics, like agent activities, including research and development of diagnostic tests and handling highly infectious biological agents. Next slide, please. This is a list of our LRN partners, and I have to say that it's so critical for these partnerships. The LRN is a partnership between government, private organizations that have a stake in biological and chemical preparedness. And the success of our network is highly reliant on these partners with whom we work. CDC oversees this LRN program but have input and recommendations provided by many agencies and organizations. Next slide, please. OK, now I want to move into detecting biological threats. So, the LRN is a unique collaboration between law enforcement and public health. The FBI brings its forensics expertise and requirements to this program, and there's a partnership between public health and law enforcement is a prerequisite to the program's response to chemical or biological attack. Because public health and law enforcement have overlapping approaches and goals to their investigations, it's important that public health workers such as epidemiologists and law enforcement officials collaborate to both enhance and protect the integrity of their investigations. LRN reference laboratories test hundreds of white powder letters for bio-threat agents every year. They have chain of custody procedures, and again, collaboration with local and federal law enforcement is really important for evidence preservation that can lead into a trial. Next slide, please. So, after the September 11 attacks on the World Trade Center, Pentagon, there were letters filled with white powder containing anthrax spores that were mailed to two senators' offices and news media agencies along the East Coast. And authorities recovered four of those letters. The powder from those letters contaminated the postal facilities that they were processed through as well as the buildings in which they were opened. And the first case of inhalation of anthrax was diagnosed on October 4 of 2001. During October and November of 2001, there were a total of 11 confirmed cases of inhalation of anthrax and 11 confirmed cases of cutaneous anthrax. And of the 22 people that were sick, five of them died. All of the people who died had inhalation anthrax, which is the most serious form of the disease. But the LRN was poised and ready at this time to respond to biological attacks, and they played an incredibly important role in the detection of anthrax during this time. LRN reference laboratories ran more than a million tests on approximately 125,000 samples in this time period. Next slide, please. I want to talk a little bit about tularemia, which is a disease that can infect animals as well as people. Animals such as rabbits, hares, and rodents are especially susceptible, and they often die in large numbers during outbreaks. And people can be infected in several ways, including tick and deer fly bites, skin contact with infected animals, drinking contaminated water, inhaling contaminated aerosols for agricultural landscaping dust, or laboratory exposure, which is more rare. Francisella tularensis is the causative agent of tularemia and can also be used as a bioweapon. And so LRNB laboratories are poised to detect this endemic disease. Tularemia has been reported from all states except Hawaii, and the LRN reference laboratories have the tools and training required to be able to detect tularemia. Next slide. This is another example of an endemic disease that the LRNB reference laboratories can detect, and its plague, which is a disease that affects humans and other mammals. It's caused by the bacterium Yersinia pestis. Humans usually get plague after being bitten by a rodent flea that's carrying the plague bacterium or by handling an animal that's been infected with plague. We still have cases of plague, as the map shows, in the United States. And without prompt treatment, the disease can cause serious illness or death. Presently, human plague infections continue to occur in rural areas in western United States. Significantly more cases occur in parts of Africa and Asia. But as with tularemia, the LRN reference laboratories detect several US cases of plague every year. Next slide, please. This slide describes the case of a man who traveled through several states over a three-week time period where animal anthrax had been detected in the past. So, this man developed symptoms, went to a hospital where an excellent medical team recognized the signs and symptoms and understood the associated travel history. They reached out to the Minnesota Public Health Department and quickly sent specimens to the LRN reference laboratory for testing. And this is

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just another example of the collaboration within the network to be able to expedite testing and subsequent proper medical treatment. And fortunately, this man survived his infection. Next slide, please. OK, now we'll move on to detecting emerging infectious diseases, which is-- in the years since its creation, the original focus was really on bio-terrorism threats, but since the LRN has been created, it's played an instrumental role in improving domestic public health infrastructure by helping to boost state, local, and federal laboratory capability. And this infrastructure has been incredibly important in responding to emerging infectious diseases, such as the first SARS coronavirus, MERS coronavirus, and Zika virus. And this is where our collaborations with FDA and CMS are just critical to be able to help deploy diagnostics to these LRN reference laboratories during a public health emergency, so we're grateful for their collaboration. In 2014 LRN reference laboratories were prepared to detect imported cases of Ebola, first using a test developed by the Department of Defense. Next slide, please. Currently, the LRN uses two real time RT-PCR assays for the detection of Ebola virus RNA in patient specimens. And there are 53 reference laboratories that have this testing capability, and these laboratories have tested approximately 180 patients’ samples-- specimens since 2014. And as you're all aware, there's been two recent Ebola outbreaks in 2021, one in Guinea, and the other in the DRC. And although the risk of travel-associated Ebola cases in the United States is very low, the LRN remains poised to respond. And we have, in the past several weeks, had several consultations with certain states with returning travelers. And in fact, an LRN laboratory received a suspect Ebola specimen just on Monday from a returning traveler from Guinea for testing. Fortunately, that patient was negative. Next slide. With CDC support and expertise, our LRN laboratories are more prepared than ever to quickly identify threats. Labs are better equipped, so they use more advanced technologies. We have veterinary, agriculture, military, food, and water testing laboratories that are also part of the LRN system, which is really important to test emerging infectious diseases and other agents, and other types of specimens besides patient clinical specimens. And state and local authorities have trusted data to make sound decisions in an emergency. And the infrastructure of the LRN really has provided many resources for emergency response, as shown on this slide, including standardized readiness of procedures, equipment, training, testing exercises, to be sure the laboratory staff can be able to complete the test and report that test appropriately. And these resources have been leveraged by LRN laboratories for all public health emergencies if needed, which occurred during influenza H1N1 in 2009, and of course, more recently, for 2019. So that infrastructure is really important to be able to respond to emergencies. Next slide, please. And as you're aware, there's lots of CDC resources that are available and that are utilized for laboratory response activities. When it comes to making time sensitive decisions about public health emergencies, having that accurate and reliable data is critical. Decision makers use these trusted results from LRN laboratories to help guide public health decisions such as deployment of pharmaceuticals, the implementation of community protection measures, and to treat and respond to emerging and evolving public health threats. Next slide, please. So now I want to talk about our current capabilities and some of the challenges and some of our future work just briefly. Next slide, please. So LRN reference laboratories utilize many types of tests for detection of bio-threat agents. Some examples include traditional microbiology techniques, such as growth on selective and non-selective media, bacteria, virus lysis, or biochemical tests, microscopic detection of bacteria using fluorescent probes, allele antibodies. They use serology tests to determine if a patient had a previous exposure to a pathogen. They use real time PCR techniques for biological threats and emerging infectious diseases. We also have multi-agent environmental screening tests as well. Next slide, please. Of course, there are lots of challenges to detect biological threats, and these are just a few examples of those. And I think many have been highlighted during the COVID-19 pandemic. I think the pandemic has really emphasized the importance of facilitating communication of laboratory testing results. And I think the good news here is that there's a lot of investment by CDC and other agencies really so we can improve this area. I think it's really important. A lack of clinical suspicion or a lack of information, such as if a patient can't provide travel history, that could possibly delay ordering the right diagnostic tests. And of course, it's always challenging when a new disease emerges, and diagnostic tests don't exist. As we all experienced this past year, that becomes a critical issue. And again, that's where our collaboration with FDA and CMS and all of our LRN partners really help in this area. We're also concerned with antimicrobial resistance, as we all are, and making correct decisions on treatment in those cases. In the area of some of the bio-- traditional bio-terrorism agents, there's not a lot of data around antimicrobial resistance. And so, we're working with Asper and other partners to look into this area. And I think also, another challenge is the emergence of any engineered organisms. So being able to detect something that's been genetically altered purposefully is also a challenge that we're certainly looking into. And of course, as always, biosafety and biosecurity are always incredibly important to consider when handling any biological agent. I think the challenge definitely comes in when we have a new emerging infectious disease. Next slide, please.

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I wanted to end by talking about some of the future work that's ongoing in the LRN. It's certainly been very challenging and difficult over the last year, but we do have several projects, as I mentioned, investigating antimicrobial resistance mechanisms and the new associated genotypic changes in bacterial bio-threat agents. We also have projects utilizing mass spectrometry to detect the activity of toxins as well as our structure. And something else that we did in December was put out a broad agency announcement for competitive selection of research proposals. And we have received several proposals for development, validation, and deployment of existing innovative technologies to detect and characterize existing and novel pathogens associated with a bio-threat event or something that could cause a novel emerging infectious disease outbreak or a public health emergency. And I wanted to mention that we require that these solutions include a framework for data reporting and analytics that are necessary for determination of public health action. And we're currently reviewing those proposals right now, and we look forward to new collaborations with new partners. Next slide. So, this is just a brief summary. I hope that you have a better understanding of the LRN and what it is we do today and what we look to do in the future. We'll continue to experience new and emerging infectious diseases due to many factors, as I've listed on the slide. And I think we all agree that we need to continue to invest in preparedness activities for all of our laboratories. There are a lot of challenges that exist, but we're fortunate to have so many wonderful collaborators and partners. And just want to thank you again for all of your attention this afternoon. CLIAC CHAIR: Thank you, Dr. Villanueva. God, it is amazing, the broad diversity of what is available to us through the LRN, and we thank you for that. This ends our updates from our partner agencies. We are going to go into a one-hour break. CLIAC members, please ensure you are on mute, and turn off your video, and come back at 3 o'clock Eastern Time. California, that's at noon, and you guys in the middle states, you figure it out. And for the public, a reminder. Public comment is available. It is limited to the topics on the agenda. If you've not already signed up, please email CLIAC@CDC.gov to get on the agenda. [CLIAC DFO] you popped up briefly. Did you want to make a comment? CLIAC DFO: No, sorry, [CLIAC CHAIR], I was just wondering, since we have 10 minutes on our schedule, whether or not there were any urgent questions from members of any of the presentations. OK. [LAUGHS] CLIAC CHAIR: Yeah, I see now hands up, so we're— CLIAC MEMBER: Thank you for the comments. They were excellent. CLIAC MEMBER: Thank you. I was going to take advantage of the few minutes. It's not an urgent question. They were excellent presentations. And I did have a couple questions. And one of the ones I wanted to ask was, [CDC EX OFFICIO], when you were talking about one lab, have you reached out to the veterinary diagnostic labs? You mentioned Caleca labs, and maybe you were including them in that group. But the recent experiences that we've had, I think really point to the importance of connecting with our veterinary diagnostic lab colleagues as well. CDC EX OFFICIO: Thanks. Thanks, [CLIAC MEMBER], for that feedback. I'll have to check in with the training workforce and development branch to know if the current partners including veterinary partners. But we will-- I'll get you that feedback. CLIAC MEMBER: Thank you. CLIAC CHAIR: I know [CLIAC MEMBER] has put in the chat, he is wondering if there's contact information available for the speakers. I know there's some on their title slides. I don't know if you need more than that. CLIAC MEMBER: Hey, [CLIAC CHAIR], could I just check? We will be able to ask questions after the break, or this is the only time we can ask questions? CLIAC CHAIR: This is the best time to ask questions of what we just heard. The public comments-- the discussions afterwards will relate to those sessions. CLIAC MEMBER: Well, then I'd like to just make a comment to [CMS EX OFFICIO]. And I think it's a very great progress that the CMS has made in terms of communication. And this is more of an issue of the modernization of government. Because I spent a lot of time answering questions about the form 116. And it made me ask the question for the future. Do we really even need to replicate paper forms on website systems? Meaning, could we not eliminate paper forms or the way they are laid out in the future and only keep the questions in a web format, where it's much easier to provide the guidance that you've already helped try to provide, but we don't have that complication of this box versus that box on one thing? And of course, I realize that maybe in the future, should we have a catastrophe and we don't have the internet, that

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may be a time to bring forms back. But let's hope that isn't the case, and let's try to move away from forms that we convert into website capability. Comment? CMS EX OFFICIO: I think that's a great question you're bringing forward. We have internal talks right now to actually have our entire process be electronic, and we are updating our data systems. And so, with this update, we'd actually be able to have a web interface form and then have that information be collected into a database. And then another thing that you're bringing up, for the reference laboratory material, they'll be actually able to interact and find out when their CLIA certificate is also entered into our system. And so that interaction of having a form and having an online payment and having one seamless system is something that we are taking on. And yes, that is a challenge, but we're going to take on that challenge and be successful with doing so. So, your comment is right on point, and we thank you for it. CLIAC MEMBER: Yeah. Thanks for your response. CLIAC MEMBER: Yes. So, my question would be to [CMS EX OFFICIO] and also to [FDA EX OFFICIO]. My question is, today, with all the challenges that have been happening in assisted living facilities regarding COVID, many people are moving to change their decisions to-- instead of nursing homes, to be at home in their last days, like for hospice and for critical care they used to get in a nursing facility. And what this has done is it's really raised the urgency of rapid diagnostic testing for those caregivers who come and see patients at home and those people that are now living at home, either if they need assisted living or if they're just now, instead of in nursing homes, they're at home. What is being done to escalate the capabilities of these rapid diagnostic tests for distribution to home care? Because the at-home tests, the over the counter tests, they're not really easy to find. You can't get them. But I know with CMS, this is major, because I know there's many people that I know that were going to go into nursing homes. Now their family is caring for them at home. And the urgency to be able to test caregivers as they come into the home, to make sure that they are free from spreading COVID, even with the vaccines, since we know the vaccines can't prevent you from getting COVID, what are we doing to increase the urgency of getting tools for those people now seeking to live at home in their last years? CMS EX OFFICIO: I'm going to let [FDA EX OFFICIO] respond first. FDA EX OFFICIO: Yeah, I'll respond first. So obviously, we've been authorizing a lot of tests and a lot of different formats of those tests, including home collection and rapid tests that can be performed in a matter of minutes, and open up the recent new pathway to serial test and allow those tests to have the claim. But we've also said that any test that's been authorized and isn't limited in any way to only symptomatic people, that they can be used in screening. So those health care entities-- it's a very important topic. Our seniors are very important, and making sure they're safe in the home, as well as in congregate settings, is important. And it's why we worked so hard to authorize tools to be used in that setting and to be used by employers, say, of home health care workers to serially test their workers. And our current thoughts from the FDA is those workers should probably be tested at least once a week if it's by a molecular test and twice a week if it's by an antigen test. I'll let others, and perhaps some from the CDC, weigh in as well. CLIAC MEMBER: Monique, is this coming up with you at all at CMS? Is anybody trying to address this problem? CMS EX OFFICIO: Yes, we just had this topic today for the use of over the counter tests and in various settings, and we're having conversations-- this is within another division-- within our quality, safety, and oversight group. And we are having conversations with them, and we will move forward and actually take your comment back to our other division. CLIAC MEMBER: What is that division? CMS EX OFFICIO: It's the Department of Nursing Homes, but I'll actually— CLIAC MEMBER: Oh, OK. CMS EX OFFICIO: --provide it with-- I'll provide it today, the name and the contact information. But we do actually have another division where they actually have oversight over our nursing homes. CLIAC MEMBER: OK. And the last thing I'll add is, there are now at least four countries that are using rapid diagnostic tests and giving them to the public as a public health emergency issue release, these other countries, Greece, Austria, the UK. What is our government doing now to start to provide these, just like they're doing in other countries? And many of them are providing them for free, because the urgency is to keep people being safe, and you need to be able to be proactive to make sure that those people without symptoms are not spreading this. So, is there anything going on within our government today that is related to what other countries are doing for their people?

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FDA EX OFFICIO: So, there's a number of efforts along those lines. One is NIH just started a home testing study in North Carolina and Tennessee to prove that this kind of use by citizens on a regular basis is effective. And the department and administration, both current and prior, made purchases of a number of these tests and made them available, first to nursing homes. And I believe efforts are being made along those lines as well now that more tests are available. CLIAC MEMBER: OK, thank you. Thanks so much. CLIAC MEMBER: And [CLIAC CHAIR], hey, maybe you didn't want to drag this out any longer, but I just wanted to get back to Collette's presentation as well and endorse the work of DLS, which I think our committee has heard in the past. And it's making great progress. But I encountered a very surprising situation with our work overseas when I was informed that the European Union, particularly Germany and then Africa, would not accept our encoding, LOINC encoding of COVID-related tests and that they are requiring those to be converted into SNOMED. And I just thought that'd be an important issue for us to be aware of, that, for international purposes, LOINC will not be acceptable. CLIAC MEMBER: Here, I'll be brief. Thanks, [CLIAC CHAIR]. And thank you for all the presenters. It was great. All right. This is maybe a question or something that we might want to look at collectively now. And I think this will be input to the CLIAC regulations assessment work group. But we've just gone through with what you-- what I would call a natural experiment in terms of easing some regulations and pathologists working at home, and so on and so forth. And that came up in our personnel work group as well. And so one of the questions I have is whether, in fact, any of our federal partners have been collecting outcomes data that might be informative as we look at those regulations to inform the quality decisions that have been made by virtue of the pandemic, that maybe we would have taken a little bit longer to study, and if we can use those natural experiment data to inform the work group discussion. Thanks. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I've seen a number of letters submitted for public comment that address this issue. I did not see outcome measures noted in that, but we will be talking about that subject later. And, [CLIAC MEMBER], you just triggered a reaction, as I was given 18,700-- I'm sorry-- 1,877 tests for which I have to assign both the SNOMED and the LOINC code to do population reporting, and I don't know where to find the time for that. CLIAC MEMBER: [LAUGHS] Good luck. Now you prompted me again, and sorry for that. But could I ask Tim then one more question? And it relates to what [CLIAC MEMBER] getting at. So, of all the assays that were submitted to the FDA for review, in the end, were all of them approved? 20%? 4%? Or are people making tests out of matchboxes in their garage and sending those in for e-way approval, or are the vast majority of them high quality tests which eventually lead to FDA approval? FDA EX OFFICIO: Unfortunately, not all of them are high quality. And since we don't make negative decisions public, this panel and others are not aware of all the things we do to protect the public. I think some of our federal partners know about those. When we-- by and large, those we authorized, when we've had an issue, we've made a very public statement about it. And those are fortunately very far and few of all the hundreds of authorizations we made. And we do obviously see a lot of data pre-market and post-market and among the complaint handling system, including MDR reporting, and even through our email box. So, we carefully monitor as best as we can with the current system the safety and effectiveness of the tests that we've authorized. But we have denied on data grounds hundreds of tests. CLIAC MEMBER: Thank you. CLIAC CHAIR: [CLIAC MEMBER], the final session of this meeting will be addressing point of care testing, self-collection, and self-testing, and that might be an opportune time to dive deeper into mass distribution of test materials to non-traditional sites. I'm thinking of the way the mass vaccination sites came up overnight at no charge. Is there an analogy for laboratory testing? CLIAC MEMBER: Great. Thanks so much. CLIAC CHAIR: Are there any other comments? I'm sorry. FDA EX OFFICIO: I wanted to follow up on one other comment about what we're seeing in tests. I'll just be frank, as I am normally transparent. People know that. We've seen a growing number of data integrity issues among test submitters. This basically means they did something with the data, manipulated the data, perhaps made up the data, or perhaps took the data from another developer. And who knows where that came from. This is an increasing problem at the FDA, and it is always a challenge to try to identify data integrity issues and solutions. I think, as we can make some of these events’ public, we may do that. But I think it's an important consideration when discussing what the FDA does and how they do it. CLIAC CHAIR: Well, that was a rather chilling statement. Thank you.

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FDA EX OFFICIO: [LAUGHS] We have an important job, and we work very hard at it. And it's a very challenging job sometimes. CLIAC DFO: Thanks, [CLIAC CHAIR]. I just wanted to try to begin responding to [CLIAC MEMBER] observation and question around the natural experiment of COVID-19 from the point of view of clinical laboratory regulation oversight and practice. And I do agree. I think we collectively are acquiring a tremendous amount of outcome data that can be used for us to critically evaluate our systems. I'm not individually confident that we have organized all of that outcome data in a way that we can use it clearly to make decisions right now. But I think we need help from the community to understand that outcome data and connect it to the regulatory systems. And then I will say that tomorrow we are having a session, and I was just trying to page through the agenda, which is specifically designed to look at the changes in the regulatory system that have been made during COVID to try to begin that conversation. So I think we'll be able to talk a little bit more about this tomorrow, but I think we still, as a community, have more work to do from the perspectives of deciphering very specific outcome data and linking that directly to specific regulatory changes. So, we look forward to your assistance in that regard. CLIAC CHAIR: I see no hands up. I see nothing in the chat. I'm going to count to three. One, two, three, go for break. Turn off your video. See you at 3:00.

❖ Presentations and Committee Discussion CLINICAL LABORATORY MEDICINE IN THE AGE OF COVID-19 Clinical Laboratory Perspectives on Laboratory Developed Tests

Introduction to Topic Valerie Ng, MD, PhD, CLIAC CHAIR CLIAC CHAIR: Thank you for being on time. For those of you who are here but your video is turned off, would you please turn it back on? Thank you. It is 12:01. I will give some housekeeping announcements. And I'm hoping Jordan and Carol will join in the meanwhile. I'm delighted to announce the first topic of this CLIAC meeting. It is the clinical laboratory perspectives on laboratory developed tests-- or LDTs, as we know and love that term. I will provide an introduction. It will be followed by 2 presentations by doctors Matthew Binnicker and Dara Aisner. These are presentations 8, 9, and 10 in the agenda. Afterwards, we will have public comments. We have received four so far. One from the Association of Public Health Laboratories. It is a written comment that is available online only. So, It's there for your review. One from Dr. Eric Konnick from the Association for Molecular Pathology, one from Dr. Medhat Askar from the American Society for Histocompatibility and Immunogenetics-- or ASHI. And one from Dr. Joseph Saad from the College of American Pathologists-- or CAP. A reminder for the public members. If you would like to speak on this topic and you've not yet submitted one, please contact and email cliac@cdc.gov as soon as possible. So, I would like to move into this afternoon session. Thank you all for attending. The focus of this meeting is a continuation of the fall 2020 theme, which was clinical laboratory medicine in the age of COVID-19. Through this series of presentations and committee discussion, I'm hopeful the collective wisdom of this expert group will have ideas as to how we manage the next wave of this pandemic or the next pandemic. Next slide, please. The first session is titled clinical lab perspectives on lab developed tests. While the focus of the presentations will include COVID-19, LDT specifics, the presentation will also focus on the clinical laboratory perspectives of the LDTs. The two presenters have been mentioned, but I'd like to give you a little bit more detail. Dr. Matthew Binnicker is a professor of laboratory medicine and pathology, the vise chair of practice in the Department of Laboratory Medicine and Pathology, and the medical director of the Clinical Virology Laboratory in the Division of Clinical Microbiology at the Mayo Clinic in Rochester, Minnesota. Dr. Dara Aisner is an anatomic and molecular genetic pathologist and associate professor of pathology at the University of Colorado School of Medicine in Denver, Colorado. Next slide, please. As you listen to these presentations and reflect on your experience with LDTs, the questions for your consideration are listed on the slide. During these committee discussions, please focus on the concerns of the laboratory community and the confusion in the laboratory community on the LDT issue, including when an emergency use reauthorization-- or EUA tests becomes an LDT. And which LDTs require formal FDA review. With that in mind, I would like to move to our first presenter, Dr. Matthew Binnicker. The floor yours, Dr. Binnicker.

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Challenges and Opportunities Surrounding Laboratory Developed Tests as an Essential Component of the Pandemic Response Matthew J. Binnicker, PhD, D(ABMM) DR. MATTHEW BINNICKER: Great. Thank you, Dr. Ng. And Heather for inviting me to present. I'm honored and privileged to have a chance to share our experience at Mayo Clinic and bringing up a laboratory developed test for SARS-CoV-2. And also, to be part of this really important discussion. So, before I dive in, I just wanted to provide a high-level summary of our Mayo Clinic laboratory practice. We provide laboratory testing for our patients in southeastern Minnesota, for our Minnesota campus. But we also have the Mayo Clinic sites in Arizona and Florida that also have local practices that care for patients. In addition to our academic community-based practice, we also are a reference laboratory that receive samples from all over the United States and countries throughout the world as well. And have supported not only domestic but international testing for COVID-19. I first wanted to provide just a little bit of background on how our thoughts evolved with relation to testing for COVID-19. As everyone on this call knows very well, the first case in the US was identified in late January. But by mid-February, we were starting to see increased number of cases in the US. And we had a call of our department leadership at Mayo Clinic on February 17th. And at that point, there were now increasing number of cases, and our attitude changed at that point from wait and see to we need to be prepared. We were competent at that point that at some time, whether it be days or weeks down the road, that we would have patients who would be seen at one of our Mayo Clinic sites who would need to be tested for COVID-19. And we knew that rapid answers for our physicians would be important so that they could manage those patients, so that we could isolate those patients and prevent transmission. And so, we made the decision on February 17th of last year to forge ahead with developing our own molecular tests for SARS-CoV-2. And we also made the commitment on that day that if we were going to move forward, we needed to have a test up and running within four weeks, which is a huge accomplishment for a clinical laboratory. Usually, a clinical lab will take six to nine months at a minimum to bring up a new molecular diagnostic test. Sometimes it might take longer than that. We've had tests that we've worked on for one to two years prior to implementing. So, to say we wanted to bring up a test in four weeks was a daunting task. The next day, we assembled a team of 15 people. And you can see the group that was assembled here. This group represented individuals with expertise in developing molecular diagnostic tests. It also included, though, members who had expertise in building the tests in our laboratory information system and electronic medical records so that we could be working on that process in parallel to the test development, so that reports could be issued to physicians and patients. This group also included those with expertise in automation and programming robotics, because we anticipated large volumes of testing. Although we had no idea what that large volume would turn out to be. But we also included members with expertise in lab regulations, and those who had interacted with our partners at the FDA because of the EUA process. And we wanted to have those experts involved from the very beginning to help walk us through that process and make sure that it was efficient as possible. This team worked, really, night and day over the course of the next three weeks to develop a test for SARS-CoV-2. On March 12th, we ran our first test for SARS-CoV-2, and we also communicated to the FDA that we would be submitting our information for emergency use authorization. I will say, at this point, that the flexibility of the FDA in allowing clinical laboratories to begin testing prior to actually receiving the EUA, allowed us to test thousands of individuals and identify cases earlier. So, I think that that was a very good step in this early pandemic process. Over the course of early April, we worked with the FDA and they were very responsive in answering our questions. And on April first we were able to formally receive emergency use authorization for our lab developed SARS-CoV-2 molecular test. Of course, we faced a lot of challenges along the way, as did all laboratories who were involved in COVID-19 testing. I won't spend too much time focusing on some of the points that I know were discussed at your last meeting in 2020 related to access to positive samples, and all the supply chain challenges that laboratories have faced over the last year. I would just emphasize and reiterate that those challenges were real and significant, and even continue today. With regards to validation material, I can remember being on the phone with colleagues in China and Singapore in early March, trying to get access to samples. And that is a real barrier to overcome for clinical laboratories in bringing up new diagnostic assays. Especially for those that are novel, and we don't have a readily accessible panels to test. I did mention that the FDA team were great partners to work with throughout our EUA submission process. But the complexities of the EUA process are a challenge for most clinical laboratories. It is a resource intense process. And I think this comes at a time during the early stages of a pandemic when labs are very, very busy with testing for other infectious diseases and trying to build plans for testing for a novel or emerging infectious disease. The EUA process also was somewhat fluid, and made it, at times, difficult to predict exactly what requirements may be present in the coming weeks or months. We are definitely of the opinion that high-quality labs will produce high quality

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tests and results. And I think one of the points of emphasis and discussion can center around how do we get as many high quality laboratories both within the public health, and the clinical laboratory sector involved in the testing effort as early as possible during a pandemic, during an outbreak of a novel infectious disease to, again, identify cases and curb transmission. Some additional challenges that we faced in the early days of the pandemic, and that continued for months after, I wanted to point out, related to the transportation issues. Surprisingly enough. As I mentioned, we're a reference laboratory that performs a laboratory developed tests, also commercial assays. And of course, we rely on specimens coming from all over the country to be able to test those. And we did encounter issues, where because of airline transportation being grounded and other delays with transportation, that specimens getting to us were delayed. That also impacted our ability to access critical supplies and equipment. I remember during our first week of testing, we were waiting on a second piece of extraction equipment that was coming in from Europe to increase our test capacity. And someone on the loading dock in Italy tested positive for COVID-19, which shut down their loading dock, and so our needed piece of extraction equipment sat there for several days. And that delayed. So again, a supply chain challenge is unforeseen challenges with transportation. Even when an instrument would break and we would need a service technician or someone to come in from a company to train us on a new piece of equipment, those individuals oftentimes were not able to travel as quickly as pre-pandemic. And that can slow down the laboratory response as well. One thing related to how laboratories use their tests and interpret those tests relates to guidelines and guidance documents. With molecular testing, early on we were struggling with if patients need to be retested prior to release from quarantine. We have ongoing questions about the use of cycle threshold values. With serology, the question has been when to use. With the antigen tests, it's should we use? And so I think an important consideration for us moving forward-- I know it's challenging during a pandemic of a novel infectious disease-- is for us to partner together and put together guidance documents for laboratories both public health and clinical labs on the use and interpretation of new tests. So why was a laboratory developed test such an essential and critical component to the Mayo Clinic response? I think, first and foremost, our lab developed test provided early access to testing for patients in our local communities. We were in close contact with our state health department colleagues, with the CDC. And for us to be able to perform that rapid testing for those in our clinical and our local communities, the lab developed test was needed and played that role. Our laboratory also served as a key component in our state testing response. Again, we were working closely with our state colleagues and building up our testing infrastructure. And our lab developed test, over the course of the last year, has performed in excess of 560,000 COVID-19 tests, and identified about 35,000 positive cases. So, the impact of that test was significant. I can't underscore, though, how a lab developed test also helped our large reference laboratory expand its testing capacity. Shortly after we brought up our lab developed test; the first commercial system gained emergency use reauthorization. And we were able to then use the positive samples that we were getting from our lab developed test to validate the commercial systems. And we've continued to do that over the course of the last months and year. We now have 14 different commercial COVID-19 tests being run across our Mayo Clinic sites. And both within our practices and our reference laboratory have performed in excess of 4 million tests. So, while the lab developed test was initially targeted at meeting the local community needs, offering that lab developed test really assisted us in bringing up high throughput, high capacity systems that have served patients all around the country as well. So, of course, there have been a number of opportunities that we've identified over the course of the last year, areas that we can improve upon and lessons learned. I think one thing that has stood out to me is that widespread testing and high-quality laboratories, both within public health and clinical laboratories, is needed during the early phases of an outbreak like COVID-19 to prevent broad community transmission. I think clinical labs are essential because they are near patients. A lot of our patients are collected in the same building that I'm sitting in now. So those samples can be transported rapidly to our lab. And we now have systems that can get those results out in less than an hour because of new advancements. And lab developed tests helped not only our response, but responses across the country to provide increased access to testing during those early days of the pandemic. Another thing that has become so evident to me is that the partnership between our public health infrastructure, our industry partners, professionals and clinical laboratories, and our government is also essential in not only responding and closing out the COVID-19 pandemic, but preparing for future pandemics as well. Some additional opportunities and lessons learned is that as I mentioned earlier, the process of developing and validating a lab developed test in a high-quality clinical laboratory is a significant process that requires a lot of resources and a significant amount of time. Layering on the emergency use reauthorization process adds additional time and resources and complexity that I think many clinical labs in the United States aren't prepared to navigate. Although we were able to pull together a team of 15 people who worked night and day over three weeks to meet that need, I was talking with colleagues around the country in clinical labs, and oftentimes that responsibility fell on one or two people. And I can't

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imagine having to go through the process of designing studies, analyzing data, and submitting all of the necessary EUA paperwork by myself. And I know colleagues who did that. That occurs at a period of time during a pandemic when time is of the essence, where we need all of our laboratory professionals focused on overseeing testing during the earliest days of a pandemic or outbreak of an emerging infectious disease. So as I've thought about this, and talked with many colleagues over the last year, one idea that we've discussed is whether we could rapidly stand up greater access to testing through forming a network of centers for excellence or a pandemic response network that would include our public health labs and clinical laboratories. And I think this would be an opportunity for us to get testing in the hands of those who are near patients, near those who are needing to be tested in a rapid fashion, and really scale up our testing capacity across the country. I think our public health infrastructure, the CDC and our state health labs are best positioned during the early days of a novel infectious disease to design a new test, to develop that and validate it. And I think that will continue to be the case moving forward. One thing that I thought about is we likely need to involve our industry partners at very early stages. So that they can be aware of how these assays are being designed. They can begin to think about how they might be adapted to their higher throughput platforms. So that might be one area for discussion. As I pointed out, I think the FDA review process with the EUA is needed and necessary for initial early tests, especially for the CDC assay. All high-quality labs want to perform high quality tests. I think that is that's a given Again, coming back to industry. They play a unique role in that their best positioned for mass production of reagents, and they are producing high throughput equipment that many of our clinical laboratories have throughout this country. And of course, our government officials, I think, are working on and have eyes set towards creating stockpiles of necessary supplies in the future that laboratories can have access to, and allowing us to collect samples and get samples to our laboratories in a timely fashion. So how could clinical laboratories play a more enhanced role in this process? One idea would be for clinical labs to apply to be certified testing sites during an emerging infectious disease. They might have to show that they have the required equipment on site. For example, the equipment that the CDC uses for testing of their initial EUA method. Clinical labs could go through a pre-inspection process and demonstrate the ability to follow a CDC protocol. They may even need to go through a recertification process. And ideally, those steps would take place outside of a pandemic, so that we're ready to respond if an emerging infectious disease occurs. And then prior to clinical testing, I think it would be really beneficial for us to think about not only having those clinical labs perform their own internal validation, but if the CDC and FDA could put together proficiency panels that could be sent out to clinical labs just to demonstrate that they do have their method up and running. And it's performing as expected. Similarly, to how the state labs performed proficiency or blinded panel testing before they started testing for COVID-19. So just to summarize a few key points here. I've come to appreciate the testing with rapid turnaround time is really critical to prevent widespread transmission of a novel infectious disease like SARS-CoV-2. And lab developed tests, including the one that we brought up at Mayo Clinic, played a key role in that early COVID-19 response. It provided us with early access to testing for patients in our communities. But development and validation of those lab develop tests, those require a lot of time and resources that not all clinical labs have at their disposal to bring that testing up. To get to broad testing, we need to have our public health, our reference labs, and also our small community laboratories involved. I think it's an all of the above approach. Everyone is needed to stem transmission during the earliest phases of a pandemic. And again, I just can't iterate enough how that partnership that I have seen over the last year between public health, clinical labs, industry, and the government has provided a lot of benefit. And I think we can build off of that in the future to prepare and to establish a network that will allow us to respond even better in the future. So, with that, I just want to finish up. These are a few references that I just wanted to call out. The first is from the CEO and the past president of the American Society for Microbiology. There was a New York Times piece that called for a new kind of National Guard, where basically we need to be thinking about our testing a response similar to how we would respond with the National Guard and having a group of laboratory technicians and health care staff that we can call on. Because the staffing issues related to testing have been significant for clinical labs. And then the second reference is a review article or an opinion piece that I wrote for Clinical Chemistry on this topic, really emphasizing the importance of partnership and proposing some future ideas for responding to the next pandemic. So, I'll wrap up there. Again, just so appreciate the opportunity to share our experience. And I'll look forward to the question period. I'll turn it back over to Dr. Ng. CLIAC CHAIR: Thank you, Dr. Binnicker. We have three minutes before Dr. Aisner scheduled slot. And members have already lined up. We'll start with [CLIAC MEMBER]. CLIAC MEMBER: Thanks so much for the presentation. There's no doubt that LDTs saved the day before the commercialize assays became available. And obviously, your organization was one of those. The challenge that we had is very similar to your own. Because we had, from the day the patients or the travelers on the Diamond Princess came here,

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we had additional material that we were providing to other institutions for validation. But one of the things we lacked was prepositioned MTAs. And our regulatory people were demanding that before we sent that material out. So, the idea you have of a consortium, where MTAs are already in place-- and who knows which lab in the future is going to get the first samples-- that would be a very good thing to do. And even if the LRM could provide samples outside the LRM, that would be another solution. But if they can't, then the commercial laboratories, the private laboratories, and academic laboratories have to create that network that you described. Thank you. CLIAC CHAIR: Thank you. CLIAC MEMBER: Thank you. Thank you for your excellent presentation. You made some really great comments. And things from a public health lab perspective are very much needed. And I wanted to point out that when you talk about LDTs from the public health lab perspective, to have an exemption for that development because we have to be the first. Our first case came to Iowa on our March 2nd, and add to that, it was a very steep climb, the number of tests have been performed before our other clinical labs in the state got up to speed with the tests and equipment that they could use. So, I definitely see that prepositioning for clinical labs to be a very important point. I'd like to take it one step further, though, and when I get back to Dr. Julie Villanueva’s presentation on what we had in the prior session. Because the Laboratory Response Network is a wonderful platform to develop that. And going beyond the state public health labs to add those clinical labs in a prepositioned readiness state for those who could take on that capacity would be a great next step to further develop that Laboratory Response Network. So, thank you very much. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. And one final comment from [FDA EX OFFICIO] to Dr. Binnicker. FDA EX OFFICIO: Yes. Thank you so much for that excellent presentation. And I just want to let you know that I'm going to take the presentations back to the FDA and tell the people within the government. And you have some really creative, good ideas there. Just wanted to thank you. CLIAC CHAIR: Thank you very much. Our next speaker is Dr. Dara Aisner. Dara, take it away.

Moving Mountains: (R)Evolution of LDT Regulation in the Face of COVID-19 Dara L. Aisner, MD, PhD

DR. DARA AISNER: You would think after a year of doing this, I'd know how to unmute readily and easily. Thank you very, very much for the opportunity to speak today. It's really an honor to be able to present some of our perspectives. I've put a little bit of a theme in here around this lovely view that you might get from parts of Denver that includes Mount Evans, and I'll come back to that in a little while. But in the meantime, here we go. If I can get technology to work. I just want to start by saying that the experience I'm discussing today is really an amalgam of multiple separate CLIA laboratories. We have a very diverse set of laboratories here on our campus. And as the pandemic unfolded, we really tried to find ways to operationally utilize all of the infrastructure at our disposal. So, this meant bringing together laboratory directors across a wide spectrum of typical disease testing areas to really focus on deploying rapid COVID testing stand up. So, we did come together to do that. And I am going to talk about some of our frustrations we experienced. But that said, we are very grateful to the CDC and the FDA for their leadership through the pandemic. I'm required to mention that the opinions on an express are mine, and I'm not representing my institution. And all of this was done under the really, really amazing leadership of Dr. Ed Ashford, who I believe knows a number of you, and who told me to say hi on his behalf for those of you who knows. Now, here's the timeline. Everybody has seen a version of the timeline. I'm going to draw your attention to that late February to early March period. And for us, what this was really about was a realization about supply chain. And we'd really been counting, as a system, on using what was anticipated to be a large number of EUA assays coming down the pike. And in its early phase of March, it became very apparent to us that all of our best laid plans were not going to come to fruition because we simply were not going to get allocation on the platforms that we had on hand ready to fire off at will. So, we formed some working groups to identify opportunities to use existing infrastructure. And based on this, identified four platforms that we could theoretically ramp up fairly quickly. And while three of these were in the standard clinical lab using platforms on hand, we did explicitly look into how to deploy testing in some of the ancillary labs. My lab, which is called CMOCO-- C-M-O-C-O. And a lab adjacent to mine, which is the Colorado Center for Personalized Medicine, both CAP/CLIA laboratories that have infrastructure, et cetera, to deploy clinical testing. Now, because of supply chain issues and discussion about what supply chains we might be able to assure, we decided to take a big bite and validate off the Thermo Fisher Platform. And we were pretty excited about this until we sort of looked in detail at the IFU and discovered that the real time PCR instrument that was mandated was not one we actually had. And we actually called on the inventory services of our entire University, including all of our campuses, including up in Boulder

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to see if anybody had one of these instruments we could port down. I was on the phone at 11 o'clock at night with ABI reps, talking about if we can get an instrument, can you IQ it, OQ it? And we had numerous other very similar instruments, but not exactly the same. And even though we knew that we could manage to mitigate whatever differences were there between the on-label instrument and what we had on hand, we also knew that doing that meant that we would be in the territory of being considered an LDT. So, with that as the background, we decided to go ahead and tackle an LDT validation based on the Thermo Fisher Platform. And as long as we were going to do it, we may as well take some changes on board that would help our workflow. So, the Colorado Center for Personalized Medicine Lab, under the direction of Dr. Kristy Crooks, completed a full validation of that Thermo test in eight days. I cannot even tell you how hard they worked. It was unbelievable. And they also took on writing an EUA application. Now, we're not a reference lab. We don't have a lot of experience in that realm. And this was really a learning curve for our professional practitioners from the start. We really didn't have a regulatory staff we could call on to help with that. Now, quite frustratingly, just as we were sending our EUA off to the FDA, an update by a few came out and said, oh, that thermal cycler you have on hand, you can use it. But by that time, we had already done all the work and the EUA was on its way on email. So, we decided to continue on with the changes we had made. Now, shortly thereafter, we did hear back from the FDA, and that was really nice. But I'm going to dissect this a little bit because it was a little bit challenging for us. As you'll see here, you'll see that the author of this email references the policy for diagnostic test for Coronavirus Disease 2019. And it indicates that we may use the test without a new or amended EUA, where we've done appropriate bridging studies. And to be honest, our first reaction to this was, what? Really? We can do that. And what I will say is that in teasing through that documentation, I can see very clearly that the FDA stance of you can launch your test while you're getting your EUA test is there. And I truly echo Dr. Binnicker's kudos, because I think this was an absolutely paramount change that was really a game changer. But I really was not able to infer that that document meant that we could do a bridging study and call it good. And I would argue that this is one of many pieces of evidence that, in reality, I think the FDA and laboratorians can sometimes speak different languages. And it can be hard to understand what the message the FDA is trying to tell us without the experience to know, well, these specific terms mean the specific things in FDA language. And how that impacts those of us who are really nuts and bolts with our heads in assays all day. Now, back to that FDA EUA email. We were told it did not appear that we needed an EUA, that our changes were not substantial enough. And we therefore withdrew our EUA application. I'll come back to that. So, in the meantime, while that was going on, we separately were bringing up a separate LDT for alternate specimens. Tracheal aspirates, VALs, et cetera. Unfortunately, the assigned EUA reviewer was unfamiliar with our instruments and reagents, and this led to some confusion. And we did have some slow responses from the reviewer. In the middle of all of this, we were asked to do completely new validation experiments because criteria had changed. And then, there were some additional communication delays. Really difficultly, we were asked to acquire new specimens as part of this validation, and then cross-reference those validation samples against a CDC assay that we didn't actually have up and running. So that was an additional challenge. After there was an announcement that LDT review was not required, the whole thing just sort of dropped. We did not hear from the FDA, and we did not further pursue it. But I think this brings a point to bear, which is that there is variability of review. And what a reviewer brings to the table in terms of their expertise and opinion is not going to be uniform, because guess what? We're people. And so, I think that this variability of review is a serious consideration to think about. And when you think about what is required to deal with a large volume of testing, you have to have a very large staff of reviewers to keep up with that. And by definition, that means that there will always be turnover, which will only further exacerbate that variability of review. Now. Moving on to our third EUA. We found that as our case volume was going up and up-- this is in October-- a familiar story to everyone. We needed higher throughput solutions. So, we extensively validated and adopted pooling, and we submitted an EUA based on that prior I'll remind you we withdrew that EUA. We got lots and lots of emails about how this wasn't a priority and that was OK. FDA was pretty darn busy, and we get that. And when we did hear back, what we were essentially told was, hey, guess what, that assay that you're basing this on, you made too many changes, so we can't really consider this. So fairly contradictory messages in the sense that on one hand, we were told you didn't make so many changes that you need an EUA, but we had a hard time negotiating what to think about this in the context of those two separate submissions. It didn't really matter in the end, because by the time we got the response, we were done with pooling. The positivity rate was too high to pool and we had just onboarded a new very high throughput platform, which I know got EUA approval, I think yesterday. That's the Thermo Fisher Amplitude Platform. OK, so I'd like to say, OK, well, these were our experiences. Frustrating, yes, but everyone's in it together. Let's think about, how do we take these and turn them into

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lessons that we can adapt to. So, the first-- and very much on the heels of what Dr. Binnicker said, testing performed at a local level with local expertise is just more nimble than a boxed-and-shipped kit. I can do a bridging study if there's a supply chain shortage and I need to replace the constituent. Importantly, we can adapt to changes in biology and science, and I'll show you an example of that in a moment. And in-depth knowledge of that assay inherently mitigates the risk, that I think is attendant, if it's a box-and-shipped kit where the end user does not have that level of familiarity with all of the moving parts. Now, in terms of changes in biology and science, I think something that is particularly germane today is the evolution of the B117 variant. And here, I've shown you a couple of screen grabs from our Thermo Fisher assay-- adapted assay, I should say. And on the top panel is a typical pattern that we might see for SARS-CoV-2 positivity, positive RT-PCR curves for all three of the viral targets. Here on the bottom, we've got one from just last week. This is what we're calling S drop. And this is indicative of probable B117. Now, this is fine, except that what it means is that over time, I think it's likely that the criteria that are applied in an FDA IFU manner may no longer apply as the virus evolves and mutates and the performance characteristics of the assay, as it relates to those variants, is no longer exactly on target. And this is just to show you that over the last couple of months, the rate of cases that have that S drop pattern is going up and up and up. And so I really think it's just a matter of time before we start seeing a lot of borderline cases with S drop in terms of viral load, where we're not meeting the criteria for having two viral targets positive, which is the criteria for calling it. Now, the next thing I would like to highlight, is that there are numerous facets of testing that are important and obviously safe and effective are very clearly priorities. But if the testing can't meet other clinical metrics, like turnaround time, analytic sensitivity, then it isn't functional. And the example I would like to provide for this comes back to that EUA number two we submitted, which is alternate specimens. So, a really good example here is trachea aspirants. Trachea aspirants are a really important specimen type for the critically ill, intubated patients for whom an NP swab is just not a good consideration. And in reality, I don't think this is a common enough specimen type that any company is going to make an effort to create an EUA for that specimen type specifically. So cross studies and bridging studies to bring on alternate specimen types is just really critically important and it's a really critical part of the process that LDTs can fill. The other thing that I would say here, is that the timelines to deploy assays are critical. And this is where I'm going to pivot a little bit, thinking away from the pandemic of this last year, year and a half and thinking more globally in terms of pre-market review of LDTs. The scope of that means that major delays would likely become a way of doing business. And as an example, I'll point out that the very first full, as in de novo, approval, for a SARS-CoV-2 assay came just a hair over a year after the pandemic was declared. And the reality is that's what it takes to do the review. And so, this isn't meant to be critical, except it's meant to be realistic. I'd like to draw a little analogy. This is where my picture of the mountains comes back into play. Here on the western side of Denver, with my arrow here, is Green Mountain. This is a really popular afternoon hike for people here in Denver, particularly now that the weather is warming up. And this is something you can pretty much do on a whim. I can wake up Saturday morning and go, OK, I think I better think of a nice fun thing to do today. I'll go hike up Green Mountain. I just realized my fly-in didn't work, but that's OK. So, if we imagine that 2020 and how we think about SARS-CoV-2 regulation is like an afternoon stroll up Green Mountain-- I don't actually know the numbers inside the FDA. And I see Dr. Stenzel here and he can comment-- I decided to take a really aggressive approach and just assume that if only a quarter of all applications were approved, then that means that we were somewhere in the ballpark of 1,000 submissions in the last year. But the estimates for the number of LDTs in the US ranged anywhere from 60 to 100 times that number, with 15 to 20 times that number falling under the moderate or high-risk classification per FDA. I would argue to you that that is not an afternoon stroll up Green Mountain, that is a well-planned excursion up Mount Evans, or probably even more accurately, a big flight, some serious preparation, and a big trek up Mount Denali. OK, now, I historically don't practice in the infectious disease space. I am a molecular pathologist and pulmonary pathologist focused on cancer molecular testing. And what I would argue to you, is that cancer is a pandemic. And if we look at the mortality data of SARS-CoV-2 compared to cancer; I'm going to say I think they're somewhat comparable. So, the per capita mortality for SARS-CoV-2 is 170 per 100,000, and that's been over the span of the last 16 months. The per capita mortality for cancer in the US is close to 160 and that's been for decades. I think we need to think about testing for cancer treatment with the same urgency we have applied to this pandemic of the last year. So how can we think about oncology testing and SARS-CoV-2 through the same lens? One is that they're really very similar. One is that flexibility is absolutely essential. This can relate to the specimen type; it can relate to adapting to new and clinical information. As somebody who practices a lot in the next generation sequencing space, I can tell you that adding targets is something that is going to become much more common over time. And it's complicated by ever-evolving therapeutic targets. Boxed-and-shipped kits are just different from an assay that's developed in-house. And I'm not saying that boxed-and-shipped kits aren't good, they're really good for lots of circumstances. They have a really important role to play, as has been evidenced by this last year. But an experienced professional can mitigate risk when they all of those elements of an assay. So, I'd like to pivot this to some possible considerations.

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One is to consider the standards. So, we've seen over the last year, a large number of assays get approval through the EUA process. And that EUA process is a lower bar than what is considered a traditional FDA review. But the question really is, is it sufficient? And could this be a new bar, as opposed to a level of evidence for a PMA or 510(K) that's required? Would you apply this to all assays? Would you apply it to only locally deployed assays? I'll thank Dr. Stenzel for his really lovely perspective in NAJM and point to some of the data he provided here. Where this is an alarming number. 82 tests out of 125 with design or validation problems. And so, this leads to some questions. How many of those were major issues? How often were the actual assay conditions or the performance characteristics changed as a result of that feedback? And were the standards to mitigate risk for boxed-and-shipped kits being applied to LDTs? Can the equivalent be achieved with teaching laboratorians what you would like to see? And although there were 82 identified with design or validation problems, it says several have been denied authorization. So that sounds like the eventual approval rate was really quite high. Does that suggest other perhaps less onerous solutions? And is there room for dialogue about the standards for LDTs being different from a boxed-and-shipped kit? The next possible solution I would like to posit is to consider the expertise. The academic laboratory community has a wealth of knowledge, and the question really is, is there a way to engage that wealth of knowledge in this desire to review testing? This is an idea that, I don't know if it's come up before, but when I think about functioning as a professional, a good analogy is that we put trust in practicing physicians to prescribe opioids through a DEA license. That is an amount of trust we place in professional practitioners. Is there an analogy for how we might think about laboratorians? And instead of attaching that recognition and responsibility to the laboratory, attach it to the CLIA license holder. Now, I hate to say it, but you have to also consider the motive. And I'm not suggesting that every lab with a fiscal motive is going to cut corners, but certainly that is one of the things that might prime somebody, a laboratory, to be a little bit less compliant with some of these standards. And then, lastly, to consider existing infrastructure. This includes CLIA modernization, which I think does acknowledge the value and risk mitigation of professional laboratory practice. I'm going to stop by just mentioning that we actually have a consortium much like what Dr. Binnicker alluded to would be valuable. This is a consortium that I am a co-founder of that is centered around NGS testing in oncology, but we're expanding scope. In other areas. We're a consortium of 28 academic laboratories we shared in a reagent purchase. And we're working towards shared bioinformatics and many, many more things. But what I really think from the perspective of this talk, is that I see this as an opportunity to understand and minimize sources of variability. And much as Dr. Binnicker talked about the idea of centers of excellence, I think this is a starting point to think about that. And one of our plans for this consortium is actually to have standing MTAs in place, ready to go. So, in response to some of the things that have come up. Lastly, it really took moving mountains, and I think this is true with every academic center we all have, loading dock stories for sure. And every single one of these teams I have listed here is between 5 and 20 people. So, we're talking about well over 100 people at our institution that had to come together to pull this off. So, with that, I'd like to thank you again very much for the opportunity to participate today. CLIAC CHAIR: Thank you very much, Dr. Aisner. FDA EX OFFICIO: l was asked to make a comment. I'm going to ask whether or not it is acceptable to wait until the committee discussion. CLIAC CHAIR: We have our three public commenters lined up. FDA EX OFFICIO: Yeah, yeah, no, that's fine.

Public Comments CLIAC CHAIR: OK, you'll be first. We do have three public comments. We will start with Dr. Eric Konnick from the Association of Molecular Pathology. Dr. Konnick? DR. ERIC KONNICK: Right. Can you hear me? OK. So, I'm Eric Konnick, I'm the co-chair of the Association for Molecular Pathology's Professional Relations Committee. So, as I think all of you are probably aware, AMP is an international medical professional association representing approximately 2,500 physicians, doctoral scientists, and medical technologists performing laboratory testing based on knowledge derived from molecular biology genetics and genomics. The vast majority of our members work in CLIA certified, CAP accredited clinical laboratories, and AMP members were and continue to be on the front lines of the clinical response to the COVID-19 pandemic. So, the large network of molecular diagnostic laboratories and academic in team settings is a rich resource, and there's that risk for being undervalued, as evidenced in this most recent public health emergency, underutilized as well. To better

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understand the contributions of these laboratories and their tests, and making a response to the pandemic, I'd like to share some results from two surveys conducted by AMP during 2020. So, laboratory developed testing procedures, or LDPs, were an essential part of the pandemic response efforts. By August 2020, over 1/3 of the laboratories in our survey required using in-house LDPs as either their primary way of testing or to augment their testing capabilities. So early in the pandemic, the declaration of the public health emergency actually prevented laboratories from implementing LDPs early, leaving the country without any diagnostic testing options that could be used to better inform clinical care, and stem the spread of SARS-CoV-2 for weeks. And that was especially huge in the state of Washington, University of Washington, where I practice. The requirement to seek EUA from the FDA for tests for SARS-CoV-2, including LDPs, prior to being for patient care, was a drastic, unnecessary addition to the regulatory requirements laboratories are already subject to under CLIA. So once the updated policy from the FDA allowed laboratories to implement LDPs concurrently while obtaining an EUA, we responded rapidly. So academic medical centers were able to develop, validate, and start using their own tests, on average, in less than a month from when the FDA's policies changed. On average, community and commercial reference laboratories launched their tests about two weeks after that. This is all based on our survey data. So however we're navigating the EUA process, many laboratories reported that the FDA set impossible to meet requirements, such as very early on requiring an evaluation of more positive samples than were confirmed cases in the United States, and testing of select agents that were unavailable outside of VSL core labs. In August, almost 1/3 of laboratories reported they experienced hurdles of this kind while seeking an EUA, indicating significant barriers to obtain an EUA remained, despite changes to regulatory policy. So, in April 2020, AMP required that many laboratories deployed multiple testing methodology, as we see today, as part of our efforts to provide uninterrupted access to SARS-CoV testing while encountering supply-chain shortages. As the pandemic continued, the number of laboratories, particularly academic medical center and community-based laboratories, using only one method declined by 18% from April to August in 2020. So, requiring an EUA for each of these testing methods further hamstrings laboratories' ability to nimbly adjust to accommodate a supply chain issue or to maintain their testing capacity and meet patient needs. So, the recommendations from AMP-- so first, we think that CLIA should ensure that regulatory requirements for clinical laboratories are not duplicative or burdensome, especially during a pandemic. Maintaining the CLIA program as the agency responsible for oversight of LPDs will ensure that the US can rapidly develop and deploy the testing needs during any future public health emergency. Further, it will ensure that we have the diversity of assays to use, using different reagents, disposables, and approaches to maintain the resiliency of laboratories when faced with supply and chain shortages. Second, CDC should better leverage the passing expertise housed within molecular laboratories across the country, including academic medical center and community-based laboratories. Third, communication and collaboration between molecular diagnostic laboratories focused on diagnosis and patient care, and public health laboratories focused on surveillance and epidemiology, are essential. Courting their different roles not only enhances their respective values but results in an-- should see in response to a pandemic that cannot be achieved otherwise. So, thank you for your opportunity to provide comments today, the surveys I mentioned are available on AMP's website. CLIAC CHAIR: Thank you very much, Dr. Konnick. Our next public comments from Dr. Medhat Askar from the American Society for Histocompatibility and Immunogenetics. Dr. Askar. You're on mute. You're on mute. DR. MEDHAT ASKAR: OK. Good afternoon Madam Chair, and members of the Advisory Committee on behalf of the American Society of Histocompatibility and Immogenetics, ASHI. I thank the committee for the opportunity to present the views of our disciplined practice with respect to LDT regulation. I'm Medhat Askar, a professor of pathology and lab medicine at Texas A&M College of Medicine, Director of Transplant Immunology at Baylor University Medical Center, and the, as of the beginning of the COVID pandemic, the director of COVID testing at our institution, which really afforded me firsthand the experience of interacting with the FDA in the context of LDT while applying for EUA for a test developed in our lab. I'm the Immediate Past President of ASHI, past president American College of Histocompatibility and Immunogenetics, past division head of the ASHI accreditation review board, and member of the executive committee of the national polls. Today, I present ASHI, which is the world's largest organization of professionals in clinical apparatus disciplines of histocompatibility, immunogenetics, and transplant immunology. ASHI serves patients, particularly transplant and cancer patients, and laboratory practitioners at all levels, and the public by promoting excellence in clinical laboratory testing in the United States and worldwide. Thorough comprehensive constellation of professional services, including developing laboratory practice standards, offering external proficiency testing program, and the laboratory accreditation program for high complexity laboratories under CLIA. ASHI establishes at the highest of standards for laboratory practices. This is evidenced by ASHI achieving deemed status with government agencies, such as CMS and accrediting bodies, such as Joint Commission and UNOS, FACT, and NMDP. It is noteworthy that the majority of our tests are LDT. I would like to acknowledge the heroic and

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tremendous amount of work accomplished by FDA authorizing COVID diagnostics, as presented earlier by Dr. Stenzel. Regarding the matter of regulating LDT, performance in high complex laboratory CLIA, accredited by ASHI, we maintain at ASHI that FDA authorization is neither warranted nor feasible. It is not warranted since these tests are performed and subject to applicable CLIA and the ASHI standards with very strict requirements for staff credentialing, continuing education, maintenance of competency, equipment, qualifications, preventive maintenance, reagent QC, testing facility standards, and mandatory succession persuasion external proficiency testing. As to feasibility, the experience with COVID diagnostics authorization of FDA, will relatively limit the scope and expedited process of EUA, approved prohibitively prolonged for tests submitted by individual laboratories. As Dr. Aisner just presented and highlighted the delays and the variability in the process of the conflict in communication, and possibly abbreviated process than what normally FDA will do, which echoes my personal experience applying to EUA for COVID LDT developed in our laboratory. And that continues until today, even with the significant increase in approval rate from 100 tests per month in April 2020 to over 300 tests per month in April 2021. Given the experience during the utmost urgency in facing global pandemic with emergency procedure authorization of LDT for a fairly limited scope of number, ASHI's concerned with the practicality of projected timeline to authorize over 100,000 tests, LDT, across all branches of laboratory medicine, and arguably of urgency less than facing a global pandemic. Furthermore, laboratories performing histocompatibility, if they were forced to pursue this without predictable timeline, that could compromise their ability to perform critical testing needed for safe performance for bone marrow transplantation, solid organ, lifesaving measures. In addition, the majority of our laboratories are small with limited number of staff and resources to pursue the FDA authorization. And this could potentially limit access to these lifesaving treatments and would disproportionately affect minorities and patients of lower socioeconomic status serviced by smaller labs with the least resources. And to bear in mind that these are the populations most disadvantaged in accessing these treatments to begin with. Therefore, ASHI urges CLIA to draw upon these experiences and consider recommending FDA to waived authorization of LDT performant in CLIA high complexity laboratories accredited by ASHI. And I'll stop here and welcome any questions. CLIAC CHAIR: Thank you very much, Dr. Askar. final public comment is from Dr. Joe Saad from the College of American pathology. Dr. Saad? DR. JOE SAAD: Thank you, good afternoon. My name is Joe Saad and I'm the chairman of pathology for the Methodist Health System in Dallas, Texas. I'm here to represent the College of American Pathologists and appreciate the opportunity to provide comments to CLIAC on the topic of prospect clinical laboratory perspectives on laboratory developed tests in the age of COVID-19. As we heard, LDTs are integrally involved in the direct mitigation of COVID-19 crisis that increased demands for testing for accurate and timely diagnosis of COVID-19 infection. Appropriate processes and infrastructure should be in place to ensure that patients have timely access to diagnostic testing, and laboratories have the resources to support and provide needed testing. Specifically, they should include quick deployment of the emergency use of laboratory developed tests. Timely, consistent communication from federal agencies is essential in order to maximize the ability of laboratories to provide essential testing during a pandemic. While the FDA and CMS have made recent improvements, initial delays and shortcomings have affected the prevalence of COVID-19 testing in the United States. As physicians providing services during this unprecedented public health emergency, we have seen firsthand the role of LDTs contributed to the management to help manage and address this crisis. As documented by the media, the initial delays in testing contribute to the spread of COVID-19, impacting our most vulnerable communities and frontline workers, and straining health care workers and resources. As such, we are in a unique position to provide our perspective on lessons learned. When LDTs became available for clinical use for diagnosing COVID-19 infection, the volume of LDT applications for EUA exceeded the FDA's capability to manage and review the influx. Standards are needed that allow for third parties to assume some of these oversight responsibilities when the capacity for timely FDA review is exceeded. Once the FDA granted emergency use authorizations for COVID-19 LDTs, academic medical centers and clinical laboratories were able to quickly offer testing to meet the clinical needs. During the initial stages of the pandemic, LDTs were only available to identify COVID-19 patients that required isolation and/or treatment. Over the past months, the FDA changed its policies to allow states to authorize LDTs to detect COVID-19 for use within their state, without an EUA from FDA. This move was needed because of the volume of LDTs being submitted to the FDA for EUA, created a significant backlog that prevented LDTs and commercial kits from being available. To assist these state programs and laboratories, the FDA focused its efforts on establishing a standard for analytical performance, since the clinical validity of COVID-19 testing was well established. Pathologists and clinical laboratories are still facing challenges throughout the testing process, and supply chain issues remain of high concern. Our research shows that 45% of laboratories testing for COVID-19 have difficulties obtaining the testing supplies. While this represents an improvement since last summer, shortages are still a substantial burden on laboratories performing COVID-19 testing.

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From our research, laboratory directors cite problems requiring necessary reagents, test kits, plastic pipette tips, swabs and transport media. LDTs have made it possible for clinical laboratories to minimize these disruptions by offering additional platforms for testing. From our most recent survey, we know laboratories have responded to the pandemic by deploying multiple different testing platforms in order to keep up with demand and ensure that testing is available. Laboratory directors indicated they may have multiple versions of high throughput and non-high throughput testing platforms. Most practices reported using more than one platform. In fact, over 80% of practices use two or more platforms, and about 1/2 of respondents reported using three or more platforms, in our instance, three, in Mayo Clinic's, 14 or 15. Finally, the pandemic focuses the need for consistent policy and regulatory guidance. In August 2020, the directives by HHS caused confusion and liability concerns, since clinical laboratories developed or modified tests because of various challenges, were longer afforded liability protections that were provided under an EUA. The COVID-19 pandemic highlighted the importance of diagnostic tests and how important they are to help track and trace the virus and identify individuals needing quarantine and treatment. It also supports the CAP belief that a regulatory approach for the oversight of LDTs should be more flexible and build on existing frameworks and institutional knowledge while limiting intrusions and compliance burdens on laboratories. Thank you for the opportunity to comment. And the CAP looks forward to working with CLIAC, federal officials, and the clinical laboratory community to develop solutions for COVID-19 and any future pandemics.

Committee Discussion CLIAC CHAIR: Thank you very much, Dr. Saad. Heather, if we could get up the questions for the panel discussion? Dr. Saad's statement concluded our public comments, and while the slide is being brought up, [FDA EX OFFICIO] you've been waiting to make some comments. So, go ahead. FDA EX OFFICIO: Thank you. Yeah, I'll just speak broadly, I think, to comment on the last four speakers. And first of all, thank you. We at the FDA really appreciate hearing from stakeholders and we listen carefully. And it's important that we do that and assess what we've done, and throughout the pandemic we've done that, and we've altered our guidance and recommendations to adjust to the timely needs. In one of those was for LDTs on February 29th, 2020 to allow LDTs to be launched after notification of the FDA and not to wait on EUA authorization. And that did spur a number of tests over the ensuing weeks to be launched. We did, unfortunately, deny some LDTs, and we don't make those numbers public for any category. I did want to talk about current legislation that's been drafted. And there is recurrent legislation, there are grandfather clauses to allow most of the LDTs on the market to not come in. And there's also a pre-certification process whereby given test developer and academic center reference labs can submit one application for pre-certification in the category and not have to submit until the next certification time period. And so many tests will not be reviewed by the FDA if that current draft of the legislation remains. And the FDA does support a legislative solution to LDTs, and we would refer everybody who's interested to talk to Congress specifically, and not to the FDA, as they are leading this effort. Also, during the pandemic, and even up until now, I'm personally not encouraging full authorization submissions. And I have made it clear on multiple occasions in public that we place a priority, currently, on authorizing EUA applications, and not full applications, as long as there's a public health need to authorize additional EUAs. And the reason for that is if we've already issued an EUA and there's no need during the pandemic, to have a full authorization. So, any time that de novo might have taken is impacted by those priorities. Also, I just want to make it clear that the center that I'm part of, the device center, does not review the vast majority of transplant related tests. That is reviewed by the Center for Biologics and they may appreciate any comments that you might send their way. And I do appreciate all the comments, we take them seriously and I have noted the major comments and we'll bring back those to the FDA. Thank you. CLIAC CHAIR: Thank you very much, [FDA EX OFFICIO]. So, the two questions for panel discussion are up on the screen, and it's open for whoever wants to talk. I would recommend you put your request in the chat box so we can keep some semblance of order. This is not a shy group so it's unusual for no one to be lined up. Does anyone want to comment about your understanding of current LDT requirements and oversight responsibilities? CLIAC MEMBER: Yeah, [CLIAC CHAIR], I just can't type as fast as I needed to here. Sorry, I'll just jump in then. So, I guess with Tim listening in, is it correct, then, that the President of the United States could waived the requirement for LDT review during an emergency situation? Or does the identification of it as an emergency situation force the FDA to follow the directives in regard to review of LDTs? FDA EX OFFICIO: I can respond if OK. CLIAC MEMBER: That was my intent. Thank you.

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FDA EX OFFICIO: OK. Yeah, so for the past six pandemics, we've followed the EUA provisions and reviewed LDTs and authorized many. In all the prior pandemics, there hasn't necessarily been any need for the number of tests at this time. And then the other thing to note, is that back in August of 2020, the HHS under the leadership Secretary Azar did put out a statement that said that the FDA review of LDTs would no longer be a requirement. So that's a statement that HHS made. I'm just reporting that, and that's very publicly known. And those are my comments, specifically, here. CLIAC MEMBER: Yeah, hi. I've been out of the private lab world for a few years doing stuff at the HHS. But I have a question as to what proportion of the laboratory testing capability in the country, in other words, perhaps what percentage of laboratories actually are doing, or can do, LDTs? In Nebraska, there's quite a bit of laboratory testing capacity that's sprinkled across the state and numerous labs, often quite small ones, who early on had no supplies, but could have supplemented testing. So, I'm just curious from the perspective of proportion of labs, how big the LDT issue actually is. Thanks. CLIAC CHAIR: And was that a question to all of us? CLIAC MEMBER: I thought maybe [FDA EX OFFICIO] might know, but anyone may wish to respond. That would be great. FDA EXOFFICIO: Yeah, I can give some thoughts. So when, I think maybe 40 years ago, when the FDA decided they weren't going to actively review then LDTs, locally developed tests, it was quite a bit different than we see today. Back then, it might be largely microscopic review of a wet prep or something of that order. Or something that was very small numbers and was not very complex. And it was done locally. So, it wasn't a sample sent from across the country, and there isn't a connection from the lab to the local clinicians that have requested the tests. But things have changed. Things are vastly different now. The major reference labs have lots of LDTs in their inventory. And the government spends on LDT tests has gone up drastically. And the complexity of the tests have greatly increased. When you think of NGS tests in the bioinformatics, that's required to interpret them, those are some of the most complex testing that we've ever had in clinical lab. And so, it's a vastly different situation. And currently there is a dichotomy between requirements in order to market a kit from the manufacturer, and what a lab is able to do. And the playing field between those two entities is no longer level. And there's lots of thought and comment on those. So by and large, and to sum up, there are a lot of LDTs now and a lot of volume throughout LDTs and a lot of public expenditures on LDTs and that's the current situation. CLIAC MEMBER: OK, thank you. I'd just also like to comment, I think the last presentations were really excellent. Thank you. CLIAC MEMBER; Yes, hi, can you hear me? Perfect. I just wanted to address some of the questions that we have in front of us right now. And I think the first question is a really good one. It's to what extent the laboratories understand the current LDT environment. I know a lot of professional societies in this space have been active in terms of laboratory developed test oversight. And in fact, three of the comments that we had just before was from CAP, AMP, and ASHI. And pairing that with the second question, going back to the speakers that we've have also had, sharing the regulatory environment throughout the pandemic, and what we can glean from this experience and, looking forward, if legislation were to come through, in terms of laboratory developed tests regulation-- I just want to call out that it seems like the impression was pretty uniform across the three public comments as well as the three presenters, that there are concerns about patient access to testing through a more FDA-centric model, concerns about agility and rapid and urgent cases where tests are needed rapidly. I mean, the pandemic obviously is the prototype here, but I think Dr. Aisner's comment about cancer as a pandemic, it also really holds true. And [FDA EX OFFICIO] comment about directing comments to Congress, obviously very appropriate. These things are being debated in Congress through legislation. I did just, also, want to call out that there is some counter-legislation as well really focusing on modernization of CLIA. I think these are definitely viable regulatory pathways, and just wanted to make sure that was out there as well. CLIAC CHAIR: Thank you. CLIAC MEMBER: I also wanted to comment on the questions at hand. I think that by nature of requiring board certification for molecular microbiology and molecular diagnostics, that is a guardrail that should be taken into consideration. I think anybody who has a board-certified person, such as I mentioned during the COVID pandemic, are capable of launching LDTs then under pressure and LDTs all the time. We don't have the same, perhaps, level of understanding of what non-medically board-certified people have in mind. And there were some examples of in the moment, pop up laboratories who made the news in different states where testing wasn't exactly up to what would be standard. So, I think what people have talked about before, people who do this understand it. People who don't do it may not understand it and may not know how to follow the CLIA regulations to do a laboratory developed process. So, I think we have things in place, we're just maybe not using them properly to mitigate the risk. Because while there were a lot of for-profit businesses popped up, and they actually had access to reagents that we in the hospitals did not, and many of them-- I mean, I personally consulted

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ICU docs, other health care people, and you look into these laboratories, they're PhD nutritionists. They never performed a medical laboratory test in their life. Or they're some other kind of person who doesn't have any clinical experience. So I think if there were a national registry, just like we have the LRN, and we register all of our laboratories to deploy these things rapidly, we could do the same thing with board registered people working through the organizations, and requiring, maybe, some kind of preregistration. Does your hospital have the capability to perform a laboratory developed test or not? And if you do, then go ahead and do it and file your paperwork, and eventually it will be reviewed. But I think there should be maybe some more oversight on people who have never ever done that in their life. And now they're starting a business to buy TaqPath reagents or other things. I've had molecular vendors come to me and say, we're really worried about some of the laboratories we're selling these reagents to because they don't know how to do it. And we're just hoping that doesn't blow back on our reagents. So, I think we have to be realistic, there are people who do understand them in advance and maybe some that don't. And that also really speaks to the experience of the past year. Where the ability to do it was overridden by the fact that you could not get reagents because the for-profit venture capital funded labs, and in many cases, these laboratories that popped up all over the country to make some money on the pandemic had supply chains to these maybe more nontraditional companies developing reagents and assays. And I think it all-- I mean, it's very complicated, and it all ties in. But I see something like a registry that would allow you to do what you know to do with suppliers who are used to dealing with the clinical community. And that infrastructure, that standard upon which we all comply, I think should go a long way. And then people in the FDA and other regulatory agencies could focus on the people who are doing this for the first time. Really, it's like Niagara Falls. And how do you sort that out? And how do you protect the public from people who you think it's easy to do and don't maybe have the full understanding of the requirements and oversight responsibility? So that's just my perspective. CLIAC CHAIR: Thank you. You bring back this CMS talk about the 275,000 certificate of waiver labs, 40,000 within the last year, versus the 16,000 accredited, or certificate of compliance labs. How do you extend that quality across the mean populace? CLIAC MEMBER: Thank you. I wanted to comment. I really support what [CLIAC MEMBER] has just said. I think we need to look at this as a different category of testing. When an emerging pathogen is facing us, we need to be prepared in a different way. And having a registry of individuals that where there's a director that is prepared to bring all the lab-developed tests and has demonstrated competency in this area, is a much safer way to go. As Donna mentioned, it protects the public from errors in testing, and most importantly, part of that competency would be to report to public health, because we have to remember that state public health agencies, CDC, they're all looking for this data to know what's happening with this emerging pathogen. So, if we had a way for both public health labs, clinical labs, and others involved, there would be a much better process. I, too, was contacted by well-meaning individuals who say, I have this PCR testing capacity I want to bring on these tests. But they have no idea what it takes from the collection of the sample to give it to their lab. And then after you get a result, how do you report it to the appropriate individuals? And it's a whole testing process that you have to be competent in, not just performing a PCR assay or another test. So, I support this, and I think maybe it goes to the idea, could CLIA have a recommendation on a different type of oversight, or regulatory regulation, LDPs? CLIAC CHAIR: Thank you. CLIAC MEMBER: Thank you. I have a comment about the question to the committee about, do laboratories understand the requirements and the oversight? And it seems to me that that's a very broad question. Do all laboratories understand the LDT requirements? And I think I'm singing to the same choir as the last two commenters, no. Do many laboratories understand those requirements? But I also would point to laboratory developed test requirements, but that's a very broad categorization as well. There is, as one of the speakers pointed to, a different type of sample type that is validated against a current test within that laboratory's portfolio, which might be a fairly simple validation, versus bringing a de novo test for an organism or cancer. And so, I think, in order to answer the question to the committee, we perhaps need to refine a little bit about, what are the categories of laboratories? And then also, what are the LDT requirements? Because LDT, actually, is a pretty broad basket of requirements. Thank you. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yeah, I think [CLIAC MEMBER] captured a little bit of my thunder, but my main point, clearly not all LDTs are created equally. And some are fairly simple and straightforward, some are more complex. And I think the other issue is the new requirements that, for the new laboratories, most of them are not high complexity labs. They shouldn't even be thinking about doing LDTs or what constitutes that. And so, I agree with-- I forget who said it, but really, we may

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need to sort of tease out LDTs of different levels. Because that one way you changed the specimen time, for example, is very different than developing a new assay for an emerging infectious disease. And so, I think that probably most people don't understand it. Most major high complexity labs, I think, probably do. Although not the entire spectrum. But I do think we need to talk about this a little bit in more detail, and probably come up with different levels for where, really, that expertise is needed, where others can be more safely. CLIAC CHAIR: So, I'm going to want to make some comments now that I think I'm allowed to speak. What do laboratories understand about current LDT requirements? Both [CLIAC MEMBERS] commented on, it's a giant spectrum. At one end, is the thing I always use as my example, it's that pleural fluid cholesterol level. Please don't have the FDA walk in to see how I validated the performance of that assay. I do it five times a year. But on the other hand, what we're talking about today, is what the surge, the pandemic surge, uncovered. When we need to rapidly develop an LDT that has to be expanded nationally, if not larger, and how can we do it too quickly? We've heard the terms nimble and agility from both doctors Binnicker and Aisner's talk. I was hearing considerations about the building blocks for the system of the future, to achieve that nimbleness and agility. How can we leverage our academic centers, our centers of excellence, with the brain trust? To be able to assist the FDA, delegate in whatever capacity, so look at what we are developing as LDTs and to help move that through more rapidly. How do we rely on personnel requirements and competencies, licensure, even in the face of workforce shortages? How do we look at test systems that are present within each laboratory? I could never be part of this network, because until two months ago, I had no PCR capability. Yet I am a high complexity lab. How do we tease that out? How do we maintain the database for what contingency, and who's going to maintain that? And finally, the reporting. Thank you. We need IS on both sides on the laboratory sending side and on the receiving side. We can send all the data we want, but if it can't be captured, where do we find the resources to help with that search? So, on my thoughts, on number two, would we consider, as [CLIAC MEMBER] has suggested, is this deep enough where we need a work group to delve into this? Or do we have some thoughts about, do we want to, as a group, consider some recommendations? And I would throw out, do we want to consider recommendations based on building blocks of quality? Now I shut you all into silence. CLIAC EXECUTIVE SECRETARY: [CLIAC MEMBER] saying she'd like to comment, and [CLIAC MEMBER] also. CLIAC CHAIR: Thank you, ma'am. CLIAC MEMBER: Thank you very much. I think we're all in agreement, based on the past comments, that laboratories need to be refined and oversight needs to be refined. And perhaps the way that we do that, is the second question, is recommendations for regulatory oversight. One thing that occurs to me, and I don't know exactly how it would fit within the CLIA infrastructure, is something that my previous employer, the Joint Commission, offers as part of their accreditation activities are certification products. And is there a certification piece that the accreditors could offer or CLIA offers or whomever would be the appropriate entity to offer? That would be a laboratory developed testing development certification, that if you have that certification, you get to collect $200 and pass go or something along those lines. And then if you don't have that certification-- so that might be one way of working it into a regulatory process, but I think one of the speakers also suggested that perhaps there's a unique accreditation designation that could be applied to the folks that have shown their ability to apply the critical thinking skills that would be required to bring up de novo LDT testing. And again, kind of designate what special categorization we're talking about here. Thank you. CLIAC MEMBER: Yeah, so I'll be brief. So, thank you, those presentations were outstanding. And I also know we're not talking about oncology, but the point was well taken. I was watching, we were all nodding our heads. There was so much good in those presentations because we recognized them from pre-COVID. What COVID did, of course, is like just throwing accelerant on a fire, right? All the issues we knew were there just exploded on everyone, correct? So that's what we saw. So, my question is, are those questions specific for LDT in general, or are we talking another emergency situation or another pandemic? So, my question is are we going to look at this from a broader point of view? I know our mandate today is COVID. I'm totally on top of that. But I would like to put that out in terms of structure of what we're actually going to be discussing. CLIAC CHAIR: I would just add, I would love to hear about LDTs as the entirety. CLIAC MEMBER: Yeah, I guess I would too. But I do think we have two different charges here. We have the emergency situation, which, I mean, LDTs have been discussed wide and far for many, many years. We're not going to be able to solve all of that in our committee today. But I do think that there are clear guardrails that we can put into-- I don't know that it's a regulatory thing, or if it's an LRN thing. It's part of that registration, that if a bioterrorism event or an emerging pathogen, now that they're dealing with emerging pathogens, they've already got registry. And then you tick off what the laboratory has. Do they have board certified people? Do they have other LDTs? Do they comply with the CLSI 12 quality

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essentials? Do they comply with CAP recommendations? Or whatever that this task force maybe comes up with. It has to be fast. And then maybe that becomes the umbrella, after which the other broader oncology could be discussed. Because I don't really think we have time to wait, because there are still very good laboratories being held up and there are laboratories that have no business doing testing, doing testing right now. And I feel like it's our responsibility to come up with some kind of a structure. And it won't be perfect, and we know it won't be perfect. But it is an iterative process that could be deployed. I mean, we all thought avian flu was the next pandemic, and then here comes COVID. Avian flu is still a threat. Other things are still a threat, there's about 50 different pathogens. So, like every lab in America had to qualify themselves as what level of laboratory response network are you. Are you going to be a level 4 lab? Are you going to be a confirmatory BSL-3 laboratory? I kind of feel like there's some kind of structure there we could learn from, and then tie that into some type of a regulatory process. But we don't have all of these clear regulations and certification and board requirements and all this stuff for nothing. Let's deploy it. Let's face it, the people who did bad tests were not, that I could tell, in my reading of the New York Times and the Florida Papers, they were not ABNMs, they were not board certified molecular pathologists, they were none of those people. I know there are bigger issues that maybe I'm not considering, and it doesn't stop any laboratory from hiring a board certified person and getting in that registry, but it may stop some people who have no business doing it. Or at very minimum, it sets a bar by which academic laboratories, research laboratories, people that don't normally do this, would know what they need to put together. Maybe they want to get their CAP inspection ahead of time or buy a CLSI document and get on board with some of these requirements. I mean, I think we could do something simple and then revise it and refine it as we go along, because it's still an emergency. That's just my two cents. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, I've been maybe getting a little confused about the discussion, but maybe it relates back to what the questions were. Because maybe we don't understand all the regulations. But I was fairly confident that CLIA qualified and CAP inspected laboratories knew fully well how to put together an EUA. And, if anything, I think we should file a certification process in order to develop an LDT internally. I think we should endorse that as a process. The big difference here is that we are under an emergency declaration. So that changes the game significantly. But there is a whole host of emerging disorders and infectious agents for which there is no emergency declaration. So, we are still authorized to go and develop LDTs under that scenario. So, I'm not seeing exactly yet how we are coming down on this point. That we are arguing that we need the whole LDT issue studied again, and that the current regulations are not significant, or sufficient? Or are we saying that because the EUA was declared, that's what caused the problem? I don't need an answer right now, I'm just sharing that. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yes. Hi, how are you? Again, I just wanted to reflect back to the group. Another thing I am hearing uniformly is something needs to change. I'm also hearing that we want to make sure that whatever the change is, is that it efficiently identifies high quality from low quality, right? Another way of saying it is like weeding out the bad apples. My question to the group is more procedural, but as an alternative to some of the direction that's going right now-- right, we know CLIA was last revised in 1988. That was 33 years ago, right? 33 years ago, I had to get off the couch to physically change the channel of my black and white television. That's a very long time ago. Rather than overlaying an additional regulatory environment, what would it take to modernize CLIA? What, procedurally? And include some of these elements that we're talking about. CLIAC CHAIR: So, there's a CLIA statute, and there are the CLIA amendments. And I will let one of our-- Nancy or Heather or Wren address why they changed this. Statute is an act of Congress, or law. The amendments, I believe it's rulemaking. Looking at [CLIAC EXECUTIVE SECRETARY], she's nodding her head, so. CLIAC EXECUTIVE SECRETARY: Yeah, if it's a change to the regulations, it takes going through the rule making process, which is developing a proposed rule, getting public comment, and developing a final rule. But all that depends on what the change is. Because if it's something that goes back to what's in the law, that forms the basis for what the regulations require. So, I guess it all depends on the level of change, but there are a number of things that could be done through the regulatory process. But again, bear in mind that even when that is undertaken relatively quickly from the regulatory perspective, it's not in a realistic perspective. It doesn't happen overnight. CLIAC MEMBER: Thank you, yeah, and I appreciate the time it would take and here, we're having a conversation about a sliver of laboratory medicine, of laboratory developed tests. But again, to the thought that it has been 33 years, and

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thinking about all the changes, I would suspect that there are many other areas of CLIA that would benefit from some modernization. CLIAC CHAIR: And I would just comment that in its inception, CLIA was intended to be very broad and very based on principles, not so much on technology. What we've seen in 30 years, tremendous changes in technology. But CLIA has been able to serve us well, even given that. I'd like to move on to [CLIAC MEMBER], and then [CLIAC MEMBER]. CLIAC MEMBER: So, like usual, [CLIAC MEMBER], I got my head going. So, I'm trying to think like this is not-- and, it was the comment that people have their boards in a lab, right? You can't just walk in and say, this is what I do. It's medical practice. So, I started thinking about two situations where this was dealt with in medicine in my personal life. One is that we have different levels of hospitals to take care of maternity patients. If you have a complex case, you actually have to get transferred. I have to be careful and say you have to, but you may want to escalate, and in fact, those are the guidelines. A complex, medical pregnant woman should not be taking care of in a lower level hospital. The other place to see it are the trauma units. And I thought of the trauma units because of the emergency, which labor and delivery can be as well. But trauma unit is actually, to me, an analogy of where, you want to call yourself a certain level of trauma unit, you must have these personnel. You actually have to have a certain number of personnel and they have to have certain training requirements. So again, that kind of helps with, this is all LDT or emergency. But certainly, if a lab, I consider is a practice of medicine. This has actually been done before. So, I'm just putting out their comment of a model that is very well recognized. And again, equipment falls into that as well. Like what equipment do you need on site. You have to have a certain number of ventilators if you're going to be an ICU high level. So, I just wanted to put that out there and thank [CLIAC MEMBER] like usual for her insight. CLIAC CHAIR: Thank you. CLIAC MEMBER: I agree with those comments, and I have a lot of sympathy with what [CLIAC MEMBER] was saying. I think we've seen some of the same things. As was said by 1% or I think quality labs produce quality results. And I know here, we've seen companies that have spun their own contracts with, for example, environmental testing labs and agricultural labs. And somehow these labs spool up PCR. So, they're regulated to do that, but they've not done any clinical testing. And I think you, as a lab professional, you just wonder-- you kind of know quality when you see it, and I wonder about these. So, I think that one of the issues that was mentioned by a previous presenter is doing a quality lab test. PCR is hard enough, but a quality laboratory test is, as you know, it's the front end and the back end. And I think companies that may be well intentioned just do not have that kind of experience to do a good quality management approach for pre-analytics and so on. One does worry. And so maybe, there are some tools, some of which [CLIAC MEMBER] has mentioned, that could be employed now with what we know. That's all. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yes, thank you. I just wanted to add on to [CLIAC MEMBER] comment about that there are existing models, and point out that it wasn't a governmental, at least as I understand it, organization that designates the level of trauma units. That's managed by the American College of Surgeons, who does those inspections. And that kind of comes back to the comment I had made earlier, that perhaps we look at how some other organizations may be able to augment that. And sometimes, frankly, these things get executed via the payers and whom they recognize as being designees. And to [CLIAC MEMBER] comment about registries, somebody has to manage that registry. So, who would that be? Would that also be perhaps some private organization? But anyway, I wanted to add to [CLIAC MEMBER] comment and just point out that it the College of Surgeons, not CMS, that manages that trauma level designation. CLIAC CHAIR: Thank you. CLIAC MEMBER: I agree wholeheartedly with the concepts that we're discussing here that I think it's very important to out the kind of good apples from the bad apples. I've seen the same thing locally with the kind of fly-by-night laboratories that pop up. I do think it's difficult, though, when we-- and it's important when we start discussing criteria for sorting out the quality laboratories, I think we all have a very good idea of what we understand to be a quality laboratory, but how do we quantify that if we say, oh, well, if you have a director that is board certified, well, what happens when we have a fly-by-night lab? We know it's a fly-by-night lab, but there's someone board certified at the helm. I think we need to be very careful when we start really thinking through our criteria for how we designate a quality laboratory. Because I think it can get a little sticky when you really get down to it, because we have a good idea of what a quality lab is, but we could really kind of get in the weeds there. And also, I agree that when you start looking at LDTs, all LDTs aren't created equally. You have your full homebrewed tests, and then you have some that are just an alteration of an existing test that is just adding a different sample type or a different cycler. So, it's not a full homebrew, but it does an LDT by definition. So those are, I think, very different approaches to the way that you perform that validation. Just a few thoughts that I had on how we approach our criteria. Thank you.

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CLIAC CHAIR: Thank you. CLIAC MEMBER: Thank you. I'm going to propose that we take a little different approach in looking at this. Maybe we should consider this as a lab section. So, you have your LDT section of the lab that's inspected as you do your normal inspection process with a checklist and looking for competency in this area. And in that way, a lab could then be certified to be able to bring on an LDT, and it would go through the normal inspection process. Something to consider. CLIAC CHAIR: Thank you. Great idea. CLIAC MEMBER: I promised myself I won't be the muted person. I believe Jennifer Ramie mentioned before something about-- I believe it was [CLIAC MEMBER]- looking for experts and not people within the government. And I think that's a very important thing if you look to the expert organizations, and for example, the CAP, and granted I do a lot of work with them. The CAP is allowed by CLIA to perform laboratory inspections. So, combining a few things that have been said before, perhaps adding a measure of complexity in terms of personnel, lab testing, proficiency testing that's performed, and types of tests are performed. And then creating a metric from that within the lab inspection that qualifies you as, to your level of complexity, and therefore the types of LDTs that you can develop. CLIAC CHAIR: Thank you. [CLIAC MEMBER] has noted-- she was wondering how best to share common themes for recommendation, and that raises, who wants to run the SharePoint? And I'm looking at [CLIAC MEMBERS], who are the most technical, if you all don't do it, Heather could do it. But perhaps [CLIAC MEMBER] could start by noting the commonalities that are coming out. While that is ongoing, I wanted to comment about some things I've heard. [CLIAC MEMBER] thinks certification is helpful. I think it is a first step. What I saw in this last year, where folks who may have been certified decades ago, who have never since been involved in clinical laboratory testing, but yet, by virtue of certification, would qualify for lab director. So that made me uncomfortable. In terms of certifying labs to be able to do LDTs, it's one thing to have the infrastructure. But I do know in this rapid scramble to get up and running, I was looking across the Bay at my sister institutions. And they took the CLIA lab director from their high complexity lab, consulted with a research foundation, where they were given $4 million to bring up COVID testing using the labor of 45 graduate students who could no longer do research because they were furloughed to bring up testing. They brought it up in record time. Those are the kind of resources that a laboratory which might qualify to take on an LDT, to which they don't have access, to be able to develop from the ground level up. And I mean, money and people, as well as scaling up the instrumentation. So, all of those are considerations. I see [CLIAC MEMBER] has posted her comments in the chat box. [CLIAC MEMBER] has made a comment about-- it would be necessary to have current and registration would be to be maintained for the ideas we've discussed. And then [CLIAC MEMBER] is saying something's wrong SharePoint because he got a dead link. [LAUGHS] CLIAC MEMBER: Yeah, apologies. I wanted to try posting this to our common workspace, but I am not able to get to it. CLIAC CHAIR: So [CLIAC EXECUTIVE SECRETARY], are you— CLIAC EXECUTIVE SECRETARY: I have SharePoint open. So, if you want to type it in to chat, I can type it into SharePoint. CLIAC CHAIR: So [CLIAC MEMBER] has typed it in, if we can just cut and paste it. CLIAC MEMBER: Now, [CLIAC CHAIR], I have a comment. CLIAC CHAIR: I'm sorry You comment while [CLIAC EXECUTIVE SECRETARY] figuring this out. CLIAC EXECUTIVE SECRETARY: No, I don't see it in chat. Unless she sent it to Heather directly. CLIAC MEMBER: I can send it to [CLIAC EXECUTIVE SECRETARY], I'm sorry. CLIAC CHAIR: OK, thank you. [CLIAC MEMBER] back to you. CLIAC MEMBER Yeah. I would suggest we be careful about just saying a high complexity laboratory is qualified for LDTs. I'm a blood banker, I've worked nothing but high complexity laboratories all my life. You would not want me to be developing a de novo test.

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CLIAC MEMBER: Yeah, and that's part of the reason I was trying to get around the idea, especially in the EUA situation. You wouldn't be able to stand up something that you have not already brought up in your current lab. And again, these are very preliminary drafts. I was just trying to-- it seemed like these were the most common themes amongst the group. CLIAC CHAIR: So, thank you. Now [ADVAMED LIAISON] has been foolish enough to volunteer that he can get into SharePoint easily. So, I don't know how we share that, and whether or not— ADVAMED LIAISON: I copied and pasted it in. I see Heather is— CLIAC CHAIR: Going to display? And is there a way we can see it? ADVAMED LIAISON: I think. CLIAC EXECUTIVE SECRETARY: I don't know if Heather's going to share it. I see she's working in there. So, if she can't share it, I can share it. CLIAC CHAIR: So, while we work on that, I want to just remind panelists the chat box cannot be viewed by the public. So, when you have comments, it's best if we speak them verbally. So, I'm going to ask [CLIAC MEMBER] to talk about all these great points she's put in the chat. CLIAC MEMBER: I just want to get back to the point that when I was speaking, I was specifically speaking about molecularly vetted, molecularly board-certified people-- or who were performing current laboratory developed testing. I mean, maybe there's a level above high complexity. I don't think high complexity as a chemist, or a blood banker, would apply. I think it would have to be something that the CAP could inspect, that eventually maybe CLIA could inspect. I just think that through the formal processes, it is going to be too slow if we have another pandemic. That's all. And I'm not suggesting that there wouldn't be other guardrails. Yes, there would be paperwork, perhaps, or online registration involved. I mean, again, to me the LRN already vets everyone and has a massive email of every laboratory in America. And it would be a big step, but somebody has to pop up a web page where people could apply to become these pandemic preparedness laboratories, if we want to call it that right now. We think that we have the expertise for doing this next time around and that network of laboratories, above and beyond the for-profit venture capital funded laboratories would be a part of the discussion and a part of the LDT deployment. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, going back to what [CLIAC MEMBER] was saying, and [CLIAC MEMBER], so you can have and this issue of if somebody is board certified. So, the lab complexity, that's a very difficult concept, but again, I'm going to just go again and be somewhat concrete. You actually can't be a high QT center, even if you had every last box checked. You have to have a certain amount of experience in the past and ongoing experience. So that maybe is a way to deal with the lab complexity issue because I think everybody, well we just heard several excellent points, that that's going to just be too difficult to work with. But I'm just pointing out to the team, is that really what we're saying, right? That you've demonstrated in this area past experience. And that you've maintained some level of competency because I'm not sure, Valerie, you made the point, but like, are you doing this now? And again, trauma would be perfect, right? You're the best trauma center in the world, but let's say your population totally changed over, and you just don't see those cases anymore. It's not appropriate to call yourself a high-level center. Is that right? Is that getting to where-- thank you. CLIAC CHAIR: Thank you. And just loose associating, because we're now talking into much more granular detail than these broad-brush strokes earlier. And a very granular way is to look at who subscribes to which proficiency test that uses the technology of what we need to scale up. And maybe that is the catchment to find. OK. CLIAC MEMBER: Yes, hi. So, I wanted to propose another CLIAC recommendation. Kind of taking a bigger step back and recommending that the-- we can wordsmith agency, which agency, but maybe do a survey to identify how other fields of medicine have addressed this issue of balancing expertise, professional responsibility, and accountability. Right, so, Dara had mentioned about the provider having the accountability of prescribing opioids. She was describing a situation where there is a facility, right, that has to meet certain requirements, both historic and ongoing. And they're really talking about the same thing as these core elements, right? It's accountability expertise and professional responsibility. So, I'm always one for suggesting if someone else figured it out, might as well steal it. How other fields of medicine dealt with this, and can we adopt something similarly? But first do the survey to figure out how they've done it. CLIAC EXECUTIVE SECRETARY: Can I make one suggestion related to that? Are you locked into the fact that it has to be done through a survey? Maybe a more general--

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CLIAC MEMBER: Survey, study, yeah. CLIAC EXECUTIVE SECRETARY: --requirement or gather information in some way. CLIAC MEMBER: Yeah. CLIAC CHAIR: Some agencies should gather information on other fields of medicine. --on, and then delete to identify. And I think [CLIAC MEMBER], what you and [CLIAC MEMBER] are both getting at, is not only possessing these minimum requirements of accountability, expertise, and professional responsibility, but were also relating to an ongoing track record of excellence. How do you get your arms around that? With the opioid prescription, while it is tied to the individual prescriber, there is a larger database that folks are monitoring to see who are at which ends of the spectrum, and apparently overprescribing, potentially, to give feedback to the providers. So where is that feedback loop if we were to implement something like this? [CLIAC MEMBER] wants to make a comment, go ahead. CLIAC MEMBER: Yeah, I think that, related to this, that I think we in laboratory medicine have probably done this specific thing as well as anybody, but I think the broader issue might be to look broadly at credentialing and privileging activities, because that's where there's an assessment of expertise. So, I just wanted to comment on that as we think about this. That's how the medical community broadly looks at it, but I think in terms of making it very structured, we probably do better than others. CLIAC MEMBER: Yes, I just wanted to speak to recommendation three, which I agree with. And I would like to speak to the process by gathering data. Would doing a meta-analysis or a retrospective study achieve the same thing as doing a survey? So that's an avenue of data collection and information collection. CLIAC MEMBER: Yes, it could be. I think we changed the wording to just be very broad and let the agency, or plural, decide how they want to gather it. Whether it be through a survey or through some other mechanisms. CLIAC MEMBER: OK because I do agree with that. CLIAC MEMBER: Yes. A couple of things I wanted to mention, to play devil's advocate, yes, there are physicians that are allowed to prescribe opioids, but looking at the analogy that we're trying to make, I don't think many of them are allowed to actually make the opioids. And really talking here about an FDA purview of making something. And perhaps our pharmacists have some thoughts on that. But I do think there is a distinction between prescribing and making something. And then a recommendation to specific subtypes. I wonder if we can just go ahead and land on the subtype that we're describing, which is de novo lab developed tests. I think where we're looking at is coming up with something from scratch, rather than making a modification. We had discussed it a little bit. So, we might be able to clarify recommendation two by stating that. And then I would suggest for the committee to think about, we're come back and spoke a little bit more about tests for identifying LDTs specific to infectious disease testing, but as long as we're fixing the issue, let's fix the broader issue and also look at de novo tests for cancer identification and diagnosis, which I think [CLIAC MEMBER] had brought up earlier. And so perhaps we need to decide once and for all, do we want to only look at infectious disease, or do we want to address the broader perspective of de novo test development for molecular tests, or for any kind of-- I guess it wouldn't have to be molecular, it could be serology, I suppose, but anyway-- do we want to look at the broader question of de novo development of tests for diagnosis? Just a thought. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yeah, I've got some questions on rec one. I'm not sure about the wording and I'm following the intent on this. So, do I understand this to read that if your lab already performs high complexity testing with an existing methodology, that you can add something on to that methodology without excessive paperwork or process? And I think my concern is, what is the methodology? What do you consider a methodology? Is TMA the same as real time PCR? Is probe based versus dye based, open platform versus black box? I'm not sure I get what this comment is really trying to accomplish, aside from maybe coming across a bit elitist. Like I could say, well, my lab does everything, so I don't need to be-- I have every problem and type of methodology in the world, so I don't have to answer to anyone. I think that's a dangerous line. So, I'd like some clarification on what the goal of this is. CLIAC CHAIR: I think it's for us as a panel to finesse so that the goal was clear. And what I'm hearing throughout this conversation is we're mixing and matching interrelated things, but we may need to splice them out into their own lanes. Number one really addresses emergency declaration. What do we want, what do we think is needed? When there's an emergency, rapid scale up is critical. Number two and number three seem to be more long-term things, some of which could be related to de novo, some which could be related to LDTs. So, there's some hairsplitting in there.

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CLIAC MEMBER: Yeah, I guess I'm thinking like, so if something says, well, I have a plan for fusion in my lab, but they only use the FDA cleared assays, they don't use the open channels. Does that mean they're qualified to all of a sudden just start using the open channel? I'd say no. They have no experience with that. So that's kind of what I'm trying to play devil's advocate on. CLIAC CHAIR: No, that's totally fair. OK, [CLIAC MEMBER], your turn. CLIAC MEMBER: Yes, and I definitely wanted to continue this conversation here that [CLIAC MEMBER] brought up. And that's sort of why, again, I think our main concern were these people who have never done any type of real time PCR and don't know anything about molecular contamination. So, I think that was sort of what I was trying to get as the barrier to entry. If you're not already doing a testing type that is highly complex and requires the same sort of analytical rigor, you can't just say, hey, I bought my Panther, and now I got a PhD who may have gotten their molecular certification 20 years ago and not done any clinical testing since then. So CLIA wise, I'm good to go. But rather to say in this emergency situation, saying a lab has to be previously established, at least in the EUA portion. Again, that shouldn't prevent anyone from standing up later on. But really, the main concern, and I think where a lot of people got confused in this, was really they couldn't tell the sort of pop up COVID testing site where someone was like, hey, I can get you a test, versus those given at University labs. That was sort of the general idea I was trying to get out with this recommendation. CLIAC CHAIR: And I would comment, I mean, this all gets to quality, which is our North star. And so back to [CLIAC MEMBER], it's one thing to just swap out primers, right? You got to test this, you got the whole workflow, it's just a primer, all the way to starting that from scratch if you're coming from a nonclinical lab. And the example was an environmental. CLIAC MEMBER: So, I mean, by bringing up the CLSI 12 quality essentials, I mean, I think we need to incorporate, obviously, the pre-analytical, analytical, and post-analytical. It has to be the entire life cycle, plus the ability to have this higher-level molecular expertise. I mean, and yes, I suppose it could apply to proteomics or other things. But for the most part, that's what we're dealing with right now. So, if we want to make a generic term for these high-level things-- but I totally agree with [CLIAC MEMBER]. I mean you can't just hire a brand-new person that just got their board never developed or designed an LDT in their life and say you're good to go. I mean, I think that we have the opportunity to define this and have-- I mean, one of the recommendations is really to come up with the checklist of things that we're trying to-- I don't want us to have to get into doing the work group's job, I guess. I'm just saying that some very high-level criteria that exists in most high complexity plus LDT-- I mean, a high complexity lab is not an LDT lab in my mind. And so, we have to kind of designate that as something different. And if that pre-exists in the circle of laboratory life, all the components, including the post-analytical and the reporting, then those are the kind of people that need to be performing them and/or need to be included. I'm not saying that a University lab with grad students couldn't do this, but somebody should be a consultant for that person. Somebody who's prequalified in a hospital setting ought to partner, as you mentioned, [CLIAC CHAIR]. I mean, I think the main thing is preventing people outside of medicine from thinking this is just easy, like popping up a real time PCR, easy peasy. And then the other pieces sort of don't get in the mix. So, I totally think that previous accreditation of some kind, previous expertise in this LDT molecular world, whether that's infectious disease or oncology or genetics or whatever. Think whatever structure gets put into place for the next emergency could be modified and/or adopted straight out for other LDPs. CLIAC CHAIR: Thank you. CLIAC MEMBER: Almost did it. Yeah, I would second [CLIAC MEMBER] comment, and I agree with [CLIAC MEMBER], who said that just being a high complexity lab is not good enough. Early in the pandemic, I was recruited to be a lab medical director for someone who wanted to come in. And aside from the fact I didn't have a lab, which was kind of preventing me from doing it, I also didn't have the expertise. So enough for that comment. As far as seeing what other specialties are doing, and [CLIAC MEMBER] may have comments as well, I had some contact with licensing a trauma center. And I think the American College of Surgeons is-- correct me if I'm wrong, [CLIAC MEMBER]-- the group that does some of that, and in one situation we had a particular situation where we were looking at them to accept accreditation and investigation. And my understanding is ACS will accredit a, for example, a high-level trauma center. But if they have a problem, they don't come in and investigate it. All they do is accredit it, and then they leave. So, it's a little different than, say, the college, which does both accreditation and also has a complaint investigation side. It may be the PT, I think you suggested that, [CLIAC CHAIR], that's a start anyway. At least somebody that's been PT for these assays, it's not perfect, but it might be a start. And finally, we talked about these other laboratories, and you know, we've had some difficult times on pre-analytic, post analytic, and clinical testing. But why wouldn't it be important that someone that's doing these high-level assays actually be testing people? I mean, it seems pretty basic that there are aspects of those assays that probably are substantively different than some of the labs we've discussed as outliers. And it would seem like maybe that's kind of a basic thing that we might want to consider. And lastly, at some point, it would be, I think, important, perhaps, if it's appropriate, for [FDA EX OFFICIO] to make some comments at some point in this discussion. He may have some great ideas that we haven't thought of if he's permitted to comment. That's all, thanks.

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CLIAC CHAIR: Of course, he's permitted to comment, but he hasn't asked in the chat box. Meanwhile, [CLIAC MEMBER] is lined up. CLIAC MEMBER: OK, I was flipping through to go over and see if I could focus on the slides, we saw earlier but you're too fast. I'm thinking about this-- we talked about LRN how we've got laboratories at different levels of preparedness and engagement to begin with. I think if we're talking about response to a pandemic, that what we want to do is have laboratories, just like an LRN, sort of prequalified to be able to run with this. it's not that they've done this weird thing, because we haven't seen it yet, but they know what to do, they know how to approach it, and so on. And whether it's a laboratory director who gets prequalified, or the director and the laboratory, or so on, I think that's sort of what we're looking at. Or what we're trying to do, because we want to make sure that whoever's doing it is prepared. Anyhow, I'll let my next person comment. CLIAC CHAIR: I like that comment. It's the concentric circles to address the surge. How many circles do you go out? And who's in which circle? And then [FDA EX OFFICIO] says he's willing to comment. FDA EX OFFICIO: Double muted, sorry. You should hear me now. I said I should comment because my name was brought up and the FDA was brought up. We still consider a legislative solution to all of this as being the most important way forward. And Congress really is engaging all stakeholders, and they're leading it, and not the FDA. We've just signed on to the fact that we believe that this is complex enough. There's a lot of the complexities that you've shared here today. I mean, I look back to when I opened my clinical lab at Duke and-- or, was asked to open my clinical molecular diagnostics lab at Duke. And I was like, woah, I've done great research work, but I've never run a clinical lab. So how do I do? So, I found mentors, and it was a huge learning curve for me to even run a clinical lab, let alone develop a new test. And then I was called on to do as well, because at that point, in the 90s, there weren't any-- hardly any FDA authorized tests. So, we felt the need to, in our team, to develop LDTs. So, I know those complexities. And I'm in complete agreement with the FDA that a legislative solution is the best. And that's what I can say, thanks. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, I'm curious, since [FDA EX OFFICIO] on the phone here. Do you have an idea of how many of the EUAs that you approved, or even looked at, were from these labs that we're trying to identify? How many of these that were created came from these labs that we're talking about today? Do you have any idea? FDA EX OFFICIO: Yeah, so we in our New England Journal of Medicine, a piece that Jeff and I published back in September, we did report on a study that the FDA did internally, looking at LDTs and compared them to kit developers and the issues that we saw with them. And the vast majority of the LDT developers, we had issues either with performance, and we did deny LDTs, or we had issues with the validation and design. And it was, I forget the exact numbers, it was something like 80 out of 120 that we-- or, the first 120 applications that we looked at. So we didn't look at things like, who submitted the test, whether it was an academic or whether it was-- we certainly can look at that-- or whether it was a reference lab, or whether it was a pop up lab that we hadn't heard of before. We didn't parse it by that. CLIAC MEMBER: Well, and that makes total sense, because we are still in an emergency. So, my question to all of you is, of course, we need to identify where the best places to get solutions like this. But why would you limit anyone that could come up with the answer and the right solution? I think what the FDA has been doing is exactly right. Why limit anybody in any lab to put together a solution. Because if they have something burning in their belly, and they are driven to get this done and help people, and then they don't have the right equipment or historical quality in the background, then you're limiting what could save lives. So I think before you spend a whole day on trying to identify facilities that need to be the only ones, or the ones we go to first, I think you need to think about some of these inventions and technology solutions are not coming from the brightest and the best. They're coming from those people that have the resources to do it, they have the knowledge, they have connections. So, I just leave that as a thought. Let's not limit the capabilities of everyone trying to deliver solutions. Yeah, there's always people that are going to cheat. They're going to take shortcuts, but that's why we have the FDA. And the FDA will evaluate, is this something we are going to take a chance at? FDA EX OFFICIO: We're seeing more than-- this is data that's probably a couple of months old, from the last I looked at all the data-- we see more than 3,000 SARS-CoV-2 EUA applications. More than 3,000. And the vast majority of them, not even counting the academic LDTs, or academic, or reference lab LDTs, the vast majority, we have never seen these developers before. And they have come in and they've really helped out. And the ones that we've authorized. The ones that we think are good, they've really helped out.

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CLIAC MEMBER: That's why we have Silicon Valley and that's why we have opportunity here in our country. I think there's other things to focus on that all of you can be doing, than trying to come up and limit the creative juices of the people that are in labs today. I just think there may be some other things to work on other than those. CLIAC CHAIR: Thank you. CLIAC MEMBER: Thank you. And [CLIAC MEMBER], you bring up a good point. Perhaps we need to clarify. My understanding is that we were defining a group that could go straight to development and did not have to submit to the FDA, not that we would eliminate people from submitting to the FDA, but to try to unclog, if you will, that pathway. And I guess, as we look at these three recommendations, should we clarify that what we're trying to address is the issues that were brought up by the two percenters from Mayo and the University of Colorado that-- when they got in some iterative EUA discussions-- And anyway, let's clarify the fact that we're not saying nobody else could apply to the FDA. Just that these are the folks that did not have to follow the same pathway. Can I get some clarification on that, please? CLIAC MEMBER: I can't imagine us not ever going to the FDA with anything. They've done an incredible job in a very hard time. I can't even imagine us doing that. CLIAC CHAIR: But I can imagine Dr. Binnicker's lab, Dr. Aisner's lab, going live with their assays, and maybe a retrospective FDA look at. But their track record of quality, I would trust them to bring up a quality assay. So that's kind of the hairsplitting we're talking about, [CLIAC MEMBER]. Proven track record versus brand new, out-of-the-gate, no experience, and then the spectrum in between. Oh, I'm sorry. I see all these agrees, and I don't see a comment, but I think I missed [CLIAC MEMBER]? CLIAC MEMBER: Yeah, I was just going to say there's a distinction to be made between the silicon slopes and Silicon Valleys of the world innovating and bringing disruptive technologies. No one's saying that that can't happen. But those people who may be software engineers, like a chemical physicist, should not be the ones directing the lab testing. I think that's the distinction that maybe was getting confused. They can transfer that technology to a laboratory that can then bring it on and operate under a CLIA umbrella with the right oversight and experience. And that definitely should be happening. But you can search in the news for what happened when silicon entrepreneurs tried to come in and sidestep some processes here in Utah. It was ugly. CLIAC MEMBER: Yeah, you're going to have those. But I'm not just saying just Silicon Valley. I'm just saying, as [FDA EX OFFICIO] has alluded to, there were thousands that were so helpful, and they didn't have all these credentials and recommendations. But naturally, they need to team up with experts that rule this out. I think it's almost impossible to do what you're talking about right now. If you identify five or 10 of these resources for the CDC to go to right away, or to work with, I mean, they partner with organizations like that all the time. But I think if you start limiting all of these labs from participating in the solutions, I think you're really cutting the knees off of our assets we have in our country. CLIAC CHAIR: So, I have [CLIAC MEMBERS] lined up. I'm also giving you a time check. It is 5:28, and this session is calendared to end at 5:40, with an adjournment at 6:00. My question is, we've had a lot of conversations going in many different directions. We have three recommendations on the table that are not well fleshed out, and I've heard repeatedly from [FDA EX OFFICO] that if we want to make a change, the legislative route is the way to go. And if we want to make a change, and we undertake the legislative route, we need some well-defined recommendations that we move up through the agencies and through the process. So, my time check question to you all is, we can continue the conversation, but will we, in the next 20 minutes, be able to refine these recommendations to move them forward? Or should we, as [ CLIAC MEMBER] recommended an hour and a half ago, should we convene a workload. So, with that, I'm going to have [CLIAC MEMBERS] then we'll come back to the question. CLIAC MEMBER: [CLIAC CHAIR], referring back to your statement, and were you referring to only situations where a public health emergency has been declared in regard to your comment? Or are you referring to any time a EUA type cast is created? CLIAC CHAIR: I have not thought that deep, [CLIAC MEMBER]. I'm thinking like immediate surge scale up, which is the EUA. And then I'm thinking in the background, things that are not as time sensitive. What do we want long term as the correct route for an LDT? You're rubbing your chin. If you have no more comment, I'm going to move on to [CLIAC MEMBER]. CLIAC MEMBER: Move on. CLIAC CHAIR: OK.

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CLIAC MEMBER: So, I'm going to propose some wording, because I think we're getting mixed up here. Nobody's trying to stop anybody from doing testing or applying to the FDA. Nobody. I'm saying that in a public health emergency, those laboratories that are-- maybe we should say, that are pre-authorized to perform high complexity laboratory developed tests, should not be required to stop their forward motion, is what I'm trying to say, while they go through the paperwork process, because they already know how to do this. So, they would have to be pre-existing, pre-inspected, have a set of requirements in place, and those people would just go and start the front-line testing. But anybody else who wants to come up with a new strategy or anything, any other combination, could go through the normal EUA process. That's all. That's all I'm trying to say, is that when we had people in the ICUs, and we couldn't get reagents and we couldn't launch our tests because the clinical laboratory and hospitals were not a part of the pre-existing conversation to prepare for pandemics, that's wrong. Because our people in the ICU can't get tests, but somebody on the street that wants to know if they have COVID can just send it into a laboratory that's sucking up the rare reagents that we needed at the beginning of the pandemic. So, let's just be clear, that in the next pandemic, there will be people hospitalized again. The front line needs to happen. And nobody's trying to stop any other innovation or any other entity doing testing, although the comment about Theranos was well taken. There's lots of people who think they can do this. So pre-existing authorization, high complexity that encompasses the full lifecycle of the laboratory tests, pre-analytical, analytical, post-analytical, and we should specify human and medical, in some way, shape, or form, because that's the labs we're talking about. Those are the labs that could and did deploy in two weeks. And nobody's stopping anybody else. And so, if that wants to go through CMS or that wants to go through FDA and the governmental process, if that's what has to happen, then that's what has to happen. But I think we need to be more nimble next time and still allow for innovation. CLIAC CHAIR: That sounds like two swim lengths, right? You already passed go; the other one you have to pass go. And [CLIAC MEMBER], I'm sorry. Your turn. CLIAC MEMBER: Oh, it's fine. No, I was just-- really more of a question in that, does it matter, really, what we're testing here? I mean, in recommendation one, it does talk about a public health emergency. So, I would take it that we're meeting something that is pretty serious, something that, I don't know, can kill you in three days. Or are we talking about a new laboratory developed test for, I don't know, cortisol, or something that may not take a lot longer to kill you or whatever? And so, are our recommendations based upon what it is that we're testing? Does that make sense? CLIAC CHAIR: It does. And it gets to the time sensitivity and the scale up, so you're right on point. CLIAC MEMBER: OK. CLIAC MEMBER: As a follow-up to [CLIAC MEMBER] thought, yes, I think that's why recommendation number one is very attractive. Because it's specifically a public health emergency. And so, we know when this is going to occur. And there's examples from past emergencies, like Zika, for example, where this could have been very helpful. One of the things, though, that I'd like to point out is I don't think it's good for this to stand alone. I think it needs to be linked to the Laboratory Response Network. So if we added a phrase here that says that these laboratories would then be recognized through the Laboratory Response Network, and a separate category of clinical laboratory, that would link it all together in a way that it's not well recognized now. Because your 25-bed hospital lab is completely different from your medical center developing a lab developed test. CLIAC MEMBER: Yeah, I just want to add to what [CLIAC MEMBER] said. There is already a system in place because of Zika that a lot of people are still not aware of, between APHL, CDC, and the commercial private laboratories, called the private public partnership that was dropped. An MOU exists on public record for this agreement. And we tried to deploy this during SARS and it questionably worked. Part of that was because of the deployment of that first EUA test not being as easy as we'd hoped. But at the time, when we started to get through the first few months, there was a discussion with the American Society of Microbiology. One of the things that was voiced was, a lot of large academic medical centers said, why is it just the commercial labs? Why can't this be broader? Why can't the large, really experienced molecular and regional centralized labs be involved? So, I think, [CLIAC MEMBER], maybe, if that gets wrapped somehow into the LRN, and there is a database where everyone is designated that has the capacity to answer the call like this, that's perfect. Because right now, it is the Quest, ARUP, LabCorp, Mayo. Because we were involved in their early work, but I think with SARS, that kind of showed us that there could be a much larger response, and it should be. CLIAC MEMBER: So, I'm in total agreement with the explanation from [CLIAC MEMBER]. Thanks. And so recommendation one, the only thing I would add to that, would be for the next steps on this recommendation, would be to request funding to support the development and research of identifying these specific labs, and implement this list during this pandemic that we're having right now. So urgently hold this group of labs together to be ready to support further needs of this pandemic or others. So funding is critical to identify and then list out who will be on this list.

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CLIAC CHAIR: Can I ask-- thank you, [CLIAC MEMBER]. Before the sentence, before [CLIAC MEMBER], you asked that these laboratories basically are able to provide the surge capability. So, in this sentence, what do you mean, as a separate testing category entity? Do you need to add a phrase to provide additional testing capacity? CLIAC MEMBER: I was thinking of the description of the LRN from Dr. Villanueva’s presentation, where the pyramid with the three sections in the clinical lab section is a broad footprint. I think that should be broken into different parts, whereas the bottom layer would be lab staff are recognizing and then referring to other labs. We would then have that separate to that next level being the clinical or commercial labs that are designated as laboratory developed test capability, so you would break that into parts. That's what I was referring to. CLIAC CHAIR: Thank you. CLIAC MEMBER: Do we think that CLIA or CMS, I should say, or FDA, even has the authority to make this change? Or are we saying, then, that this is a letter that would go to Congress? How are we thinking this is going to be enacted? CLIAC MEMBER: This would be a proposed request. CLIAC MEMBER: To who? CLIAC MEMBER: And a recommendation from this committee, from this advisory committee. CLIAC MEMBER: Yeah, to who? CLIAC MEMBER: Well, you're proposing it to the CDC, CLIAC MEMBER: Yeah, so I don't think the CDC, or the CMS or FDA has the authority. I think they are following the law under the emergency use declaration. But I may be uncertain on that. But I think that was going to have to be explored. It may end up being a recommendation you have to push to Congress. CLIAC CHAIR: I'll let [CLIAC DFO] add to this because he's next, but our recommendations go to the Secretary of Health and Human Services. That's our committee umbrella and then it from there somewhere else. OK? CLIAC DFO: Yeah, thank you. I think I'll leave to [FDA EX OFFICIO] if he wants to comment on the rules under which, and the laws under which, FDA operates. But I really do appreciate [CLIAC MEMBER] raising this question because it's unclear to me who you're asking to take action here. And I do think that if you send this to the Secretary of Health and Human Services, it's unclear what would happen with it. So that was my first comment. My second comment is, regarding the Laboratory Response Network, just to be clear, the Laboratory Response Network has not been responsible for the response to COVID-19. And so, I'll stop there. Over. FDA EX OFFICIO: And I can speak to that. OK, relative to that question. Yeah, I mean the FDA has tried to do things through guidance as it relates to LDTs in the past. And it was not an efficient way to go about this. And of course, guidance is not law. It's not regulation. And so, it can change and the ideal thing about legislative change is that it's set in law and it's really hard to change. So, these proposals going to the Secretary, the Secretary certainly can decide what to do with this information and can decide to forward it to Congress, if that's what they choose. But that's not something that FDA would do alone, we have limited opportunities to propose legislation from the FDA. If I could, I just want to make one sort of comment about a country that I've done a little bit of studying of in their response to the pandemic, and that's on South Korea. And they, of course, required authorization of all tests, but they didn't have a whole lot of tests that they authorized. And some of this has worked its way into the New England Journal of Medicine articles that Jeff and I have published. They authorized a small number of assays and then ramped up production. They also certified the laboratories that could run EUA authorized tests in Korea. South Korea based their EUA authorization on the US system. They saw that as good. One of the things that if you do that, if you select a smaller number of tests that can be run widely on open systems, and almost any lab that can handle molecular testing, you can ramp up testing much more quickly. Also, you can use the US government to make sure that everybody has-- you have efforts to ramp up the supplies, and you don't have competing interests. Now this isn't an all or nothing system, this is just something that you would have in the beginning and we would allow innovation and other pathways. But to use this as the initial support in pandemic would be great. You would have a more limited number, potentially, of developers of the actual reagents. You would have contract manufacturers set up to ramp up those production into the tens of millions. And you would have laboratories that would know ahead of time in the country what equipment would be great to have if another pandemic hits. And whether that is federally funded to provide that equipment to labs-- but one of the challenges in the US, is we had so many different assays submitted in so many different platforms in so many different ways that it took a lot of effort to make sure each of those OK. Focused effort, something that can be used widespread on relatively high throughput open systems, would be

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a way to ramp up. So that everybody, not just reference labs, can get access to accurate testing in short order plus. There's a sense South Korea's certified which labs could do the testing and a certification process just for the pandemic. Thanks for letting me make that comment. CLIAC CHAIR: Thank you. [CLIAC EXECUTIVE SECRETARY], you have a number of questions for us? CLIAC EXECUTIVE SECRETARY: Yeah. Due to the late hour, I probably won't ask them all, because there are a lot of different things bundled into this one recommendation. I see there are things here related to CLIA, there are things in here related to FDA, the LRN, and then the last piece about funding. But just noting the CLIA issues that are captured somehow in the very first statement, my question is, it says existing authorization to perform high complexity LDTs. Any laboratory that has a CLIA certificate and meets the requirements to perform high complexity testing could theoretically develop an LDT? So, there's no authorization under CLIA to specifically develop LDTs. And so that may need to be clarified before this becomes a final recommendation. Whether you're talking about some additional authorization, or if you're talking about any CLIA laboratory that meets requirements to perform high complexity testing. Other than that, like I said, there's a number of different things further on in the recommendations. So, I won't go into them now, they're not really my top area of expertise anyway. CLIAC CHAIR: Thank you. The hour is late, and [CLIAC MEMBER] has stated it well, I don't think the bread is baked yet. Which translates, in my mind, we've had a lot of conversation, we have a lot of ideas swirling around, but it is not crisp. And it is not defined and focused, what we're asking. So I'm curious, based on this single session, should we entertain the formation of a work group, or should we wait to see if the next two sessions pull out other LDT discussions, that we could then have a work group that would address items from all three sessions? Looking for panel members, of course. And no one's coming off mute. CLIAC DFO: I'll come off mute. I mean, I think this is a really difficult topic, obviously. I think it's been a great conversation. We are spending tomorrow, during the meeting, to continue the discussions around all the changes that have occurred during the pandemic. And from the regulatory point of view and an operational testing point of view. I would like to believe that tomorrow's discussion and presentations could help shape these recommendations, but also help determine whether or not you would like to ask for a separate work group to be established. So, I'll stop there. CLIAC CHAIR: Thank you, [CLAIC DFO]. What I'm taking away from this conversation and from our presenters, it seems that there's a cadre of labs who are able to respond quickly, provide high quality tests, and help in the surge and scale up, and they can do that very nimbly and quick. And what's the process around that as an LDT? And then there's a second group, less time sensitive, around LDTs in general. I'll just say the way this recommendation number one, with my pleural fluid cholesterol, yeah, I made up an LDT. But there's no way I would use that to justify, I can bring live a SARS-CoV-2 in February 2020. And so, I'm thinking if we're going to make a recommendation, we should split that hair and be very clear about what we're asking and how we can choose them. So given it is 5:51 your time, I would recommend we sleep on this and come back tomorrow and see if you have some brilliant ideas or word smithing. And keep this in mind as we go through. Can I have a show of hands, who agrees with me? OK, that's a majority, visually. [LAUGHS] OK. So, I want to thank all of you for all your expertise and your sharing. I want to thank the speakers for their very interesting, provocative thoughts. I want to especially thank [FDA EX OFFICIO], who seemed to be the target of a lot of the questions. And thank you very much for your collegiality. So, I want to comment, we will end today's session. I want to thank the public who participated with us. And we are ending day one. We will begin promptly tomorrow at 8:00 AM Eastern time. So, I ask you all to enjoy your night, see you tomorrow. CLIAC DFO: 8:00 AM Pacific time. CLIAC CHAIR: Oh, I'm sorry. 8:00 AM Pacific time. Thank you, thank you. 5:00 AM does-- I have problems. And for those of you who might have been curious, there is no virtual happy hour because we were a dud last month, so we're letting you go. Happy hour on your own. Thank you all. Meeting adjourned, day one.

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April 14, 2021 Call to Order/Roll Call/Meeting Announcements CLIAC DFO: Good morning, everyone. It is 11:00 AM Eastern time, 8:00 PM Pacific. And welcome back to the second day of the Clinical Laboratory Improvement Advisory Committee meeting-- or CLIAC, as it's known. CLIAC is managed by the Centers for Disease Control and Prevention and provides scientific and technical advice and guidance to the Department of Health and Human Services. The advice and guidance that CLIAC provides to HHS pertains to general issues related to improvement in clinical laboratory quality and laboratory medicine practice. In addition, the committee provides advice and guidance on specific questions related to possible revision of the CLIA standards. Because this is a federal advisory committee meeting, the Zoom chat and Q&A functions have been disabled for audience members. If you are experiencing Zoom difficulties, please contact CLIAC at CDC.gov. We will start with the roll call. I will call your name. And if you could just respond in some way to indicate that you are present and participating in today's meeting. Dr. Valerie Ng? DR. VALERIE NG: Here. CLIAC DFO: Dr. Birthale Archie. DR. BIRTHALE ARCHIE: Here. CLIAC DFO: Dr. Marc Couturier. DR. MARC COUTURIER: I'm here. CLIAC DFO: Miss Heather Duncan. MS. HEATHER DUNCAN: I'm here. CLIAC DFO: Dr. Mary Edgerton. DR. MARY EDGERTON: Here. CLIAC DFO: OK. Here's Susan Gross. Susan, are you with us yet? OK, we'll come back to Susan. Dr. Lee Hilborne. DR. LEE HILBORNE: Here. CLIAC DFO: Dr. Steven Hinrichs. DR. STEVEN HINRICHS: Here. CLIAC DFO: Dr. Jordan Laser. DR. JORDAN LASER: Here. CLIAC DFO: Dr. Thomas Lorey. DR. THOMAS LOREY: Here. CLIAC DFO: Dr. Lavinia Middleton. DR. LAVINIA MIDDLETON: Here. CLIAC DFO: Miss Carol Moss. OK. We'll come back. Dr. Nirali Patel. DR. NIRALI PATEL: Here. CLIAC DFO: Dr. Michael Pentella. Dr. Katherine Perez. Miss Jennifer Rhamy.

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MS. JENNIFER RHAMY: Here. CLIAC DFO: Dr. Gregory Sossaman. DR. GREGORY SOSSAMAN: Here. CLIAC DFO: Dr. Chip Watkins. Dr. Thomas Williams. DR. THOMAS WILLIAMS: Here. CLIAC DFO: Dr. Donna Wolk. DR. DONNA WOLK: Here. CLIAC DFO: Mr. Andy Quintenz. MR. ANDY QUINTENZ: Here. CLIAC DFO: Dr. Collette Fitzgerald. DR. COLLETTE FITZGERALD: Morning. Here. CLIAC DFO: Miss Monique Spruill. MS. MONIQUE SPRUILL: Here. CLIAC DFO: Dr. Timothy Stenzel. DR. TIMOTHY STENZEL: Here. CLIAC DFO: Miss Nancy Anderson. MS. NANCY ANDERSON: Here. CLIAC DFO: OK. So, let's see if I can't remember who all did not indicate that they were here. Dr. Mary Edgerton. Oh, no. You said you are here. Dr. Susan Gross? DR. SUSAN GROSS: Here. CLIAC DFO: OK. Good. Thank you, Susan. Let's see. Who else did we miss? Miss Carole Moss. Dr. Michael Pentella. Dr. Katherine Perez. OK. Did I miss-- did anyone else not indicate their presence? Might neglect— CLIAC CHAIR: Dr. Pentella. And Dr. Perez have just joined. CLIAC DFO: OK. Dr. Michael Pentella, are you with us? DR. MIKE PENTELLA: Yes, I am. Thank you. CLIAC DFO: OK. Dr. Katherine Perez, are you with us? DR. KATHERINE PEREZ: Yes, I am here. Good morning. CLIAC DFO: Thank you. OK. Miss Carole Moss, have you been able to join us? OK. I believe we have more than enough for quorum. So, we may begin. And OK, so members are reminded of the importance of remaining in attendance on both days, or today, at least, for the full meeting to ensure a quorum until all matters before the committee are addressed and the meeting is adjourned. So please stay with us. During the period dedicated to community discussion, participation is limited to CLIAC members only. CLIAC can only accept public comments that directly relate to the topics announced in the Federal Register Notice of the CLIAC meeting and as related to the theme laboratory medicine in the age of COVID-19.

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Today the committee will discuss and deliberate on the following topics-- first, application of regulations during a COVID-19 pandemic. And second, expansion of point of care testing, self-collection, and self-testing. Today public comments will be limited to a total time of five minutes per individual or group. If anyone in the audience wishes to address the committee, the public comment portion of the meeting is the proper forum to do so. Those who did not previously send a request for public comment and would like to participate today, please email cliac@cdc.gov as soon as possible to be added to the session. [CLIAC CHAIR], I'll turn it over to you. CLIAC CHAIR: Thank you. Copies of all PowerPoint presentations and other reading materials are posted on the CLIAC website. That is at cdc.gov/cliac. At the start of each presentation, I will announce the presentation number to assist you in locating the correct electronic filing. The blue number represents the presentation on the agenda. This meeting is being webcast by a Zoom webinar. Links for accessing the webinar are provided on the CLIAC website. If you are experiencing any difficulty with accessing Zoom, please email cliac@cdc.gov. This meeting is also recorded to assist in preparing an accurate written summary of the proceedings. A reminder to all of us that all of our discussions and deliberations must be available to the public. The chat box is not available to the public for viewing. CLIAC members, please do not engage in topic discussions offline through the chat box. Please use the chat box only to notify me of your desire to comment during the discussions of your desire to ask a question of the speaker. Now, moving into the meeting-- today's meeting session is titled Application of Regulations During the COVID-19 Pandemic. The first presentation will be from Miss Monique Spruill, who will present for CMS. The second will be from Dr. Timothy Stenzel, who will present for the FDA, and the third presentation from Dr. Ren Salerno, who will present on lessons learned from SARS-CoV-2 testing regulatory flexibilities. These are online presentations 11, 12, and 13. We have two public comments lined up-- one from Dr. Erica Andersen with ARUP laboratories, and one from Dr. Joseph Saad from the College of American Pathologists. If you wish to provide a five-minute public comment, please email cliac@cdc.gov as soon as possible. That introduction we will start our session. Miss Spruill, the floor is yours. Thank you.

Application of Regulations During COVID-19

CMS Regulatory Changes during the COVID-19 Pandemic Monique Spruill, CMS EX OFFICIO MS. MONIQUE SPRUILL: Good morning. We'll review the CMS regulations that were placed forth by our division. And I'll go on to the next slide also. This is a disclaimer slide. So, everyone can read this for reference. Just a little bit of what I will talk about today is actually the COVID-19 response and the interim final rule that we put forth, and also our enforcement discretion efforts that led to our public health response. So, the next slide, also. So, what we did was we actually really joined forces with the FDA and with the CDC. And we really wanted to make diagnostic testing available. And with that effort, we joined-- when we joined forces, it was with a tri-agency task force for emergency diagnostics. And this is how we really said, how are we going to respond to this public health emergency as we move forward? And once we joined forces, we wanted to really ensure that diagnostic tests were actually available. The next thing that we noticed was that the point of care tests were actually being released for emergency use authorization. And when these point of care tests were actually released, we also noticed that we wanted these to actually-- all these point of care tests-- to actually be administered by CLIA-certified laboratories. But as we moved forward, there was a term that we've all grown to know now. We had to address some enforcement actions with pop-up laboratories that these were laboratories that were actually not CLIA-certified that were actually administering these point of care tests. And so, the next steps we really had to use was actually looking forward to addressing these topics and issues. So, we actually went forth with stating that we were actually moving forward with looking at our cease and desist letters. And these were actually issued out to these facilities to tell them to please stop testing at this time. And those letters were actually issued out for all of these pop-up laboratories as part of our enforcement actions so it would be clear that only CLIA certified laboratories would actually move forward with actually performing these point-of-care tests. Another thing that may have been misconstrued by several individuals in the field was by manufacturers. They were actually marketing tests that were actually CLIA weigh tests. And with the marketing of these tests, individuals were confused that they did actually not have to acquire a CLIA certificate. And so, we actually wanted to respond to the community also to make sure that only these point of care tests were actually also being performed in CLIA-certified laboratories. I'm going to go on to the next slide, please. I think it moved. Another one of the immediate changes in processes that we needed to put in place was actually with our application system. We didn't want this application system to stand in the way. And we wanted to actually be able to issue out certificates as fast as possible. So, moving forward with our efforts, there was initially an administrative process. And then we would actually enter in this information. Or states would actually enter this information in. And then from the next steps

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behind it, once the administrative process was actually completed, then you would actually obtain a valid CLIA number, and also a certificate that-- a physical certificate prior to you being able to begin testing. And also, your CLIA fees would actually also have to be paid. So when we moved forth with this effort instead, it was actually once that application was actually entered into the system, in order not to delay any type of testing for COVID-19, this was one of our immediate changes that we put in place to say we would actually allow a facility to begin testing right away without having these administrative delays. The next thing that we received was-- and this was requested by our stakeholders-- that pathologists would actually be able to use temporary testing sites to actually review slides remotely. And this was-- this is just not for COVID-19 but for just making sure that the work that needed to be done during this public health emergency to take place and pathologists were actually able to use these temporary testing sites. And the next thing we really needed to do was prioritize our survey procedures. So, we really didn't want our laboratories to be delayed and having to prepare for surveys from CMS. And so, we had two different types of surveys-- our complaint surveys, process, and also our immediate jeopardies, which is also another type of complaint. We kept those in place, but anything like our federal monitoring surveys, those initial surveys, recertification surveys, and other items, we actually moved forward saying that you could actually delay that survey process so CLIA wasn't standing in the way in order to be able to respond to the public health emergency appropriately. And so, once that was reevaluated during the full response, we were able to move forward and just not delay any type of access for a public health emergency response. I'll go to the next slide, please. And another thing, we know that surveys are actually completely tied to their expiration date. So that's with the first bullet there. So, we didn't want to actually disrupt any type of laboratory processes. So, what did was making sure that we actually fully extended our certificate expiration date. And this is actually now on a later slide, also. But by extending these certification expiration date, we also went forward with also extending that survey process date. And so, this was just one of our necessary internal processes that we needed to put in place. And the next thing, we didn't want to penalize anyone that was not actually able to receive their proficiency testing. And so therefore, we postponed, suspended, and actually even canceled events. And we let our laboratory community know that they would not be penalized if they actually did not actually have proficiency testing that was actually being performed. The other thing that we wanted to do, we knew that our survey cycles and dates were actually being delayed. So therefore, we moved forward with our accreditation organizations being able to submit a plan to CMS headquarters. And once those accreditation organizations were able to submit a plan to our CMS headquarters, and that was an approved plan that could take place, and we wanted to actually keep everyone safe, that they were actually able to then go on and perform a remote survey. And this is a process that is still taking place at this time. And just to note, this is not a mandatory process, but it was an option that we provided our accreditation organizations to perform this remote survey process. And also, just moving-- just making sure that we were still responding to the public health emergency overall. Next slide, please. OK. And in September of 2020, we moved forward with placing an interim final rule. And that was put in place because we know that actually, having a reporting of our SARS-CoV-2 test results coming back into public health laboratories was actually necessary and needed. So, we wanted to be a part of this process and actually move forward. So we actually told all of our CLIA-certified laboratories that if they were actually testing and actually performing any type of testing for screening or diagnostics purposes for SARS-CoV-2 that it was necessary that they would actually be able to report. And normally, an interim final rule was used in the government. So, we can move forward with things rather quickly. And so, this was actually put in place. And then when we published that in the, Federal Register that publication date actually says, yes, this is the effective date. So that was on September 2 of 2020 where we actually moved forward with that interim final rule. I'm going to go to the next slide, please. And with this, a laboratory-- part of this modification is that a laboratory has to actually retain documentation of their reporting process, but in particularly, CLIA did not actually say exactly-- prescribe how that reporting process would take place. This was a very interesting time during this public health emergency response because we know one thing, that states and health departments-- what we just previously described there, that you were actually reporting both positive and negative test results. In all states, one of the lessons learned, of course, would be, all states were actually not able to accept the burden of having all of this data coming back over to them. So how is this reporting process-- and as you may know, formerly being a state employee, is that every data system is quite different within every state. So, our states came back and responded saying, please only report these positive results. But our CLIA-certified labs, when we first placed this interim final rule for, they came back with questions. And they wanted to know, well, if they're actually reporting over and if the states-- if they cannot accept all of their test results, we wanted them to know, no, you would not be penalized, that you only had to maintain the documentation that you were actually trying to report. And just one of the things about this reporting process is that this was actually really in response to the CARES Act. However, for HHS, they had set forth an additional reporting requirement. And so, when this action, this reporting requirement, was actually strictly written towards the CARES Act, and that the additional HHS guidance that was written after that. And so, this was strictly for our CLIA laboratories to report to public health and state departments, and strictly knowing that we wanted all the test results to be reported over. The next thing-- and that was without it being prescriptive overall. But if we go back and look at it now, for the history of certificate of waivedrs, they were actually-- that last point, that they were actually never included with a condition level requirement. And strictly right now we needed to move forward with actually including our

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laboratories and actually 493.2 for our laboratories that-- the certificate of waivedr laboratories, in particular-- into this reporting requirement, because prior to that, we would not be able to place any enforcement actions or move forward. So that's this last part, that our certificate waivedr laboratories were actually included in our condition-level requirements for 493.2. Next slide, please. And then this new reporting requirement was actually 493.41. And overall, historically, condition-- the certificate of waivedr-laboratories had only had to actually follow the manufacturer's instructions. And that's what we had always placed for. So that was their initial reporting requirement that, until this public health emergency, where we actually had now the COVID-19 reporting requirement that was actually added in. Another item there is that we needed to communicate very well. We know that with the 30,000 laboratories coming in and the high number of laboratories that were-- and now having 300,000 laboratories that the communication bases with our stakeholders that this new reporting requirement for our certificate of labor laboratories, that they actually needed to have this information. Let's go on to the next bullet here. We added a requirement for 493.55 C, looking at for our accreditation organizations and our exempt states that they actually had to also report to CMS that any of these condition levels for noncompliance of reporting, that that reporting had to take place within 10 days. And so that was another action that we took place that said, we have our condition certificate waivedr laboratories. And then we also had our accreditation organizations and exempt states. Also have the reporting requirement for noncompliance for SARS-CoV-2 reporting. Next slide, please. And this slide is in particularly for our non-waived laboratories. They were actually also added in here for an added reporting requirement overall. But what I want to really deal with for a second here is this second bullet, is that actually how we actually had to look at the difference between a primary sanction and an alternative sanction for our certificate of waivedr laboratory, and particularly here. Certificate of waivedr laboratories initially, they were only actually included in the for having primary sanctions. And what I mean by that is that their certificate could actually be revoked or suspended. So those were our two options prior to this. So, we actually had to make sure we actually moved over to actually having an alternative sanction. And so that's what that second bullet is that actually include our certification of waivedr laboratories. The third bullet there is actually now from that, when we are actually able to have those alternative sanctions, we were actually then able to-- if we wanted to go forth with imposing a civil monetary penalty. But I wanted to just outline what happens with our civil monetary penalty when there is a failure to report. For the first time that we're actually having our laboratories have a failure to report, then we're actually stating that now that we would actually give you a warning letter. And in that warning letter, we're outlining the conditions of our initial-- this says you have a reporting requirement and that this will be placed-- we've actually now issued out a total of 56 warning letters moving with this particularly requirement. And from that, the second time, upon revisit for a laboratory if we know they're not reporting, then we can actually impose a $1,000 civil monetary penalty. And then upon revisit after that, it will be a $500 civil monetary penalty too. We can close. So, I'm just going to recap that. The first time that they are actually not compliant for reporting, that would be the warning letter. The second time would be $1,000 civil monetary penalty. And the third time of actually upon re-visit, that would actually-- we can impose a $500 civil monetary penalty for not reporting SARS-CoV-2 test results. OK. Next slide, please. And we know that at this time, we did have a few tests that were actually being distributed out to nursing homes, and particularly to respond to SARS-CoV-2. So as we were moving forward, HHS, as they placed out these point of care tests for SARS-CoV-2 in our nursing homes particularly, this enforcement discretion would actually address this emergency use authorization for these point of care tests, and particularly in our certificate of waiver laboratory. So normally, like I said before, with certificate of waiver laboratories, they would actually-- yes, we say follow the manufacturer's instructions. And a few of these tests were given out where we received this feedback that they were actually for symptomatic individuals. And this was actually written into your manufacturer's instructions. So this enforcement discretion actually said, no, we would actually not fight you if you were actually administering this point of care test, particularly in nursing homes-- this is some of the feedback we were receiving-- if they were actually using this point of care test for asymptomatic individuals. And so, we didn't want to cite them as we move forward. And then this was actually initially for, like I said, our certificate of waiver laboratories. We then went on to expand this out to be any type of certificate. So you'll find the first frequently asked question that was given out for this particular manner was actually updated to actually say, yes, this is actually-- that actually uses these point of care tests for asymptomatic individuals, certificate of waiver laboratories, and then extend that beyond just those-- anybody not just with a certificate of waiver, for those laboratories. And that could be extended onto other certificates and not just for the point of care antigen test. And it was also extended beyond that for also with molecular testing. Next slide, please. And another-- this was actually one of our enforcement discretions for surveillance testing. CLIA wanted to actually be a part of the process where we knew that we needed to monitor outbreaks and we knew that this public health reporting had to take place. However, we did not-- the purpose of this frequently asked question was not to come back over and have reporting directly of presumptive positive tests or actually for inconclusive tests being reported over for any non-CLIA certified laboratory, particularly here. This was actually when we actually issued out an enforcement discretion. We only wanted surveillance testing, and this was particularly it, that they would actually be able to respond to the public health emergency. And actually, for tracing, tracking and outbreak purposes, contribute and have the laboratories or our facilities

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be able to contribute for surveillance testing for a non-CLIA certified laboratory. So therefore, we have provided clarification on this several times. We have also our COVID mailbox. And it's interfacing. And then from our lab excellence. And we get several questions regarding this. And so, we've always wanted to clarify that the intent behind this was actually never to actually fully move forward with presenting that presumptive positive or inconclusive test result. But instead that you would actually refer an individual over to a CLIA-certified laboratory for any further testing and that's all that would actually be stated to any individual. Next slide, please. The next two slides that I'll look at-- first here we'll look at non-CLIA-certified facilities, and then the next slide will be for a CLIA-certified facility. And particularly here. And this would be for variant testing, that if a non-CLIA certified laboratory was actually just reporting over any type of patient-specific test results to a state or public health department, then that would be fine, and that they could actually move forward with this strictly for surveillance purposes. But then at any time if they would actually report over and it's going to be intended for the use of diagnosis, prevention, or treatment, and if at any time that-- or for health assessment-- then this type of testing would have to be done in a CLIA-certified laboratory. But we did want to actually still have the option that where those patient specific results could actually move forward and be reported over to a public health department. And so those are just the clearly distinguishing types of activities that we needed to place forth in a frequently asked question for our non-CLIA-certified laboratories. And I'm going to move over to the next slide now after this. Now, this slide particularly is for CLIA-certified laboratories in that for our CLIA-certified laboratories, we know that you may have a limited number of variant tests when we started actually noticing that variants were actually coming back and being actually within a community. And we noticed that very specifically different variants were actually being transmitted into our population. And so, we wanted to not have CLIA stand in the way. So for surveillance testing purposes, that we wanted to say, if you're reporting back to state or public health departments, you would not actually have to establish performance specifications, but if that-- and also if patient-specific test results, they could actually be transmitted over to your public health department. And as long as you wouldn't have to establish those performance specifications, except for in cases if we're doing it for state and public health departments and the results are-- in particular, it's underlying. They're not intended for the use and purposes of individual diagnostic prevention treatment or the health assessment. And that's where we're seeing the difference is for surveillance purposes, you wouldn't have to actually establish those performance specifications. But however, if at any time those test results would be used-- and that's the second sentence just underlined there-- for individual diagnosis, prevention, treatment, or for a health assessment, then if that's occurring in a CLIA-certified laboratory, then the rest of our CLIA regulations would be applicable. And that would include conducting the performance specifications. Next slide, please. Here we want it to actually say for this overflow locations, a lot of us are actually seeing this where we're actually knowing that for a temporary testing site-- and particularly here-- is if there is a designated overflow location that a CLIA-certified laboratory that's primary holder could actually extend their CLIA certificate over to another CLIA-certified laboratory. And this is actually as long as two conditions were actually met. That first condition would be that the laboratory director was actually in agreement with actually extending this CLIA certificate over. And a second point would be, for that alternative site of testing that you could only go to an equal amount of testing that was actually being approved by the primary certificate holder. So, if a certificate holder has a certificate of waiver or anything else of that, they could actually only perform waived testing. You couldn't go beyond the certificate specifications. And particularly, we've noticed this with pharmacies and with schools-- for instance, CLIA would have been really overburdened trying to issue out certificates to every school across the nation. So, in this case-- and sometimes a school district might apply for that certificate of waiver. And that certificate of waiver could then be extended to other schools within their district. And so that was one of the solutions that we moved forward with our enforcement discretion. And this was well received. And we're still working with our state CLIA individuals and also working with our internal surveyors for both of these processes. And this has been well received. Next slide, please. And this is actually one of the things that we had to move forward with for our individualized quality control plans that underneath normal circumstances, they would not be allowed to be used with an emergency use authorization. And when an initial frequently asked question was put forth, this was still the case. And we needed to provide clarification and make other considerations after we considered some feedback from the stakeholder community. And particularly, we knew that the supply chain shortages and with the supply chain issues that sometimes these quality control measures that needed to take place. And also, with certain instrumentation that quality control measures actually were needed and that we needed to reconsider that frequently asked question. And so, what we did was we moved forward with-- that actually said, no, for ICP, it would be an option for an emergency use test. But in particularly, it was when it's classified as non-waived and when a manufacturer's quality control was actually less stringent than our CLIA quality control requirements. And so now ICP use is an option for an emergency use authorization test. Next slide, please. And particularly with this, we knew also that we-- because of the supply chain shortage, again, that we needed to actually really address this head on and make sure that CLIA was not going to be a burden or standing in our way. And so, we

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needed to actually just not have a response for COVID-19 reagents, but reagents overall that would be needed because of a supply chain shortage. And we also received some questions concerning this temporary enforcement discretion that said, OK, for some test kits that they received, that they actually did have a specific expiration date, and with that specific expiration date for some of these test kits, what exactly could we do and how would we move forward? And so this enforcement discretion was actually placed out in that we would actually have to classify at least one thing with this enforcement discretion that, if a manufacturer actually had an expiration date for their COVID-19 test, and particularly one of them would be by next now, that this enforcement discretion would not actually supersede that manufacturer's instructions. And so, this is still the case now. But one of the things overall, still just addressing this from the public health emergency, knowing that there were supply shortage and that you could actually move forward with using expired reagents or test kits overall. So that was the entire purpose of this. But, however, if the manufacturer actually did have an expiration date for their test kit, that we would actually not move forward with this. And particularly, one of the questions was for the next now test. I'll go to the next slide, please. And again, during this public health emergency, we just still wanted to make sure that we knew that certain states were actually behind and actually entering their certificate information. And so, the same thing I stated previously, but because the states were behind and they were backlogged, we wanted to say not having CLIA stand in the way. So therefore, in advance of being assigned a CLIA number that you would still be allowed to move forward during testing, and that in particularly, our last bullet there, anyone who was a non-CLIA-certified facility, that we would actually treat them as if they were operating underneath a condition-- a certificate of waiver and just make sure we were actually moving forward prior to receiving a physical certificate in the mail or that being transferred over to you that you could still perform testing and that you didn't actually need to be assigned a CLIA number at all. And this was actually received within the community-- stakeholder community well. And we're still actually-- still extending this enforcement discretion overall. And the next slide, please. And then our certificates-- we mentioned this previously-- that they are tied to the survey process being tied also over to the certificate expiration date. And so, we knew we needed to do more than that. So even currently right now, just recently, we extended our certificate date over to being June 30 of 2021. So therefore, this was extended over four years through the waiver certificate for your PPMs, your certificate of compliance, and also for your certificate of registrations and also for your certificates of accreditation. So basically, for all of our certificates, we wanted to make sure that by June 30 we were extending this date over. And we will still also maybe consider more extensions with our certificates, depending on how our surveyors are getting out and how our survey activities are taking place, and also as we receive responses from the stakeholder community, we will consider everyone. Next slide, please. What we wanted to do here now is actually look at all of our documentation overall for our guidance documents with the history. And so, this was actually made available to you. And the last slide is just our contact information. And thank you very much. CLIAC CHAIR: Thank you very much, Miss Spruill. That was a tremendous amount of work. Thank you for that excellent insight. Our next speaker will be Dr. Tim Stenzel talking about FDA regulatory changes during the COVID-19 pandemic.

FDA Regulatory Changes during the COVID-19 Pandemic Timothy Stenzel, MD, PhD, FDC EX OFFICIO DR. TIMOTHY STENZEL: Thank you. It looks like all my mutes are off, so you should hear me. If you could pull up my first slide, that's great. And I want to start out by really thanking our close federal partners at CMS and at CDC. Monique went through a number of incredible adaptions and demonstration of flexibility by CMS to deal with real-time issues. Oftentimes it's unfortunate that the FDA would do something and authorize something, and it would challenge our other federal partners. And we so appreciate CMS and CDC adapting along with us as we try to deal with this. And of course, we had other great federal partners. And I can't mention all of them, but I'll just mention some of the top ones. NCI, NIH, Florida, BEI, a federal contractor, and RADx, the RADx program. And together we certainly worked incredibly hard over the last year plus. And then Monique mentioned the tri-agency task force for emergency diagnostics. This was formalized in 2019, not too long before the pandemic. And I'm not sure if we met twice or just once ahead of the pandemic, as in a non-pandemic situation, we typically met in vision meeting, you know, twice a year. But obviously when the pandemic came along, we were meeting frequently and collaborating in between meetings and working with our other federal partners, as well, to make testing rapidly available. So next slide, please. I wanted to touch on some things that really help from the FDA perspective to make more testing available. It remains the cornerstone of our nation's fight. Vaccines are coming along, and that's great. There is some concern about variants and breakthroughs, so those variants and infections in folks who have previously been vaccinated or previously been infected, perhaps, with another variant. So, we don't see a near-term end to utility of diagnostics in this pandemic. And we are also making current efforts, some that I can speak about now, and others that are in the offing, to greatly expand screening in

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schools, workplaces, communities, and other locations, particularly screening those who are asymptomatic and still may spread disease. Next slide, please. So, I briefly mentioned this yesterday. This is a policy update in February 29, 202 when we wanted to rapidly expand testing and not have delays between when a test is validated and when it can be reviewed and authorized. So, this first policy update was targeted at laboratory developed tests. And we'd been hearing that labs really wanted to accelerate this. And we wanted to make this a possibility. And so, we-- on the trust system, we took notification that the lab had validated the test. We also asked that they confirm first five positives and negatives for a test that they had notified us about and report those results back to us, particularly if there were any failures, and then take any necessary steps. And then all the while, they worked on-- after they launched their test, worked on their yearly package and submitted that within 15 business days. That seemed to be well-received. And it is just one of those things that we did early on. Of course, we engaged with developers of all types early in the pandemic beginning in January, where we engaged individual developers from reference labs, academic labs, and traditional kit manufacturers-- in January 20 or more, and by the end of February, more than 100 individuals. And we also reached out through various networks, including ACLA and others, to spread the word and that happened in January. Next slide, please. And then one of the other things I wanted to mention was early on, there were no samples available, even as well past March 16. And so, we had a flexible policy that allowed contrived samples to be used. And a lot of the first EUA authorized tests and from labs, as well, were authorized based on contrived sample testing, and minimal at most of actual patient samples. And this also was a boon for test development. And then later on, as, unfortunately, positive samples became more prevalent, we did transition to primarily requiring actual patient samples in order to validate tests. On March 16, we expanded the notification policy, which allowed now kit manufacturers to follow the same pathway that we had given to labs. This, again, was a burden to test development and more immediate access to tests that had been validated. And notified the FDA while then they had a period of time to submit that test. And then we would review it. And all the time that we were reviewing, either LDTs or kit manufacturers could stay on the market and selling their tests in the US market. We also updated at this time that we were going to take a hands-off approach to serology tests. Serology tests had not been primarily of great importance in previous pandemics. And we thought that their access to them, however, could help with a couple of other important areas. One is to sort of track the infection, to know how many people had been exposed in our population over time. And the other was for research purposes, such as some therapies, vaccines, and other such applications where knowing serological stage situation for a given study participant and/or a potential donor for, say, convalescent plasma could access. In hindsight, as Jeff Shuren and I have stated in the New England Journal of Medicine piece on serology, this policy was flawed. We saw actors come in and, you know, I would say abuse this flexibility that the FDA had offered. They were making claims that we had not allowed in the policy. In fact, some of these tests might have been very useful for point of care or in-home tests. But we had not allowed under this policy that they were allowed to be used in high complexity labs only. And we saw that they were being used and promoted for other purposes and uses. And in fact, I believe we've signed approaching 20 warning letters for flagrant misbranding and marketing these tests that could be a point of care in either point-of-care settings or actually direct to consumers in the home when they had not been authorized for that purpose and it was not allowed under our guidance. So next slide, please. So, we did update our policy on serology. And then we did require our commercial developers at that point to make a submission. And that should be within 10 days of publication for those that had already notified or within 10 business days of a new notification. We then collaboratively worked with NCI to evaluate the performance of these tests. And unfortunately, the rate of denial or other such negative decisions for these serology submissions that did actually make it to us-- there were a lot that just stopped marketing, to our understanding. A large majority of these, I think their running rate right now is that those tests that made it to NCI that already passed some review at the FDA before they went to NCI paper reviews. But even so, 60% of them or so have failed testing at NCI. This does highlight for future pandemics and even what we can do in this pandemic to evaluate test devices in some of our pieces. Jeff and I spoke to how this might be stirred up in future pandemics. And in fact, outside pandemics where the government will have major testing. Next slide, please. We've tried to make information as readily available in addition to the town hall meetings that I spoke of yesterday in the form of templates, where we gave written recommendations. These templates could also be used to submit data to the FDA. We've launched a number of these templates and we've made appropriate revisions to them through time as updates were going to be helpful for either new types of tests or new applications, new sample types, or things that we needed to strengthen. Next slide, please. And of course, we talked about mutations yesterday and the notice in January on this. Next slide, please. And an updated policy that came out in February, which asks developers to get heavily engaged in monitoring performance. And the next slide, please.

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And then I sort of wanted to finish up on a screening topic, because it relates to the most recent guidance and pathways that the FDA has put forward. Surveillance is something the FDA has said that we're not going to be actively regulating during this pandemic. It is not intended to provide individual results. Largely it's at the population level. A screening, on the other hand, is focused at testing folks who are not suspected of having COVID and have no symptoms but yet could still carry the disease and give that to others who then could have untoward consequences. And then diagnostic is fairly straightforward. Someone has symptoms. What is the cause for those symptoms? Next slide, please. And so we provided in the last month a new pathway whereby a test that has been previously authorized and achieves either in the point of care setting or in the home setting at least 80% sensitivity and with a lower bound of confidence of 70%, that if they want to incorporate serial testing, we would advance their authorization. It would be a paperwork exercise. They would commit to the serial testing program at least once a week for molecular, at least twice a week for agent tests. And we would authorize them for screening purposes. We think this was-- what we've heard is it's greatly received. And we've already authorized several of these and in relatively short order. Next slide, please. And we've given a lot of supplemental information and a new template for this. And I've gone over a number of these. One of the asks though of those that follow this pathway is that post market they would validate their particular screening serial testing program and show to the FDA that it does mitigate the risk of false results. And then there is the possibility that we could revoke the serial testing asymptomatic screening claim if performance is not adequate. Next slide, please. And we've also provided a fact sheet about when is-- or what kind of test for screening. And I believe that's my last slide. And I can turn it back over to you, Valerie. Thank you. CLIAC CHAIR: Thank you very much, Tim, for your presentation and the heroic work you did this last year. Moving on, our next speaker is Dr. Ren Salerno and it's on the lessons learned from SARS-CoV-2 testing regulatory flexibilities.

Lessons Learned from SARS-CoV-2 Testing Regulatory Flexibilities Reynolds M. Salerno, PhD, CLIAC DFO

Dr. REN SALERNO: Thank you, Valerie. So, the intent of my presentation is to sort of summarize some of the things that both Monique and Tim have already mentioned, but really to try to set up the discussion for this particular session. So I will not be comprehensive in any way in terms of lessons learned, although I will try to highlight a few things that we've learned among hundreds of things that we at CDC have learned over the past year and three or four months. But I do want to start in the same way that my colleagues did, which is that probably the most important lesson that we have learned-- and surely that I have learned-- is the importance of our partnerships-- our partnerships within the government, as well as outside the government. Our partnerships with CMS and FDA have been absolutely critical every single day that I've gone to work since the pandemic began. I thought I worked closely with my colleagues from CMS and FDA before 2020. But I now realize how well I've gotten to know these people who are so incredibly impressive and have dedicated themselves to this response in an incredibly significant way. And I think we in the government, especially amongst us in the CLIA program at CMS and FDA and CDC, know each other much better now than ever before. And I think that will help us moving forward. In addition, partnerships across the NIH, BARDA, RADx, the testing and diagnostics work group at HHS have become new and really important partners for CDC and will, I think, for a long time have real benefits for the clinical laboratory community. Partnerships outside of the CDC-- APHL, ACLA, CSTE in particular, but all the clinical laboratory professional organizations, our clinical laboratory partners forum has provided incredible insight to at CDC about concerns, as well as ideas and suggestions for improvement. And we cannot overstate how important those partnerships are, both inside the government and outside the government. And we know we have lots of lessons to learn. And we need your help to improve. And we-- speaking for myself, I completely and thoroughly endorse the laboratory quality mantra of continual improvement. And you need others and colleagues to help you improve. And so, we're looking to CLIAC as well as our clinical laboratory partners across the country to help us through this crisis and help us improve the way we manage the system going forward. All right. With that, let's get started. Next slide, please. Probably one of the most important lessons learned, I believe, from this response, from a laboratory perspective, is this integration across health care and public health. And I know that sounds trite to say now. But more than a year ago, we at CDC were largely-- not entirely, but largely-- focused on our public health responsibilities and our public health partnerships. And we've learned with the expansion of testing and the demands on testing the importance of really strengthening our knowledge, as well as our partnerships and our engagement, across the entire health care system. And we need to do a much better job of thinking about that bridge, building a stronger bridge-- I think there was a bridge-- but building a much stronger bridge between the public health laboratories and the commercial laboratories, but the large academic clinical laboratories, and be able to-- as well as all of the other types of facilities, especially in point of care settings, with whom public health has historically had relatively little interaction. And yet, as we learned yesterday, point of care testing has become so much more important. And we in public health need to improve our connections and interactions with this broad testing community that's become so central to the response. Next slide, please.

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So, Monique mentioned this, I think. And this came up yesterday briefly. But the decision to allow laboratories to utilize remote sites for review of laboratory data and slides and images and to clear cases and report cases out, to sign out cases from outside a traditional CLIA laboratory facility, I think, was a major change, and something that was well appreciated by the community, and should perhaps be something that we think about extending beyond the pandemic. Next slide, please. You know, I think another really important change was the decision by CMS to allow CLIA certificates to be extended to temporary locations for testing, so not just for analysis of test results or test process, but for actual performance of testing in temporary locations such as parking lots, and really expanding the notion of a CLIA laboratory beyond the traditional four walls. This was especially important for expanding testing to under-resourced communities and to strengthen the response effort and broaden our testing coverage at a very critical time last spring and summer. Next slide, please. Monique mentioned this, as well. And I believe that this was really something brand new for CLIA to specifically engage in. The government was challenged in that the CARES Act indicated that test results had to be reported for all tests related to COVID-19. But it was unclear for a period of time what the mechanism, the regulatory mechanism, would be to ensure that those test results would get reported to public health. And the mechanism that was identified and was chosen was CLIA. And so, the CLIA program established a really brand-new requirement through CLIA to require the reporting of test results to public health and to establish penalties associated with not doing so. And so, I think this was a real shock and surprise for the laboratory community, and I think is worth consideration for how the CLIA program should handle reporting of test results to public health in the future. Next slide, please. And I think we've experienced this. And this is a pretty picture. And I think that the real picture looked much worse than this, because the government required reporting of these test results to public health and the CDC. But frankly, the infrastructure didn't exist to do that with the exception of a very-- some of the public health labs and a few commercial labs had set up electronic laboratory reporting to go directly to the state health departments and jurisdictions. But for the most part, these processes and systems didn't exist. And there was and there still is a lot of challenge around how to streamline this reporting so that it's not so burdensome. And in addition, the HHS came out with guidance in June that listed a large number of specific elements, largely demographic elements, associated with every person who was tested that was the responsibility of the laboratory to report with the laboratory test result. And so creating systems to integrate all of those criteria for test result reporting and putting all that responsibility on the laboratories who, in many cases-- perhaps most cases-- didn't actually have that data at hand has been a huge struggle for the community. And I think we in the CDC know that this particular problem is more CDC's problem than our colleagues in other agencies. And I think we are trying to work as hard as we can to really think about how to improve public health reporting from the breadth of the clinical laboratory community rather than, as we had in the past, primarily focusing on that reporting from state public health laboratories. Next slide, please. This has also been mentioned by both Monique and Tim. I do think it is an important lesson learned. And it was an important challenge for the community to kind of understand the new dynamic around certificate of waiver, point of care testing, and the specific expectations of the tests that were authorized for use in point of care settings. And the challenge around tests that were authorized for use on symptomatic persons but were allowed to be used on asymptomatic persons I think caused some degree of stress during the pandemic. And all of the three agencies have tried, I know, as hard as we can to provide as much guidance as possible to the community to help with this circumstance. But I'm sure improvements can be made in that respect, as well. Next slide, please. In addition, I think you've seen-- and hopefully you've seen-- a tremendous output of guidance and technical support from the three agencies in particular, as well as from others, to support all these testing expectations and changes in regulations, as well as just a focus on public health laboratory testing that we've never seen before in such a degree. And so hopefully this guidance has been helpful. I can tell you from a CDC perspective we sure have learned a lot about the need for CDC to be providing guidance in many different areas to support testing from many different perspectives, whether it's laboratory-based or point-of-care based or at home based, being very clear about what a nucleic acid amplification test is, what an antigen test is. And I think I would like to believe that we will be able to significantly improve the quality of our testing guidance broadly during peacetime so that in the next pandemic we will have much better information readily available instead of trying to catch up during the midst of the pandemic. Next slide, please. I wanted to spend a minute-- and I'm really grateful to Tim for raising the issue of diagnostic testing versus screening testing versus surveillance testing, because I think this is something that we, as a community, have really struggled with, in particular, during this pandemic. And I think we in the public health community thought the concept of surveillance testing was fairly clear pre-COVID-19. But obviously, it's not. And this article in the New York Times just a few weeks ago really demonstrated a challenge that we all have. And I think that this was sort of alluded to yesterday in the discussion about pop-up laboratories, but as Monique alluded, last summer, CMS offered enforcement discretion for some surveillance testing, particularly in University laboratories, to try to increase the amount of testing that was available to the

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country. And at that time, we were really struggling to substantially increase the volume of testing. But I think what this article demonstrates is that some individuals, some companies, perhaps people outside of the traditional clinical laboratory community, really misinterpreted that enforcement discretion to mean that if you call yourself a surveillance tester or you call your work surveillance testing that you were therefore not subject to the rules and regulations of CLIA. And we do know that there have been a number of companies that have set themselves up using surveillance in their company names and offered services to this article shows school districts for testing, which arguably is screening testing, because it's providing individual-- the individual-- it's conducting individually identified testing and providing results that are individually specified back to the schools for the schools to take action on those results. So, the facility is not necessarily CLIA-certified. And they weren't necessarily using an FDA authorized test. And so, it's-- again, I think this is not a-- I'm not sure that it's willful. I think it is a situation where it's confusing. And the community-- the broad community, especially everyone who is new to our clinical laboratory community-- is unfamiliar with or has been unfamiliar with sort of the technicalities of our industry. And that confusion has created some problems. Next slide, please. I mentioned partnerships earlier, so I won't spend too much more time on it, other than to say we've learned about the importance of these partnerships and the importance of building these stronger bridges across health care and from public health and back. I think we've learned a lot about the value of communication. Tim yesterday remarked on all of the outreach that he does personally, as well as his organization. Hopefully you know that CDC is also, since March of last year, been conducting very regular-- what we call clicker calls, clinical laboratory response calls, that as actively as possible provide information from the government out to the clinical laboratory community about the response. We've really used our-- what we call our LOC system, our Laboratory Outreach and Communication system, aggressively throughout this response to send emails. Thanks to CMS, we've been able to significantly expand the list of people who are on-- who receive LOCs messages. So, we have a high degree of confidence that at least the messages are reaching many more people now than they were initially. And we have received a lot of good feedback, a lot of questions as a result of these outreach sessions and town halls and LOCs messages. And what's great is that we've been able to collaborate with our colleagues, especially at FDA and CMS, to help promote decisions and policy measures that CMS and FDA have made out through the LOC system and our outreach calls. Next slide, please. So as a way of concluding, these are some of the things, of course, not all, but some of the things that we really want to work on going forward so that we're much better prepared for the next public health emergency. And I've mentioned improved communication across all sectors, a much better public health reporting system for enhanced surveillance that we really need to do a lot of work on in laboratory informatics, and a particular project that I'm really excited about, but I have been working on for many years and we haven't made much progress on-- electronic test ordering and result reporting to explicitly link clinical laboratories with public health laboratories in their jurisdictions. Better standardization of that public health reporting elements and expectations, enhanced capacity to perform testing at commercial and public health laboratories, I think we've achieved that. How do we maintain that over time, and better mechanisms that leverage all the new development and innovation that we've seen in the diagnostics community, as well as to enhance production capacity of those diagnostics? Next slide, please. So, in conclusion, I'm just going to leave these-- hopefully, we'll leave these questions up. But hopefully these will provoke a good discussion among CLIAC. These are the kinds of things that we thought could help stimulate comments. And of course, if you have other comments, we're happy to engage in those, as well. How have the temporary changes such as enforcement discretion in emergency use authorizations facilitated testing during the pandemic? What challenges have laboratories encountered in complying with regulatory requirements despite the flexibilities that have been put in place? Have the changes in regulatory requirements had any impact on laboratory quality and patient safety? Which of the temporary changes should HHS consider putting in place on a permanent basis through rulemaking and which changes should be reversed? And with that, thank you very much.

Public Comments CLIAC CHAIR: Thank you, Ren. We will now have public comment versus Dr. Erica Andersen with ARUP. Dr. Andersen? DR. ERICA ANDERSEN: Thank you. I apologize that I'm unable to share my video of myself. But I'll go ahead and read my comments. So, my name is Erica Andersen. I'm the laboratory section chief of cytogenetics at ARUP labs in Salt Lake City, Utah. Thank you all for hearing my statement today. At the November 2019 CLIAC meeting in Atlanta, I shared with this committee our experiences with the certification process for the home office sites of our remote working directors and technologist staff. This process was actually previously mandated by CAP with consultation from CMS and began for ARUP in the fall of 2018. And I'd like to share with you all today that there are still significant issues with how these regulations are being applied to aspects of cytogenetics work, which is being performed solely on digitized images at the computer and can be easily extended to home office sites. And many cytogenetics labs, including ours, employ remote staff to prepare the karyotype

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digitally and directors to review and verify these results. The process is being performed in an identical manner to those in our CLIA-certified central lab facility. So at the meeting in 2019, the committee issued a recommendation stating that when lab professionals are providing patient care through selection, interpretation, and reporting of patient results by accessing data remotely in a secure environment, they shall be deemed as performing those services at the primary site that houses the CLIA certificate. Since then, we and many colleagues in this cytogenetics community have been in a holding pattern waiting for a resolution of this issue. And so, I'd like to highlight some of the most pressing issues still facing us, along with lessons learned from the pandemic. So, first of all, working remotely-- as the pandemic began, a large portion of our workforce also began to work from home doing the same tasks as are being done on site. They log into systems physically located in our central facility using secure measures, including Virtual Desktop, VPN, and multifactor authentication. I want to highlight that no specimens or patient data are sent to, received at, or stored in our employees' home offices. And so, I feel like we've really demonstrated that the activities of cytogenetic analysis and result verification can serve as a fully functional extension of the laboratory. Since the CAP does allow certain remote activities performed via secure connection, if there's no CLIA certificate involved, we'd like to ask CMS to change its position on CLIA certification requirements for cytogenetics and no longer define the home office space as a separate laboratory site. Second, the process of actually obtaining and maintaining CLIA certificates has been problematic, primarily due to the CLIA inspection requirement. Prior to the pandemic, we waited for periods of months to over a year for the initial inspections to occur. And some of these are actually required before employees can start work. In addition, the process restarts any time an employee moves. So, every time somebody moves, we have to restart the process. And with 15 individuals approximately working for us, this has actually occurred a number of times already. And we just wanted to highlight the need for more work-from-home flexibility. Mobility is going to be a real need for support of our lab industry workers, and if the regulations remain unchanged, the burden is only going to increase. Third-- due to current requirements, our employees do incur serious privacy risks by having their home addresses included in the patient reports. Over the past several months, one of our employees has been receiving both postal mail addressed to their remote laboratory and spam calls from a call center asking about their CLIA certificate. And this is clearly a form of harassment directly tied to having our employee's home addresses on the reports. We recently learned CMS may allow for coding of home addresses. But in a previous written communication to us, CAP was explicit in opposition. And so, this requirement needs to be urgently resolved. Additionally, it's error prone, it impedes workflows, and it incurs a significant administrative burden on us. And then finally, because the maximum number of CLIA certificates a lab director can hold is five, this dictates how many remote technologists we can hire. And this has been a problem because there's a lot of individuals in the cytogenetics community that are looking for work but cannot relocate. And there's currently no distinction between the direction of a large clinical laboratory operation versus the home office. And so, if retained, we recommend to allow more than five CLIA certificates for these types of activities. So, in summary, we feel that the current position on cytogenetics creates significant financial and resource burdens with little to any benefit in improving safety and patient care. We therefore urge the committee to address these points by following through with their recommendation in 2019. And I sincerely appreciate your continued consideration and report-- support. Thanks. CLIAC CHAIR: Thank you very much, Dr. Andersen. Our next public comment is from Dr. Joe Saad from the College of American Pathologists. Dr. Saad? DR. JOE SAAD: Good morning and good afternoon. Thank you for having me back. My name is Joe Saad and I'm the Chairman of Pathology for the Methodist Health System in Dallas, Texas. I am here to represent the College of American Pathologists and appreciate the opportunity to provide comments to CLIA on the topic of application of regulations during the COVID-19 pandemic. Regulatory flexibility is needed to respond to pandemics. Since the beginning of this crisis, the federal response has improved with better coordination and alignment of regulatory changes. A swift process for relaxation of CLIA restrictions will allow laboratories the necessary discretion to determine what is best for their staff and patients during a pandemic. During the COVID-19 public health emergency, laboratories sought to employ appropriate protocols to reduce the risk of infection among staff while maintaining their ability to test and treat patients. The CAP specifically requested a temporary waivedr of CLIA requirements so pathologists and other licensed health care professionals could perform interpretations and sign out cases from remote locations.

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Furthermore, the CAP requested that the agency postpone inspections of accredited laboratories to allow personnel to devote the necessary time to fully verify and validate new coronavirus testing assays and to design operations to accommodate dealing with COVID-19 and to reduce the risk of travel during a pandemic. We are pleased that these requests were granted. But they may not have been were it not for the CAP and congressional appeals to waived certain CLIA requirements. As the CAP recommended during the October 2020 CLIAC meeting, once a public health emergency is declared, certain regulatory requirements should be waived or altered. For example, the FDA emergency use authorization is enacted upon the PHE declaration. A similar process should be enacted for the CLIA regulations in order to allow laboratories the necessary discretion to best manage their laboratory operations. Moreover, given the transmissibility of COVID-19 and in order to meet the demand for COVID-19 testing of patients, clinical laboratories established specimen collection drive through testing locations. While we welcome CMS providing flexibility on site locations, the waivedr was granted on March 26, 2020-- two weeks after the national emergency declaration, delaying critical testing. Importantly, while we support efforts to streamline administrative procedures for personnel, the CAP strongly believes that the current CLIA personnel requirements for testing should be maintained. The federal agency should collaborate and coordinate to ensure consistency among the respective regulatory guidance. For instance, clinical laboratories had difficulties managing the different COVID-19 reporting policy guidance that were released by federal agencies. The Department of Health and Human Services released the SARS-CoV-2. COVID-19 data reporting requirements on June 4. HHS, CDC, and state public health officials issued multiple complicated guidance documents that, at times, contained conflicting information. Consequently, clinical laboratories encountered a great deal of confusion and expended significant time and resources in attempting to understand and comply with new and confusing mandates. In addition, certain technical aspects of the requirements pose challenges and barriers to laboratory compliance. The requirements added multiple data elements beyond the actual test results to the data that laboratories must report. Many data elements are often not available to the laboratory in the information systems or within the scope of their operations. As an example, the guidance specifies that clinical laboratories must report to the Department of Public Health or the state or locale in which the-- or the state or locale in which the patient resides, regardless of where the laboratory is located. For many clinical laboratories, meeting these requirements will necessitate working with public agencies, and frequently, hit vendors to establish multiple systems interfaces. These processes are costly, laborious, and time consuming. To alleviate these challenges, consistent regulatory guidance is needed. Thank you for the opportunity to comment. And the CAP looks forward to working with CLIAC, federal officials, and the clinical laboratory community to develop solutions for COVID-19 and any future pandemics. Thank you. CLIAC CHAIR: Thank you very much, Dr. Saad. The presentations are completed and now it's time for-- CLIAC DFO: Did we just lose [CLIAC CHAIR]? CLIAC MEMBER: I think we did. CLIAC CHAIR: Thank you. Lost connectivity. I'm back. CLIAC DFO: You're back. OK, great.

Committee Discussion CLIAC CHAIR: Thank you. The presentations are done. Thank you very much for the public comments. It's now open for committee discussion. Again, please, if you could put your desire to talk in the chat, I cannot see your raised virtual hands. So [CLIAC MEMBER], you're first in line. CLIAC MEMBER: So, while this is just incredible to look back on all the work that everyone has done, my question would be to each one of you—[FDA EX OFFICIO} and to [CLIAC DFO] and also to [CMS EX OFFICIO]. We're still in the middle of this crisis. In each one of your areas, what were you missing and what are you still missing? For example, at the FDA, do you need more people to help you get these tests approved? For [CMS EX OFFICIO] at the CMS, are there limitations that you can think of, one major area that would have helped save lives during and in the middle of this pandemic now? And [CLIAC DFO], the same. Something has to stick out right now to you. If you had one ask, what would it be to help save lives and prevent this from happening further? What are you missing in your areas in the FDA and CMS and CDC? There must be something that we can start working on. FDA EX OFFICIO: I can start. So, we're at a much different place as the FDA, and I think as the federal government than we were not even that long ago. There's a lot more coordination of efforts with the current administration, which is very

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welcome. And you know, we're really looking ahead now at what isn't authorized and what is really needed to expand testing. And we're looking at primarily at high throughput, large volume systems or assays. We're looking at more than central lab testing. We just authorized one of those, the Thermo Fisher assay, that one instrument system. And it's not an uncommon instrument system. Can do 8,000 tests-- a single instrument can do 8,000 tests a day. And anyone in a lab could scale that up without a lot of extra headcount to really do high throughput testing. We're also continuing to look at, what can we do to expand a point of care testing and in-home collection and in-home testing? And we've seen a real flurry of activity and authorizations recently. We're still very active on that account. The prior administration and the current administration have been generous with headcount. We have been hiring like mad. But you hire somebody even if they come in saying with a PhD, they're unfamiliar with our processes of the FDA. So, onboarding is a critical part of that. And all the while, our regular non-COVID work has not slacked. Last year-- in the last year, we received 5,000 applications for 300 people in our office. And we're-- for the most part, we're staying up with the volume. And that's good. So, I really appreciate the expanded strategy tactics of the current administration. It helps us at the FDA and probably at the other agencies to understand, what should we be focused on? How can we work together? But a great question. And we can always use more people. I think that's the bottom line. CLIAC MEMBER: Thank you. CLIAC CHAIR: [CMS EX OFFICIO] or [CLIAC DFO], do you want to comment? CLIAC DFO: I do. I was waiting to see [CMS EX OFFICIO] wanted to say anything. I have something to say, but— CMS EX OFFICIO: Oh, [CLIAC DFO], you can go first. CLIAC DFO: OK. Thanks, [CMS EX OFFICIO]. Yeah, we need more people. That's sort of trite to say, I know, because I think that's true across the federal government, especially for those of us who work in public health, in the public health field. I mean, I think there's been-- it's obvious that public health has not received the historical funding that hopefully now everyone understands it deserves and needs. I think my one ask would be, and this alludes to something I mentioned in my talk, is I would love to see a health information exchange for laboratories, a meta cloud-based system that allowed all clinical laboratories in the country to plug into and seamlessly integrate their laboratory information management system with the public health laboratory in their jurisdiction to allow for a seamless exchange of test orders and test results within their jurisdiction and between public health and health care. I think that was a huge barrier to success was all the reporting expectations and requirements and challenges. And I think that-- I hope we'll be able to pursue that. I think it will take a long time to realize. But that would be my one ask of it. CLIAC CHAIR: Right. Thank you. CMS EX OFFICIO: I think from the CMS perspective, what we would want to do more is engage our stakeholders and engage with that laboratory community to where, if we're actually placing out enforcement discretions that there is an understanding and clarification to where we wouldn't have pop-up laboratories and they're able to understand exactly how we're moving forward. Another thing would be just regulatory action. As you place all this regulatory language, sometimes that can be also misinterpreted. So, writing things within plain language and communicating them over to where we have a clear, concise communication, and also with our partners, just having stakeholder calls and expanding that communication efforts forward so we're speaking one same message. I believe what was brought up was HHS having a guidance and then the CARES Act guidance and then what CMS was actually conducting at the same time. So if we join forces and have one communication effort to clarify rule language and also to clarify our enforcement discretions to where any schools or anyone else or more laboratory facilities are able to actually understand exactly the intent behind our enforcement discretions, this is one thing that I believe we can always do and we're going to look on doing better again in the future and now that-- still in the middle of the pandemic. CLIAC CHAIR: Great. Thank you. FDA EX OFFICIO: I agree with both those comments from [CLIAC DFO] and [CMS EX OFFICIO] and say communication with the community where the FDA has not traditionally communicated with them-- we found that there was a tremendous opportunity for education on both sides. And we think more communication would continue to bring harmonization, at least of thought, and understanding. And we would welcome them. Thanks. CLIAC CHAIR: Right. Thank you. CLIAC MEMBER: Yes, thank you. I wanted to bring up that there's another category of testing that we didn't really touch on. And that is blood product quality control. And for the convalescent plasma donors, we did a serology test-- not we, the laboratory that we would send out to-- and it became quite burdensome and confusing regarding reporting with BARDAS.

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By regulation, those donors had already been qualified by diagnostic testing as having had COVID. They would come to us, meet the criteria. And then we would do a serology test of each donation, which, by the relaxed enforcement discretion, could happen up to seven times. So there became kind of a blurry of if you've got to report it. And it was unclear whether it was CLIA or the state public health departments, who was really mandating it. So, it became quite the conundrum. And the same patient could be reported up to eight times then as having a positive result because of the seven donations that we were being required to report, as well as the original diagnostic testing. And I would suggest that the product you see really didn't need to be reported, since it was not a diagnostic test, nor-- not a primary diagnostic test being performed. So, I wanted to point that out and remind folks that there was this other-- albeit small but was pretty significant to the blood centers category of testing and reporting requirements that created quite a burden. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. In the past, we've talked about the overlap of CLIA with FDA device committees and the relationship with BARDA. And at some point, we probably want to explore that overlap. And this is just one of many indications. Thank you. CLIAC MEMBER: Yes. So, I have three comments. One is myself being a visual learner, there are visual learners and then there are people who learn from reading. And it's important when you present information to communicate with both of those types of learners. So, I find it easiest if I need to know how I need to set up a test to look at a decision tree. Do I have-- am I a CLIA certified lab? No. Do I have a certificate of waiver? Blah, blah, blah. And as things are updated, you can update the tree, but also have links to the specific PDFs and FAQs that address that so that you reach out to both the visual learner who quickly consumes the tree and the reader learner. And FDA seems to have come a little bit closer. But I wonder if there might be a consideration of enhancing some of our web communicate-- or some of the web communications from CMS and CDC. I want to say yes to what [CMS EX OFFICIO] said. I think it would be a great idea, and perhaps appropriate for a recommendation from us to set up a means by which an emergency communications office-- not appointed by the president, not politicized, with liaison to high population density settings that are at risk during a communicable disease pandemic such as schools, universities, factories. And maybe you might want to separate working facilities versus education facilities, that would provide answers such as, who can I contact? Who can do this? What can I do so that the 1.6-- what was it, million dollars that the Chicago schools spent wouldn't have happened, and so that people can easily find out where they can facilitate testing for an institution? The other-- and I think [CMS EX OFFICIO] started to say something about developing a communications office that perhaps would be activated during a pandemic, and therefore, would actually have the number of personnel, as [FDA EX OFFICIO] l pointed to the fact that, yes, we needed a lot more personnel. So, there would be an option for expanding personnel. Number two is on public health reporting. And yes, I want to say [CLIAC DFO] idea of common basis of public health reporting is really, I believe, what we should go for. With the 21st Century Cures Act, which is increasing interoperability between institutions-- so institutions, electronic health records, need to be able to send interoperable information. This may be a legislative thing. But I think it would be important as an extension of the 21st Century Cures Act to begin to focus on laboratory data. And as I recall from yesterday, there was a task force talking about data as a lab specimen. And I'm definitely a proponent of that concept. Data is the third arm of the laboratory-- anatomic pathology, clinical pathology, and then there's data, transfer of data. Data lives. And how data is transferred is very important. So, I think incorporating some concepts of the 21st Cures Act and thinking along the lines of more interoperability of laboratory data. And as the 21st Century Cures act itself covers CDAs, which are clinical documents-- I forget what the A stands for. Clinical Document Applications or something. The CDAs would cover the questions that the pathologist couldn't answer because the CDAs would be filled out in the patient encounter, whereas the labs could simply supply the data. But those could be tied together. And then finally I was introduced to the idea of the vulnerability that pathologists working from home may face if their address needs to be publicized. And I wonder if that might be achieved-- and this may not be our position to recommend this, but if I'm working from home and I remote desktop into my work computer, where am I really working from? Electronically, I'm really working from my work computer. And therefore, should my work computer's URI be seen as my address, not my physical address, because that's where my data is coming from? And that URI can be protected either by an appropriate firewall or masking one set of the digits so that-- because I'm sure publishing URIs would make people want to hack into it. But people get these URIs all the time and try to hack into them. So, there are already firewalls, and to a certain extent, protections. So perhaps looking at where the information is being generated as opposed to where the pathologist is sitting when it's images that we're looking at. And that's it. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I want to interject that your last comment around the remote site echoes what Doctors Andersen and Saad had in the public comment. And I want to note that in our CLIAC recommendations compilation, it's noted in our November 6, 7 2019 meeting that we recommended the CLIA program consider when laboratory professionals are providing patient care through selection interpretation of cardio patient results by accessing data remotely in a secure environment, they shall be deemed as performing those services at the primary site that houses

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the CLIA certificate. And the status of that is that this recommendation will be put on the agenda for the new CLIA regulations assessment work group that we heard about yesterday that has been formed for their consideration. And then as Dr. Saad noted, during the pandemic, CMS did issue a temporary allowance for this remote viewing. So, we see pieces of the puzzle started coming together and that the official change will occur with this regulation's workgroup. So, it's in process. In terms of the data elements, I just want to interject-- while we can certainly send the data we have, some of that data, I think, you were alluding to, and Dr. Saad did, which is the patient demographic information. We cannot achieve that. You're right. That has to be inputted at the time of order entry. Many systems allow that now or allow the abstraction. The nontraditional workflow group that we convened in 2019 came up with the recommendation with data as a sample. And that was actually related to, as an example, serum electrophoresis. The albumin and the globulin are done at one lab. The electrophoresis is done at a second lab. And the interpretation is done remotely somewhere else. And how is that data treated as a sample in the integrity preserved? So, as we talk about data transference, I just want to pop out that there are nuances to what we mean by "data" and if we can keep that in mind. OK. I'm sorry. Took up time. Next is [CLIAC MEMBER]. CLIAC MEMBER: Thank you. I'd like to start by thanking all the presenters. They were excellent presentations and did a really good job of walking me down memory lane of the last 15 months. It was a little painful. But I also want to thank you for all your efforts in all three agencies to make this an easier process. A lot of the things that you pointed out that have been accomplished has really made it easier on the front lines. So that's very much appreciated. I do have a concern about the number of CLIA certificates of waiver that are out there that will never be inspected because there are just not enough inspectors. And that really is a worry to me because I know that probably practices are not up to what we would like to see them in some locations. But it's hard to find that out. The other thing I wanted to point out-- and you touched upon this, [CMS EX OFFICIO]- about sequencing. And we have followed the recommendations of all the reporting to our health department, the results and sequencing. However, it has put us in precarious situations at time with submitters who want that information for their own knowledge, not necessarily that will change the care of the patient, because that will be communicated to them by the health department, but for their own educational knowledge of knowing what variant they may have been dealing with in some circumstances. So, we have been following the recommendation and deferring those questions to the health department. And that creates more work because people want to get the results from the lab that's negative. However, we don't see a way to bring an acceptable validation of the variants because you don't know what variants you're going to encounter. And we've been doing sequencing now for a good four years. But there's no proficiency test for it. There's no way to really comply with CLIA for that program. So, I wanted to point that out, that it's still an outstanding problem and every day there are problems associated with it. Thank you. CLIAC CHAIR: Thank you. CLIAC MEMBER: Thank you very much, [CLIAC CHAIR]. Just reflecting on some of the information we've heard in previous meetings about efforts from CMS to-- in their processes, changes come up and changes are made to their interpretation and enforcement of CLIA regulations. And I think it's come up with this committee before to talk about when would it might be appropriate and how difficult would it be to talk about a larger effort towards CLIA modernization, not just with specifics towards telepathology or specifics towards next gen sequencing or LDT, but a larger effort that would encompass many of these things, because we keep not-- I don't want to use the word band aid, but we keep seeing efforts towards modernizing a structure that's-- a framework-- that's aged well. But it is aged at this point from a regulatory standpoint. And I just wonder the difficulties we talk about in aligning in interpretation of issues around next gen sequencing and technology, maintaining safety versus flexibility in areas around point of care, the emerging technologies with the pandemic, as we talked about today. Is it appropriate for this committee to talk about making a more-- recommendation towards a more comprehensive long term just modernization of CLIA in total, taking into account all of these things that we've talked about and I think will talk about the point of care towards, again, personnel standards, next gen sequencing, telepathology. During this pandemic, we saw a huge push towards telemedicine, one of the things I think we talked about last time extensively with telepathology. We're not ready for some that with the CLIA framework. So just wondering about others' thoughts around that, and is there a possibility of-- and don't know what Ren and others would think about the difficulty of doing that and how-- and what kind of say this committee would have with something like that. Obviously, that's a legislative-- that would maybe be a legislative action necessary. But would this committee be willing to talk about and discuss a larger push towards that? Thank you. CLIAC CHAIR: Thank you [CLIAC MEMBER]. S CLIAC MEMBER: So, thank you again. Fantastic presentations. I want to pick up on the modernization theme, because that's a big-- it comes up every meeting. And it's something we all want, all of us. But one of the things in terms of modernization is communication. And we heard that in a few of the comments that preceded me, as well. It's always the

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central issue when things go sideways what a difference good communication would have made. And in the era, we're in now, one of the things that was really impressive was watching the communities communicate with each other, especially when the pandemic first rolled out. And whether you were lab or clinical, you were seeing things you'd never seen before. And the effort that was made-- we were all in contact with each other. One way or the other, we were reaching out. And perhaps some of you may have had a more organized way of doing this. Social media was remarkable. And there was nobody posting any personal private information. But there were groups that were coming up everywhere of certainly at least physicians just reaching out. Have you seen this particular find-- lab is the same, right? We're seeing things we never saw before and needing help. So I just want to perhaps emphasize that if we do look for modernization, if there would be a way for us to use all the tech tools now available for everything else-- what's more important than health and lab?-- to have some kind of system in place to aid in that communication. The tools are there. And that would be just something perhaps to think about, where we go first. CLIAC CHAIR: Thank you. CLIAC MEMBER: I want to echo what [CLIAC MEMBER] point was, and that to the agencies that this is the best time ever to put your requests and needs on the table. In 30 years, I would have never expected that laboratory testing would be the lead item on both national and local news for over a year. And so, our currency is unlikely to be ever higher than it is right now. We're the Bitcoin of the world. So, we've got to get this thing moving ASAP. And back to your point, [CLIAC CHAIR]- I guess my question then specifically is, do we need to enhance the previous recommendation regarding remote use or availability or allowance and expand it to such things or make it-- extend it to everything, including cytogenetics? Do we need to expand that recommendation would be my question back to you, or in the way in which it is going forward to the combined committee? Is it broad enough that they know it isn't just pathologists looking through their microscope or looking at a TV screen? Thank you. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. You just set me up. And I was going to bring this subject to bear, because [CLIAC MEMBER] has commented on the side. You know, [CLIAC DFO] had a list of questions. The first one was, in this natural experiment we did last year, is there something that came out of it that we should just keep? And [CLIAC MEMBER] brought up yesterday the issue of remote access, remote reporting. And it all ties into me with this workflow, non-traditional workflow model. There are a lot of things that can be done remotely that are bigger than just images. And so, laboratories are doing this. And back to [CLIAC MEMBER], it's the development, but rapid development, of informatics, platform, artificial intelligence. We've touched on this in previous meetings. The question is whether or not the current CLIA framework will allow that through a mechanism other than rulemaking or legislative change. And then secondly, in the natural experiment about remote access, are we as a group willing to recommend that we would request CMS to permanently allow remote access for all activities of a laboratory that can be done remotely? So, I'll just throw it out there and let you all jump in. I'm sorry. So, [CLIAC MEMBER] brought up yesterday in this year of experimentation, what were the quality issues? What are we not seeing? We're seeing the good part. [CLIAC MEMBER] says she is not aware of any unique quality or patient safety issues related to remote review of lab resulting because of the way that includes images. Do we need any kind of formal evidence to support that position? CLIAC MEMBER: So in response to what you just mentioned [CLIAC CHAIR], I would also state this meeting, this quarterly meeting or this half year meeting, is another example of what we need to get formalized, that we can operate in this way over video teleconferencing ongoing so that we don't miss a meeting like we did the last time. CLIAC CHAIR: Thank you. Does anyone else want to jump on the bandwagon to permanently implement remote access? CLIAC MEMBER: Madam Chair? And I would just like to join in. I support that comment, as well, because I did note that during the report, it was reported immediate process changes, pathologists could utilize temporary testing sites for remote review and reporting of slides and images, et cetera. And I guess I'm concerned or interested from the perspective of, this would increase the point of care testing and the rapidity in which information could be shared with the providers in order to engage in more timely care and intervention. CLIAC CHAIR: I'm sorry, [CLIAC MEMBER]. Was that a question or a statement? CLIAC MEMBER: Well, it was just a comment that I was supporting that I'm in favor of the more remote access. CLIAC CHAIR: OK. Thank you. CLIAC MEMBER: So, the CAP has guidelines for whole slide imaging adoption as a-- for being able to use post-slide imaging for analysis, which would be remote viewing, validation of post-slide imaging. So, I think it would be appropriate to point to different sources of validation and recommend that they be used.

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So, I'm, of course, as an anatomic pathologist, familiar with whole-slide imaging. But I would guess that there could be some developed for cytogenetics, which is a little different from imaging in H & E in terms of the resolutions required and so on. And I think to either ask a professional organization to provide guidance for CMS to point to existing guidance and maybe request more would be appropriate in terms of moving forward with this concept of working remotely and maintaining quality. CLIAC CHAIR: Thank you. [CLIAC MEMBER] has chatted me in the chat box. And I would consider— [CLIAC MEMBER] I'm speaking for you-- consider pushing the envelope even further. His comment is maybe we need to make this permanent-- that is, remote access-- absent any evidence of quality concerns. So, we don't know what we don't know. What we do know indicates there is no other quality concern. I'm going to step out of this and let [CLIAC MEMBER] make his comment. CLIAC MEMBER: It reminds me of the issue of trying to take a paper form and adopt it to the internet. Let's just kind of-- let's get started over again. I don't recall or know what the issues were that prohibited remote viewing in the past or why the rule was put out there. And so, let's just say, as you just did, that this needs to be made permanent. The technology has changed. It's totally appropriate. And it is no different than one of our people mentioned. It's using your primary computer from a different location. There's nothing special or unique to that. So, I would be very strongly in favor of us recommending that it be made permanent, but not just for digital imaging or anatomic pathology, but for all aspects of the laboratory interpretive process. CLIAC CHAIR: Thank you. I agree with you, [CLIAC MEMBER]. Somebody correct me. My fractured view of this is in the original inception of CLIA certificates, they were tied to a physical address. And so that was what started the remote licensing. But the advent of technology, VPN tunnels, and be able to remote access seamlessly sort of drove it to the decision, can we use the primary site as the CLIA site as long as the remote sites have verified their access faithfully reproduces what they're looking at? And on the lab side, there are so many things-- platelet aggregometry, neuro analysis, hematology, lupus anti-coagulant interpretations, et cetera. And now [CLIAC MEMBER] is tired of me talking for him, so now he wants to talk. CLIAC MEMBER: Well, I think I echo what's been said. But I think you sort of alluded to this. In general, CLIA is quite old right now. It preceded the internet. It preceded Zoom. We would never have had this meeting in this fashion had it even been a decade ago that this happened. And so, I think that the modernization is clearly in line. I think we need to look at all the things that the presenters that did an excellent job of showing the discretionary changes, all the things that actually happened, and really evaluate and make sure there were no quality issues. I'm not aware of any, either. In fact, I think in some ways some of the quality was actually better because it allowed people to be more responsive and so on. And some of the other assessments, the whole NGS assessments, as well-- not just the traditional, but even the emerging diagnostics-- can lead themselves to some of that. So, I think we do have incredible-- both internal government as well as accreditation organizations that are providing specificity and guardrails around these things. And I think we should really respond to that. I think we've heard them ask for that. I think that the practitioners want it. So, I'm just interested to hear the ongoing discussion. And hopefully we can move forward. Thanks. CLIAC CHAIR: Thank you. I want to comment about how imaging has helped in a very unusual way, and back to [CLIAC MEMBER] question around point of care test. When my point of care sites can't figure out how to interpret the card, they will take a picture of it and send it to me and say, is this positive or negative? I mean, so it's a two-way street. And the technology has advanced that. I have a question. And I'm sorry that I didn't give anyone time to prepare for this. It would probably go to [CMS EX OFFICIO]. So, letting her take a deep breath. Is there a way to incorporate some of these recommendations in the CLIA surveyor's instructions which would allow rapid implementation in the absence of going through rulemaking or stat sheet change? So, for example, to licensure issue-- a remote work would be tied to the primary CLIA license. CMS EX OFFICIO: I think one thing, moving forward with a lot of these recommendations go to our regulatory assessment work group. And that's the methodology we like to use to prioritize the modernization of our regulations, first of all. And yes, the majority of these action items would actually require regulatory changes. But if you have any specific questions, we can get back with you and let you know specifically which ones would and would not. But everything you've mostly mentioned, I would say yes. And that regulatory assessment work group is going to be a great tool for us to be able to hear and prioritize any changes that we need to make and know the exact modernization questions and methodology we could maybe use and recommendations to move forward with actions. So yes. That's a great question. I thank you for it. CLIAC CHAIR: Thank you very much. So, [CLIAC MEMBER], back to your question. That's what it would take. We would come with recommendations, lob it to CMS, and have them run in through the regulatory process. Next in line is [CLIAC MEMBER] and then [CLIAC MEMBER].

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CLIAC MEMBER: My comment may be starting to get redundant. But I do think it's important to note that the concept of remote work and the technologies of today, and like you said about VPN tunnels and such, the laptop that is currently sitting in front of me in my basement is the same laptop that would be in my office at ARUP that I would look at the same digital slides for parasitology to save myself a quarter mile walk up to the lab. So, I mean, if you think about it that way, there's absolutely no logic to some of these technology, archaic guidances. But I would stress that we can't advocate for an uncontrolled change. I mean, in lab medicine, we're all about controls and quality, right? We can't just add it to any screen because there are resolutions and refresh rates that do change interpretive abilities of an image. So I do think that there does have to be somewhat of a thought out process if this is going to be modernized that CLIA maybe has to give guidance on what the standards are for the screen they're using, the computer they're using. Is it your IT department or your quality group actually approving that versus just saying any screen? CLIAC CHAIR: Thank you, [CLIAC MEMBER]. In the non-traditional workflow model, we talked about having your device certified or whatever by IT and locked down security-wise and all of those elements, and that that would be the responsible of the primary site. OK, moving on— [CLIAC MEMBER]. CLIAC MEMBER: Yeah. I just wanted to make a quick comment that I really appreciated the FDA's emergency use authorization management in keeping us informed very quickly when those EUA's are being granted. When we were looking at convalescent plasma donors, they had to have documentation of their diagnosis. And we saw people coming with reports from laboratories that we questioned. And having the EUA information is easy to access and promptly updated, as it was. It was very useful for us. I think it was useful for other rural hospitals evaluating where they would get test results from. So, looking at the things that worked out were the technology emergency use authorization I thought was managed well. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yeah. So I just wanted-- akin to what [CLIAC MEMBER] rightly said about digital imagery and things, I would make a recommendation to add to that the PHI and have CMS pull in somebody from-- familiar with the HIPAA law, because if you don't have the data security, if the organization can't apply the same data security to a home station, which they all should be able to, that has to be laid out, as well, I think, as that it's the same data security as on the hospital campus. And maybe that was covered before. But I think that would have to be discretely defined, otherwise people would just work around those pathways, I think. CLIAC CHAIR: You're right, [CLIAC MEMBER]. The horror stories were around people in the airport with their laptop open doing HIPAA protected work, totally viewable by any passerby. [CLIAC MEMBER], you're next. CLIAC MEMBER: Yeah. Well, first, I kind of got the sense that you wanted to go around the room looking for support or lack thereof. So just for the record, I absolutely support the continuation of this remote work. [CLIAC MEMBER] kind of took what I wanted to say to kind of add on to [CLIAC MEMBER] comments, which-- CLIAC MEMBER: Sorry, buddy. CLIAC MEMBER: No, no. No problem. Great minds, right? Again, just focusing on screen quality and HIPAA and data security. And even like what Marc said, I think we have to be careful of being too prescriptive in any kind of regulation or guidance. I think what Marc had suggested in terms of having local IT and local quality being able to set those local standards for the use case and it being documented locally in the laboratory as to this computer is with this individual's able to do this work remotely. Because you don't want to open up the doors so anything can occur. And again, as my comment-- to my comment from yesterday is we might as well steal from other fields of medicine. Radiology has done a lot of this already. So, we don't have to look too far to get some good guidance. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I'm not hearing any violent objections to this conversation around remote access, just a comment that this is on the agenda for the new CLIA regulation assessed network group. And we heard yesterday that group is going to meet June, July. And there are at least 30 people participating. So that process is already in action. And I would suggest we move on and talk about these other questions that Ren has put forward to us. What are quality concerns we might have stemming out of the relaxed requirements? And which, other than remote access, that we talked about, should HHS consider putting in place on a permanent basis through rulemaking? And which of these discretionary items should be reversed? And I'm assuming Heather-- yes, Heather is working the SharePoint. So, you all don't have to fight to get on and fight over who controls it. I would like to just capture the remote access discussion that we talked, and we are in favor of it and we know the process to consider that is already in motion. That could just be of note. But I want the committee to look at the other four bullets. [CLIAC MEMBER]?

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CLIAC MEMBER: Yes. In relation to quality, I would just like to echo the comments made by [CLIAC MEMBER] about concerns regarding the number of certificate of waivedrs that have come about and how we ensure that those are being performed in a quality manner and the burdens that that places on CLIA. And again, do we really understand what that-- how that impacts laboratory quality? CLIAC CHAIR: I would like to make a comment about-- I think it's absolutely wonderful about this tri-agency task force for emergency diagnostics. I was relatively ignorant about it. I think it's absolutely wonderful. The question is, they were meeting twice yearly. Does it need to be more common? And then how is that communicated? I got brief wind about the roles of BARDA and EMS, emergency management-- I'm not sure what the federal name is-- as I learned my partners to get through the supply chain issues were much larger than the clinical laboratory community. And I would love to see how that working group could be enhanced, not only for the current pandemic, but to rapidly respond to the next one. [CLIAC MEMBER] has a comment. CLIAC MEMBER: Yes. So to that end, we've spoken about this several times, but it's my understanding there are no hospital representatives except those large for-profit-- or sorry, not-for-profit laboratories that are affiliated with a hospital or the for-profit venture funded capital laboratories who happen to own a hospital that are not in a large number there. So how will we-- I mean, there's integrated delivery hospital systems and individual large hospitals that I believe need to come to the table and bring that knowledge of the large hospital, the community hospital, the 50 bed hospital, and their clinics to play, because those are the front line people. And those are the people that were, we've said, a few times ignored, to some degree, during this pandemic, because all the pre-planning and the tri-agency planning did not include hospitals who were and will continue to be the first place that sick patients go with the next pandemic. So somehow, I don't know if we can make that recommendation. But hospitals cannot be left out this time. I think that the tri-agency is important. APHL representation, hospital representation-- as many people said, we all have to be connected and have access to information. And I think that everybody has something to contribute there. So, I don't know, but I don't want it to be forgotten how we get hospitals involved in that. CLIAC CHAIR: [CLIAC DFO], do you have a comment? CLIAC DFO: I do. Thanks, [CLIAC CHAIR]. I just wanted to respond to [CLIAC MEMBER] comment, which is a really good one, but maybe clarify a little bit. The tri-agency work group is intended to be exactly what it says it is, which is for three government agencies to discuss government decision making and government processes, especially around emergency diagnostics and the roles that our three agencies all must play for that to work somewhat smoothly. And in fact, there's no one on the tri-agency task force outside of those three agencies. Now, however, what we also have put in place in 2018-- and I think this is what [CLIAC MEMBER] is referring to, because I completely agree with her point-- is what's called a memorandum of understanding between CDC, APHL, CSTE, and ACLA around surge testing during an emergency. And she's absolutely right that following Zika, when we in public health-- particularly we at CDC-- realized we needed help from commercial labs to respond to Zika and we had no relationship with those labs, we took steps in 2018 to create those relationships with the large commercial laboratories in the country for the purposes of surge testing support during a public health emergency. And while that work was helpful and I'm glad we had some of those relationships in place 15 months ago, what's clear that we didn't anticipate and now we-- I feel foolish. We didn't anticipate that not only would we need commercial laboratories, but we'd need the entire clinical laboratory system to be supporting surge testing for a public health emergency. And looking back, that MOU really was-- I mean, it's not-- it wasn't as significant-- it wasn't treated as significantly important in 2018 as it now should be. And I think we need to expand the membership of that group of organizations that work together in advance of the next pandemic. Over. CLIAC CHAIR: So, our conversation has moved to rapid scale up of newly developed tests in the setting of a rapidly evolving pandemic. And we kind of touched around, is the tri-agency the way to go? We talked, yesterday about LDTs. We had a recommendation from yesterday that we didn't like, but I word smithed it overnight and was wondering if this is the time to think about it and have this conversation, because the tri-agency right now doesn't have that relationship. But yet, we heard from Dr. Villanueva there is a fledgling attempt with the National Laboratory Response Network. And Mike Pentella raised the comment, should clinical laboratories now become a layer of that NLRM to be able to provide that rapid search capability? So, in red is what I threw out and ready for your reaction. Do you want to discuss? Do you want to table? What do you want to do? [CLIAC MEMBER] wants to discuss. CLIAC MEMBER: I would like to discuss. But I also want to make a clarification from yesterday. I think that when some of us were talking about the Lab Response Network, we weren't-- at least I wasn't suggesting that they oversee the response. I mean, I think CDC and FDA and that part, you know, is working and is being iteratively improved. All I think that we were trying to say is that registry that could be given to FDA of these presort of registered clinical entities, laboratories, that would be available as a mailing list, as something that a website could pop up and you just go on and say, we're an LDT certified lab. We're launching as of such and such a date.

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And if there's follow up paperwork, fine. But it doesn't-- much like the discretion law, it doesn't have to hold people back. And then again, that leaves CMS and FDA and CDC to focus on the laboratories that are-- that don't maybe have previous testing experience. And that's really where I think the-- we don't want to stop anything moving forward. But yet, there's no way for any of the tri agencies to know who has this expertise and who doesn't other than your proficiency testing or your CAP inspections or whatever. I mean, I would almost argue that we're all doing LDTs anyway. I never propped up any EUAs that I didn't verify as an LDT because I know I will get inspected by CAP coming up and they will be looking at my verification. And so, you almost could grandfather those-- grandmother, grandfather, grand person, whatever-- into the fact that they are performing LDTs. They will continue to perform. And when the next inspection comes in, whether it's a self-inspection or a CAP inspection or a CMS inspection, the rubber will hit the road if they've done something wrong. They're already in that cycle of LDTs. So that's kind of what-- but the registry or the notification might be something that would align with the LRN. So, I mean, I like what [CLIAC CHAIR] said. I like what [CLIAC MEMBER] said. I think we can whittle this down to something that would be some kind of a recommendation, knowing that we eventually have to have laws changed and longer-term things happen. That's just my two cents. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I want to just quickly interject some of my thoughts behind my statement. Maybe I have the wrong agency when I mention the NLRN because I was thinking throughout this year, our local public health lab would reach out to all of the clinical labs in our community and say, hey, guys, we either have this new test or do you need these reagents? And so, from that, I was thinking, is it APHL or is it NLRN that is the distribution arm and the communication arm to the clinical laboratories in that jurisdiction? And is that the communication strategy? Because during this last year, our local lab, if we had the right instrumentation, personnel, whatever, they would be able to get us reagents, et cetera, that we could not access any other way. So, I know there is-- I know there's a network. I know maintaining a database will be a life unto itself. And how can we adapt it to what appears to be an existing network? I'm going to stop talking and Kathleen Perez has popped up. Oh, I'm sorry. My chat thing jumped. CLIAC MEMBER: OK. So, I wanted to just go back to yesterday and be very clear on what the purpose is of this motion. What I understood yesterday was that you're looking to identify these laboratories that would be able to create these lab tests and not be required to go to the FDA for approval? I need to be real clear if that's what you're still saying. CLIAC MEMBER: Yes, [CLIAC MEMBER], that was my intent that under the umbrella of either the NLRN or APHL, through their network, that this would be one of those outer concentric circles that would expand their authority to allow these-- another layer of laboratories to provide that test. CLIAC MEMBER: Is this happening anywhere for anything right now, where tests are created, and they do not have the oversight anywhere? [INTERPOSING VOICES] CLIAC MEMBER: The FDA is not involved. CLIAC CHAIR: That's a good point. I am not familiar with that. I do know-- my experience is they were able to make testing available to me-- new system, new platform, which I did not have. But that system was FDA approved. So-- CLIAC MEMBER: But it is CMS-- but it's CMS who oversees laboratory developed tests, just to be clear. So, this is going on with scientists that are-- the FDA doesn't approve a laboratory developed test, but CMS and CAP, their deemed agent will inspect a laboratory who is doing laboratory developed tests. And that is where the quality and the review comes into that process. So that has been an allowable process with CLIA since '88. CLIAC MEMBER: The FDA doesn't have to be involved at all? CLIAC MEMBER: You do have-- if you're reporting-- no. They're not involved. But they have worked together. If I perform a laboratory developed test in my laboratory, then I am responsible through CMS to use language that alerts my physician-- Carole, think of it sort of like an orphan drug. Sometimes these are tests that a company will never take to market because the revenue might not be there. So, there's a canned comment you put in for your inspection that this is not FDA approved so that there is a reference to the FDA. We have full transparency to allow providers and other people to know that this was verified in lab xyz. And that goes with every report. You cannot legally report an LDT without disclosing that. So that is part of the process for CLIA LDTs. CLIAC MEMBER: OK. Thank you. CLIAC CHAIR: The line-up is [CLIAC MEMBERS].

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CLIAC MEMBER: [CLIAC CHAIR], I'd like to ask-- pass to [FDA EX OFFICIO], because I think he might want to comment on [CLIAC MEMBER] comment. CLIAC CHAIR: [FDA EX OFFICIO]? FDA EX OFFICIO: Yeah. So the official position of the FDA still-- even though there was an HHS statement in August of 2020 that said the FDA cannot require COVID tests to be reviewed-- LDT tests to be reviewed-- and even after that, the FDA has remained an official position that the FDA does have regulatory authority over all test development in the US, including LDTs. That's an official position. I'm just stating that. However, for Carole's benefit, as I explained yesterday, for a long time, the FDA has not always actively regulated all LDTs. There are some that we still did. And there's a long history of trying to deal with this. And many stakeholders are involved. And it appears that Congress has taken up this. And as has been mentioned, there are two bills. And the FDA officially supports a legislation solution to really clarify this so that we can all be assured of who's responsible for what, and ultimately that we know that all testing in the United States at least meets some minimum bar. CLIAC CHAIR: Right. Thank you. [CLIAC MEMBER], did you want to make-- CLIAC MEMBER: Yes. Thank you. I'd like to add about the Laboratory Response Network. I reach out to all clinical labs throughout the state every week with a newsletter about COVID-19. And I try to educate them ahead of this, before this all occurred, that we are a laboratory system and that Laboratory Response Network is what builds that system. I'm an APHL member laboratory. But most importantly and foremost, it's my relationship with the LRN that makes me lead that effort for laboratories in Iowa. And I think that it's a very important role so that laboratories can be unified in their response and know what's going on at all levels. I like both of these comments. I think there is a possibility to synthesize them into one comment. Because I think as I'm looking at a separate layer of that clinical lab group, a group that would be involved and already precleared to do lab testing in a public health emergency is what's needed. We have those labs ready in most states throughout the country. And if they know their role is to do this, then that will build that strength to the system that I think [CLIAC DFO] is recognizing that's needed. I think that the public health laboratories can help the labs in their jurisdictions build that capability. Thanks. CLIAC CHAIR: Thank you. For those of you who are watching the changes made on the screen, Heather is transcribing from [CLIAC MEMBER] and [CLIAC MEMBER]. Next on the list [CLIAC MEMBER], did you want to talk about APHL? Or are you done with-- CLIAC MEMBER: I just wanted to say that it really wouldn't matter who-- LRN or APHL. But it would be-- since it is laboratory response-- I mean, I think in [CLIAC MEMBER] comment, he leaves it open to the tri-agencies and everyone to determine that. And that may be best. But you know, I still think that the Laboratory Response Network is more geared towards emergency. So maybe that's something to consider. But I don't think it has to be one or the other. As long as there's an existing registry, like [CLIAC MEMBER] says, we should use what's there. If APHL has one, fine. If LRN has one, fine. Just somebody needs to be able to have this ability for people-- for laboratories to offer up services and be registered I think is the bigger picture. CLIAC CHAIR: And [FDA EX OFFICIO], did you want to make any other comments, [FDA EX OFFCIO]? FDA EX OFFICIO: I'm sorry, no. Not at this time. My one comment was what I made earlier that [CLIAC MEMBER] allowed me to butt in. CLIAC CHAIR: OK. Thank you. FDA EX OFFICIO: Thanks, though. CLIAC MEMBER: Yeah. I've just kind of been thinking as we've been going through here and kind of trying to-- I don't know, kind of fill in the holes about how we might react quicker and better in future pandemics and those sorts of things. Kind of wanted to-- and again, being new, I'm not sure if this is the right place to bring this up. But just kind of wanted to put a more human face on that. I mean, it's important, I think, to make sure that we have access through the network for reagents and swabs and whatnot. But you need to remember, a lot of front-line workers died because they didn't have adequate PPE. They didn't have adequate testing up front. And so I just wanted to, again, kind of put that out there, that maybe as part of this Laboratory Response Network, that taking care of our personnel is an important part of what we should be thinking about as we think about how to do this better next time. And just-- and again, I'm not sure how that works out. But stockpiling and having adequate staff to take care of our people.

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CLIAC CHAIR: Yeah, I agree. Labs themselves ran out of PPE. You're right. [CLIAC MEMBER] has a comment. [CLIAC MEMBER], do you want to speak it? CLIAC MEMBER: Sure. And actually, I think Heather is typing it. And it's in a public health emergency-- I'm just trying to wordsmith this thing in all the input. When a public health emergency is declared requiring rapid expansion of new and/or existing clinical laboratory testing, the CMS, with the assistance of the NLRN, shall enlist the aid of CLIA-certified clinical laboratories with existing-- I like existing use of and/or proficiency in test methodologies readily adaptable to the new test to develop and use laboratory developed tests. These tests would have oversight by inspection agencies to include CLIA and CAP. And I think that summarizes a lot of input across several people. And as for the NLRN, there's nothing wrong with taking advantage of a network if it can help you. It doesn't have to be the NLRN, because as I understand, CMS under current practices has oversight over-- through CLIA and CAP of the LDTs. CLIAC CHAIR: Thank you. [CLIAC DFO] and then [CLIAC MEMBER]. CLIAC DFO: Thanks, [CLIAC MEMBER]. OK, so the LRN, although it's managed by the CDC, it's really designed to be a state-oriented network in terms of its engagement with clinical laboratories. And so, the CDC program that runs the LRN relies on state public health laboratories to do the outreach and engagement and build the networking, if you will, with the clinical labs in their jurisdiction. And I think in some states, that works extremely well. In other states, particularly those who have limited resources for public health, it doesn't work very well at all. And I guess I would ask the committee to consider whether this engagement with the clinical laboratory community in advance of the next emergency, which I think we all agree is critical, needs to be, frankly, a little more centralized at the federal level so that it can be a little more directed across the entire community and not be relatively variable from state to state. And I think that's part of the reason, if you-- I mentioned this yesterday and I think it's an important thing for CLIAC to understand. I think that's part of the reason why the LRN has not been responsible for the laboratory response to COVID. It was a federal response as opposed to a federated response. The LRN was originally created for unique terrorism incidents that would happen in a particular jurisdiction or locality. It's also a highly complicated system, in that they have their own way of-- accrediting is not the right language. But they establish expectations and requirements of all the public health labs that are part of the LRN. They all have-- they go through-- they have their own proficiency testing. They have their own-- they use the same assays for the same tests designed around the classic bioterrorism and chemical terrorism agents that would be used. So I guess I'm wondering whether the federal agencies should be given-- more emphasis or more expectation, I think, should be placed on the federal agencies to create this wider network of clinical labs that are capable of participating in public health responses. Over. CLIAC CHAIR: Thank you, [CLIAC DFO]. CLIAC MEMBER: Thank you. I think my comments were going to echo [CLIAC DFO] very, very much in the spirit that we saw incredible-- through this pandemic, incredible variation in responses in the states who had previously engaged with their local hospital systems and good relationships did better. I think there is quite a bit-- as [CLIAC DFO] said, quite a bit of variability in those relationships and that infrastructure-- official and unofficial relationships. And it seems like a very valuable suggestion, great suggestion for [CLIAC DFO] to get a more federated response would be appropriate. As we saw with the current pandemic, a decentralized response was not very effective in many ways. So, I think that's a wonderful suggestion. And I was going to suggest something similar to that effect. Thank you. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, to go along with what [CLIAC DFO] has just mentioned-- and previously, he made a point to clarify these agreements were made through the memorandum of understanding. So perhaps it would be good to insert this memorandum of understanding in our statement and make clear that this memorandum of understanding is with the federal government. This is not where we need to rely on a state by state approval of allowing these labs to participate. It would be-- in this understanding would be a direct agreement between the labs through this memorandum of understanding that there's a way to go ahead and insert that specifically into this recommendation. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. There's been chat around which agency-- or plural-- would be the central coordinating thing. And I want to come back to how detailed do we want to be in our recommendation? The devil will be in the details of how this plan rolls out. And do we want to restrict the creativity of the agencies by being too restrictive in our recommendation? I say that because that's how I worded my original wording, which is where the agency-- it's in yellow at the top-- shall enlist the aid of CLIA-certified clinical laboratories. Ignore the blue. The line is the green. With existing-- that means you're already doing it-- and proficient-- that means you've already demonstrated proficiency. And then I just made it very vague. In test methodologies, nucleic acid, antigen, antibody-- that's a broad-based term-- readily adaptable to the new test. And then after hearing this discussion, perhaps my final modification would be adaptable to the new test approved under-- I don't know-- the new test apprentices LDTs approved by EUA. Something like that to indicate there

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was an approval process at the primary lab that brought it up and now it's being expanded. And that-- I don't want to put it in the wording, but it would be whatever this program is that the delegation of that would go to the primary lab along with the reagents and the validation panels to show that as you expand it to this outer circle that the outer circle can perform the testing correctly. I did not want to put that level of detail in this recommendation. So that was my intent. And it is a very narrow pipeline-- very narrow, because I felt everything else, we talked about was too hard to get our arms around. So, I'm going to throw that back out for discussion. [CLIAC MEMBER], you have a comment. CLIAC MEMBER: Yes. I think having worked through the conversation, I agree that this should be federal and not federated. So, the NLRN could assist in the dissemination of information in as much as it can. But I'm not sure having that up front is necessarily an appropriate thing for a pandemic. And then the other question I would have to do is, I can understand why you left this open, except that I think the vague nature of the relationship led to some non-transparency in terms of who is to approve LDTs, FDA versus CLIA, and have oversight over them. And this held up LDTs for about a month or six weeks, been here almost two months. And I personally feel that the CDC was set up for oversight over pandemics. The CMS has been set up for oversight over laboratories. And the FDA has been set up for testing. So, by including the three, it would be-- and I like the idea that Monique has of an MOU that the process will be distributed across them in the most efficient way. Now, if the MOU can be designed in advance of a pandemic based on our experience with the last one, we would take the best of what we did and try to eliminate any areas where it became less efficient because of redundancy of oversight or non-transparency and oversight. But I would make a case for being able to use the names of these three agencies, because I think that they will still be there. And when the CDC is replaced by another agency, I think it will be very clear that. CLIAC CHAIR: [CLIAC MEMBER], your audio just faded out. CLIAC MEMBER: Oh, OK. Sorry. I think that if the CDC was replaced by another agency that it would become very clear that the CDC responsibilities would be taken by that agency or some other group of agencies. So, I don't see this as being so limited by mentioning the three agencies, but perhaps more in strengthening the idea of cooperation across the three agencies. And so, in retrospect, using the retrospect, as Dr. Fauci likes to say, we don't necessarily need to lay blame. But retrospectively looking at where did the inefficiencies come from? Did they come because there was a lack of understanding? Did they come because of a politicization of the pandemic? And how best would we eliminate that? Would it be by having an MOU in advance of a pandemic that states how it should be handled? And granted, that's based on just previous experience. But this could be modified as each new experience is learned. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I want to just interject in a second. In this sentence I have where it says the Laboratory Response Network, I would like to replace those four words with CDC comma CMS and FDA. And then we can work with that because I had misattributed this. I also want to go back to my original wording-- CLIA-certified clinical laboratories with existing and proficient in-- I do not like and/or, because then you get. CLIAC MEMBER: The only thing that bothers me from a grammar point of view is existing is an adjective and proficient is a noun. CLIAC CHAIR: So, it could be with existing and demonstrated proficiency. CLIAC MEMBER: Yes. CLIAC CHAIR: And then I'm going to get off my soapbox. And it looks like [CLIAC MEMBER] has made comments and then [CLIAC MEMBER]. CLIAC MEMBER: OK. So, I would like to go back to kind of what I thought where this whole issue came from. And I think it was the Washington laboratory, if I remember correctly. And basically, the laboratories asked why, if I can produce an LDP doing a non-emergency, why do I have to go to the FDA to have my LDT approved during an emergency when I have got all these problems I'm trying to deal with? And so, I would like to direct the question to [FDA EX OFFICIO], who I can sidestep it as you wish. But does-- my question is, does the FDA already have regulatory discretion to not require a EUA in laboratories that its determinants do not require it for performance of an LDT during a declared emergency? FDA EX OFFICIO: So, I'll just-- I can respond with what the official FDA position is again. The FDA continues to exert-- continues to express that they see themselves as having authority over all test development, that during a declared emergency that it's critical to have accurate testing and that it's especially critical-- false positives as well as false negatives can have potentially devastating consequence. So, the risk level in an emergency is such that the agency believes-- the FDA agency believes that it's important that they have oversight of test development, especially in a pandemic situation. I'm just stating the official position of the FDA.

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CLIAC MEMBER: Can I modify or expand one more time-- sorry, [CLIAC CHAIR] -- to say, is there a distinction between the in-house performance of that LDT versus the manufacture and sale of that LDT? And would that make the FDA any more so-called confident that a laboratory who created the LDT could perform it without obtaining a EUA? FDA EX OFFICIO: So, the FDA position here is long standing. And the more newer positioning is that this plus all other LDT and all other test development is best addressed through new legislation. And there are two bills-- you know, it's the FDA's position that that's a perfect opportunity for Congress to lead here and create clarity and ensure access, innovation, as well as proper oversight. That's the best I can offer. CLIAC MEMBER: Yeah, I get that. And so that's why I wanted to make my last comment. Then I will stop. And that is whether or not this recommendation can really go anywhere without addressing the issues that [FDA EX OFFICIO] just brought up. I don't know what a Secretary is going to do with the exception of saying it's out of our scope. This has to go to Congress. Thank you. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. So, what I'm hearing-- there are two issues that are mixed up in this discussion. The draft language I put out was really a very narrow focus. And LDT already distributed to a central lab that can then enlist other labs with the same technology to implement under a very tight constraint. What I'm hearing is the issue brought forward by Jim Crawford, Alex Greninger our last meeting, and then Matt Binnicker and Dara Eisner in this meeting. And it's the gap, exactly as you've identified, [CLIAC MEMBER]. It's a related but a slightly different issue. And it's an independent laboratory-- thankfully, a high-quality laboratory-- that is manufacturing and then performing the tests from scratch. And when we talked about the spectrum of those type of laboratories, I've heard discomfort from members of the panel stating that some level of oversight would be desirable, because we've encountered the flip side of pop-up type laboratories that were performing their own manufacturing tests without adequate quality. I think if we wanted to pursue that, [CLIAC MEMBER], we should have a separate recommendation coming out of here. And then I would see that directed at the FDA, unless I'm wrong, because it would be an EUA type of request or recommendation. Now there's silence. And I want to say a time check. We have 10 minutes before this session is scheduled to end. And do we want to table the remainder of this conversation to the end of the meeting? Or do we want to try to at least get one recommendation out? The recommendation on the table is in red. But as [CLIAC MEMBER] has pointed out, it may be useless. And that's fine. CLIAC MEMBER: Well, this is [CLIAC MEMBER]. I think I'm next up. I'm a little bit unclear why-- which one of the recommendations we're looking at and how we might be able to merge them, because I think [CLIAC MEMBER] makes a really good point down in this recommendation that I think touches on what we're talking about, that-- and maybe it's not CDC and CMS, that it's FDA. It's all three of them develop the criteria-- whoops. I'm sorry. OK, there we go. Develop criteria by which labs can qualify. And so, he's stating that we actually need to develop that criteria that we've been discussing, and then also the system and the registry. So, is this recommendation additive to the one you've got on there, [CLIAC CHAIR]? Are-- OK. And then there's [CLIAC MEMBER] down there, as well. So, are we trying to come up with one recommendation, or are these going to be iterative recommendations from the three of you? CLIAC CHAIR: From my perspective, [CLIAC MEMBERS] were riffing off of my original recommendation. So, if we were to send something forward, assuming it would be useful, we would find a synthesis of the three comments. I want to comment there are folks who've jumped on who want to make comments. And I would like to let them. So, it's [FDA EX OFFICO] then [CLIAC MEMBERS]. FDA EX OFFICIO: Yeah, just food for thought is that based on the current pandemic and the lessons that the FDA has learned, the EUA legislation allows us great flexibility in applying our oversight to EUA tests. And as long as that flexibility remains unchanged, it doesn't need to change, perhaps. It's the intention of the FDA to apply all the lessons to the next time. We hope as a nation-- not just federal government, but all stakeholders come together, and we do an incredible job of learning all the lessons and applying the lessons to how we prepare our country for the next time it happens. It's not a matter of if, but when. But the FDA will take all the lessons learned and will directly apply them at the beginning of the next pandemic. That's our intention. The EUA legislation, the law, existing law, gives us that flexibility. And there's no reason why we wouldn't apply it, especially in the very beginning when we all desire to see as much quality testing remain available as possible. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, this may be where the preacher stops preaching and starts meddling. But I did want to ask a question, because having looked through an awful lot of package inserts trying to figure out what kind of platforms and all we wanted in the lab, I came across a lot of these tests that had EUA but had, I think, from a quality standpoint, really crappy underlying research. In other words, for their positives, they would spike a sample with COVID-19. And then guess what? 99.5% of the samples were positive. And with no clinical data whatsoever. And sometimes those numbers were 10,

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15, 20 patients. And so, I don't know if this is, again, if this is an FDA purview or purview of what we're trying to bring forward. But you know, I think before somebody gets an EUA, I would love to see them have a little bit more clinical data and a little more clinically relevant data before they go putting that out on the marketplace. As we've learned, a lot of those tests had to be kind of recalled or taken off the market. So that would be another thing I would want to see try to be rectified before we do this again. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. And thank you, [FDA EX OFFICIO]. The EUA legislation already in place, I think what we're hearing is a need for validation panels. I think that's what [CLIAC MEMBER] is saying, that in this rush to go along with the development, how do we validate? OK, next-- FDA EX OFFICIO: Yeah, if I could make a comment on that-- that's clearly in some of the published recommendations that Jeff and I have made about samples. One of the challenges is that everybody wants to develop their own test. And if the samples are very few, it's really hard to validate in a harmonized way. It would be much better, like the APHL labs, who, if I understand correctly-- and those who know better can correct me-- but most if not all of the APHL labs have a common set of equipment. And it's designed so that the CDC or any other developer can develop an assay that will work in all those labs. All they need to do is get the-- receive the kit, verify its performance, and they can get going. If we had a network of not just the local and state public health labs, but also a larger network of labs that have agreed to use common platforms and technologies, this would aid in immediate response to a new pathogen. It may not serve long term, in depending on how long the pandemic lasts. And obviously, more automated proprietary high throughput systems can come to play later. Just my two cents. CLIAC CHAIR: Thank you, [FDA EX OFFICIO]. Final comment for the session will be [CLIAC MEMBER]. CLIAC MEMBER: Well, that's a heavy responsibility. I was just looking at the wording regarding enlisting laboratories. And I find that-- if I was a laboratory in private practice-- a little concerning. Does that mean commandeer, draft, volunteer, exactly what does that mean? I think it gets back to [CLIAC MEMBER], and I think more recently [FDA EX OFFICIO], comments about having methods that are perhaps preordained, preregistered laboratory participants, and designed in a way that would be more standardized and easier to implement. And maybe there's a role for accrediting organizations to help recruit labs to this in the sense you want to become more of a voluntary approach. But I'm not sure which is best. But I think that word is just-- I find just a little bit uncertain and slightly troubling. Thanks. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I used that word and I didn't appreciate the connotations that would come with it. So that's my fault. As [CLIAC MEMBER] -- to quote [CLIAC MEMBER] from yesterday, the bread is still not baked on this one. And I would like us to take our break but still think about this during the hour. Also want to throw in another variable. [FDA EX OFFICIO] mentioned the approach South Korea took, which was to authorize a limited number of tests and pre-certified laboratories. Now, [CLIAC MEMBER] keeps popping up how that will affect restraint of trade and issues like that. But is that something we want to talk about? So, leaving you with those thoughts, we will continue that this afternoon. And then I have a favor for the CLIAC members. I would like to take a picture of you. And I would like a picture of you looking into the camera. And it would be great if you want to smile. But you don't have to, so that instead of all the distracted pictures I've done of you. And let's see. Let's see. Are you all close enough? OK, so I'm going to tell you to blink first. Close your eyes and blink. And then I'm going to count to three. And when I yell three, I'm snapping the shutter. OK, so is everybody ready? You can decide if you want to smile and show your teeth or not. OK. 1, 2, 3. OK. Gotcha. So, this session is adjourned. And we will reconvene at 2 o'clock Eastern time. That is 11:00 AM California time and figure out your time zone in between. If everyone would please turn off your video and mute yourselves during the break, I'd appreciate it. See you in an hour. Thank you.

Expansion of Point-of-Care Testing, Self-Collection, and Self-Testing CLIAC CHAIR: Welcome back, everyone. It is noon-- I'm sorry, 3 o'clock. Waiting for a few more cameras to go on. The final session today is on expansion of point-of-care testing, self-collection, and self-testing. The first presentation will be from Ms. Nancy Anderson, who will provide an overview of the expansion of point-of-care testing during the COVID-19 pandemic. The second presentation will be from Dr. Tom Stenzel, who will present an FDA overview on the topic. These are online presentations 14 and 15. If you wish to provide a five-minute public comment, please email cliac@cdc.gov if you are not already on the agenda. We do have one public comment scheduled. It's from Dr. Christina-- I'm going to mutilate her name-- Wojewoda from the College of American Pathologists. Once the presentations are done, it will be followed by a committee discussion and then, following that, a quick discussion around future CLIAC topic proposals. With that, let us begin. And Ms. Anderson, we will start with you. Nancy, go for it.

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The Expansion of Point-of-Care Testing During the COVID-19 Pandemic Nancy Anderson, MMSc, MT(ASCP) MS. NANCY ANDERSON: Thank you. And good afternoon, everyone, back for your last important discussion of this meeting. The purpose for my presentation is really just to give you some background and set the stage for the questions that we will be asking you to consider, although this topic has come up in earlier presentations this morning and yesterday, as well as in some of the comments that various people have made during the discussion. So, it's not a topic that will come as a surprise to anybody. And although the title of this presentation is the Expansion of Point-of-Care Testing, the questions that we will be asking you also have to do with the fact that there have been a number of self-collection devices and self-testing devices, or sometimes at-home collection or at-home testing devices that FDA has authorized as part of the response. So, because those devices and tests are not, in most cases, subject to CLIA, I don't really have as much background to share on that. But I will give you a little bit of data that reinforces what Monique already shared yesterday about the growth of certificates of waivedr. I'll also talk a little bit about past CLIAC discussions related to waived testing. This is not a new topic, although there are some different aspects that have come out in the pandemic response. But it's been a concern. Ensuring quality in waived testing sites has really been an issue of concern to CLIAC since CLIAC's very first meeting. So I'll give you a little bit of history on that, and then some information about what the government has done to help ensure the quality of testing in these sites, and end up by asking for your input on what else could be done or where are there gaps. So, with that, let's go ahead to the next slide. This is a bar chart that we maintain and have updated as the years go by that showed the distribution of the different types of CLIA certificates. The dark blue bars on the bottom that are the largest percentage of laboratories are the labs with certificates of waivedr. The green bars in the middle are the provider perform microscopy procedure certificates. And the top turquoise bars are a combination of certificate of accreditation and certificate of compliance laboratories. So, looking at the chart overall, you can see that since about 2000, there has been a pretty gradual but steady increase in the number of certificate of waivedr labs. The other certificates have remained relatively the same, although starting in about 2017, there was a bit of a slight decrease in the PPM, Provider Performed Microscopy certificates, as well as the certificates of accreditation and compliance. But the biggest difference in looking at the chart as a whole came about since 2019 where you see the jump there in the numbers of certificate of waivedr laboratories. And that increase represents the more than 38,000 certificate of waivedrs that have been issued in the time since the pandemic began. So, if we can go to the next slide, Let's look a little bit more at what that jump in the blue bar represents. This slide takes those 38,000 labs and breaks them down into their laboratory types. When labs apply for a CLIA certificate, they self-select a laboratory type. So, we have combined some lab types and separated out into bars that show what the distribution is across the different types of 38,000 labs. The largest number, as you see there, are the physician office labs, followed by pharmacies. And then we come down to assisted living facilities, home health, and intermediate care facilities, and then a group that is known as other. Because labs do self-select, we really do not know. There's probably some overlap between some of these categories. There are not standard definitions. And so, I can't say what other represents. But another category, which is really one of the smaller bars on this chart that we know has been involved in doing a number of the SARS-CoV-2 testing, are the skilled nursing facilities, which are way over towards the other end of this chart. So, I think that is it. The hospital and independent labs are grouped in somewhere in the middle of the chart there. Public health labs and community clinics are over, again towards the left, a little bit closer after others. So, let's move to the next slide. And now we pulled out just a little bit of interest to look at where these peaks in the growth of certificate of waivedr occurred. For the physician office labs, you see there's been-- pretty much there have been new certificates going back to January of 2020, and with a peak in December. But there has not been a single month where there have been fewer than 500 certificates issued for POLs. Let's go to the next slide. We just pulled similar graphs for some of the other laboratory types where there have been increases in waived testing that we know of. And first of all, I just want to make note of the fact that the number of labs represented in each of these, the scale is not the same. So, where you see assisted living, it goes from 0 to 1,400. But if you look at the skilled nursing graph, it goes from 0 to 160. So, it's not the same scale. But the peaks are able to be seen on each one of them. Pharmacies were the first lab types to show peak back in June of 2020, and then have had another peak in December of '20, and again in March of '21. Assisted living and skilled nursing facilities had their biggest peaks in September and October. And then schools and student health services peaked in November and December of this past year. So that is just some additional interesting information about when these certificates have been issued. And with that, we can move on. So with this big growth in point-of-care sites and certificates of waivedr that have been issued, one note that I meant to make up front but did not is the fact that FDA's EUAs for point-of-care testing is being considered the same as waived testing. So whereas previously tests have gone through the specified FDA process for review of waivedr, in the case of the COVID testing, tests that have been granted an EUA for use that point of care has meant the same thing as being considered waived under the terms of the emergency. So clear requirements for waived testing are minimal. And this is

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the point that I think several people have raised in earlier conversations-- the fact that we want to ensure quality in these testing sites. However, the requirements under CLIA say that these testing sites-- the only requirements are that they enroll in the CLIA program, pay their fee, and get their certificate of waivedr. Beyond that, the only requirement is to follow the manufacturer's instructions for testing. And no changes can be made to those instructions, or the test complexity defaults to high complexity. So, the testing sites, the labs, the other testing sites have to follow the manufacturer's instructions. However, there are no personnel requirements in sites with a certificate of waivedr. None of the other CLIA quality standards apply to waived testing. Certificate of waivedr sites are also not routinely inspected, unless there is a complaint, or unless these sites are performing testing that goes beyond their certificate type. So, examples on the right illustrates a situation that happened during the pandemic where antigen tests were first rolled out in nursing homes in Nevada. And there were concerns that were raised about the high numbers of false positive results that were seen in those sites. And those could have been due to user error when performing the waived testing. So, at the time, the testing was stopped in those facilities. And one of the lessons that I think CDC and others learned from this was really the need for more guidance, more support to help laboratories and testing sites properly perform testing in these sites that really were not subject to a high degree of CLIA oversight. So next slide, please. So, this is what I mentioned, that we thought it may be helpful, because discussions and concerns about waived testing do go back to the very first CLIAC meeting, which we have a picture of on this slide. And this is not a new issue. But CLIAC has, on multiple occasions, looked at issues related to ensuring quality in waived testing, looking at the criteria that should be used for approving tests for waivedr, looked at data that are available to support the requirements for waived testing. And so over time, since this first meeting, there have been 20 different recommendations. Five of these recommendations have been expressing concerns or suggesting good laboratory practices to follow. There have been three recommendations that have addressed the need to collect waived testing data and information, and then one recommendation-- which was made the most recent discussion, which was in 2014-- supporting opening up the CLIA law to allow changes to waived testing requirements, because these minimal requirements for conducting waived testing are requirements that are in the law. So, it is challenging to think about what more can be done without going back to changing the CLIA law related to waived testing. I also mentioned that some of the recommendations made by CLIAC related to the criteria used to approve test for waived status. Or, if you go back to those very earliest meetings, CLIAC actually weighed in on waivedr decisions for a few test systems in the very first years that CLIA was effective. So next slide. So, what have come from all of these previous CLIAC recommendations related to waived testing? One of the outcomes is highlighted on this slide. In 2005, CLIAC recommendations to ensure accurate and reliable waived testing were incorporated into a CDC MMWR Recommendations and Reports publication. Following that, in a subsequent CLIAC discussion, they said, you know what, a lot of these point-of-care waived testing sites are probably not going to read CDC MMWRs. So, we need products that are user friendly, written in plain language, can be posted in waived testing sites. And that led CDC then to subsequently develop the several booklets, which you see highlighted here, as well as a poster and an online training to encourage good laboratory practices for performing waived testing. These products have all been very well received. We have made the booklets available in English and Spanish. And we continue to distribute. They're all available on our CDC website. And we continue to distribute them freely in the mail, or if we can participate in exhibits, professional conferences, and other meetings. Since the pandemic began, we distributed almost 3,000 booklets requested through the website. And one of the things that I think is notable about this is that those have strictly been requests that come to us for these materials. We have not been able to go to any meetings, or conferences, or really do any promotion in the last year. And yet, people have still been requesting them. The other screen that's highlighted in the background on this slide is the online training, which corresponds to the Ready? Set? Test! booklet. And since January of 2020, more than 6,000 individuals have taken the online training, or have registered for it, with about 4,800 completions. And looking at the rate at which people were taking this training before then, that's about twice the-- double the rate that it was previously. So, there has been uptake of these resources. OK, now we can go to the next slide. The other thing that not only CDC but CMS and FDA have also done so far to help ensure the quality of the testing that is going on in these waived and point-of-care sites has to do with the different guidance that has been developed and has been posted on all three sites. In addition to FAQs that have been posted, these pertain to performing the tests, as well as how to get your CLIA certificate. And Monique talked about that in her update yesterday morning. So, these are the resources that we have developed. Now CDC has also-- on the topic of the self-collection and self-testing, CDC has also developed a web page specific to self or at-home collection and testing. And all of this information on all three agency's websites are available either on their coronavirus sites or on the CLIA websites for each agency. I think that is it for this slide. So, we can go to the next slide, which is the last one, which leads to the questions that we would like to have you consider and give us input on today. The first one-- I'll go through and just read them. Given the rapid expansion of the point-of-care testing, self-collection, and self-testing, we would like to hear from CLIAC, where do you see gaps in guidance or information that is needed to ensure the accurate and reliable SARS-CoV-2 testing? And how can the three agencies that are part of this committee help fill

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these gaps? We want to know, for the materials that are available now, how well are they reaching the nontraditional facilities or sites performing the SARS-- ooh, just noticed a typo there-- SARS-CoV-2 point-of-care testing? How can we increase awareness and better promote the use of these existing materials and the guidance that we have already written? And then, last, a question focuses specifically on the self-testing and related self-collection that are not covered by CLIA. Should HHS do anything to ensure accurate and reliable testing in these settings? So that ends my introduction. And with that, I am going to turn it over to Dr. Stenzel for his presentation before we move to your discussion. Thank you. DR. TIMOTHY STENZEL: All right. Yeah, thank you. You can move to the next slide, please. So, all of this discussion is going to be about increasing access to COVID-19 testing. That access takes the form of-- in many forms. One is we're very interested in low-cost testing, rapid testing, widely distributed testing, of course accurate testing. But one thing with some of the rapid tests, whether they're in point of care, or actually in the home, or the other nontraditional sort of sites that may have new CLIA waived certificates, these tests can be produced-- especially the rapid lateral flow test-- in extremely high volumes compared to other kinds of tests. And so, we we'll touch on today point of care, home collection. And that's where individually patients, by prescription, or now direct-to-consumer, can get a collection kit at home, collect the sample, put it in the mail, get a result in a couple of days. And then at-home testing, where everything is done completely at home. Next slide. So, a couple of milestones-- oops, back one slide. So, in March of 2020, we authorized the first molecular point-of-care test. So that happened pretty quickly, obviously. And then, not July, but actually in May-- that's a typo, May of 2020-- we authorized the first rapid antigen point-of-care test, and in September 2020, the first serology point of care. And then, finally, just last month, we authorized the first in a series now of tests that can do serial screening. And I talked about that in my last talk. Just to go over some of the numbers here, as far as home testing, over-the-counter testing, and direct-to-consumer testing, we have authorized a total of nine different submissions for at-home tests. Six of those are over-the-counter, meaning they do not require a prescription. And then, when it comes to home collection, we have authorized about 59 home collections-- I mean, rather, 53 home collections. 12 of those are direct-to-consumer, or otherwise don't require a prescription. So, a total of 18 home collection and our home tests can be requested by consumers, patients themselves, without need for medical authorization. And then they can find out what their status is. We do, in all cases, encourage-- even though it might be direct-to-consumer, or over-the-counter-- that patients alert their health care professionals, their clinicians as to the results especially, obviously, if it's positive. One of the issues that may come up-- and I won't really touch on it-- is, in some cases, there are reporting mechanisms built into these assays. We have not required home tests to have a reporting mechanism at the time of authorization. However, all have agreed to work on that as a post-market commitment. Some came with it ready made. And very recently, I know that the systems have been put in place that these home tests that are connected have begun to issue results that public health authorities can view. And this is a tremendous advance, obviously, to track disease rate from the home. And this is just the beginning of this kind of testing. Of course, we're using COVID here as an example, because this area has really exploded as far as creativity of test developers, and submission to the FDA, and authorization. So next slide, please. We still want these devices to be as safe as possible, given EUA relaxed expectation, and accurate as possible. We said very early on that point-of-care tests, especially the rapid lateral flow, should have at least a positive percent agreement or sensitivity of 80%. We've seen some come in much higher than that. And unfortunately, we've denied authorization to those that came in and had sensitivities less than that. We did make it widely known, beginning with a piece in The Hill that Jeff Shuren and I wrote back in September of 2020, that we're open to serial testing to bring performance up. And the concept here is that two or more tests are done within a defined time period and may increase the sensitivity. I think that is absolutely what can happen. However, as I said earlier, we have not received a single submission for serial testing that we could authorize based on data. Our new policy allowed it based on performance and symptomatic patients and required post-market studies. So, we will be collecting that data as soon as possible. Next slide, please. So, for point-of-care testing, we want those instructions to be simple and clear, to be able to be followed by folks who are not trained laboratorians. And as we saw in the prior presentation, there's a whole lot more certificate of waiver sites that are new to this kind of testing. So, it was important that, even though these are easily authorized tests, that they're simple enough, the instructions are clear enough, that they can be relied upon even with novice users. And that's largely borne out by our experience and monitoring this testing. There are some challenges that we saw. And maybe we can have a discussion about that. But some of the ways that we ensure that these methods are accurate and reliable in the point of care are choosing the right comparator method. We've used molecular assays, essentially high-sensitivity molecular assays that have an extraction method, as the appropriate comparator. And we also look at, what are the variables that can impact performance in the point of care? These variables also apply on tests as well. And that is things like humidity. So, a rapid flow test that requires liquid flow on an extracellular strip can be affected by humidity. Are the time period used in the testing-- if they're not adhered to strictly. What are the guard bands around, say, a reading time that would still allow an accurate test? We've clearly not authorized some tests that had non-robust tests when they were examined in these

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flex studies. And we asked them to go back and do some more work, and come back, if they can. There are certain times when volumes are used. And although we want that to be simple, obviously in a point-of-care setting, in a home setting, those volume can be quite variable in delivery. And we just want-- it has to be robust so that volume changes can be absorbed by the testing, both sample volume and any buffer volumes. And then, of course, as with most of the EUA tests, we have provided EUA templates with recommendations for all types of point-of-care testing. And those have evolved as technologies are advanced and additional questions of concern come up. And many times, to ease further the recommendations for testing-- one of those areas is in the symptomatic testing. For single-use asymptomatic testing, we now only require, pre-market, 10 positive asymptomatic patients for authorization pre-market. And still, we had a paucity of developers who did that testing and submitted the data to the FDA. And so that's the more recent serial testing and guidance to really kick start more screening with authorized point-of-care and home tests for screening purposes and testing asymptomatic individuals. Next slide, please. So, moving into home testing, I will address some of these. But it does greatly expand access. There are clear advantages to this. One is at-home testing provides nearly immediate results, just like in the point-of-care. There is a reduced risk of transmission. So, patients who are symptomatic, or even asymptomatic, don't have to travel to a health care site and have a sample taken. And both travel, and encountering the health care system, and perhaps having the sample taken by a health care professional-- that does present a risk for health care professionals and anyone else in the environment. So thereby, reducing that risk of transmission, it does increase preservation of personal protective equipment and supplies that health care professionals need in order to do this sort of testing. So, all in all, there are clear advantages for at-home testing and home collection. Next slide. There are different risks that we look at for home collection and home-test situations. Obviously, we're not even dealing with a health care professional in the home environment. Some developers have chosen to use telemedicine to administer this kind of testing. And while that is safety mitigation, it obviously can reduce access, increase cost as well. So, it's certainly not something that the FDA has recommended. But developers come in with whatever method they want to use for whatever purposes they have. And it's not for us, the FDA, to stipulate what and how tests should be developed. It's in the purview of each developer. In home testing or home collection, we have a new risk. And that is we're dealing with the public. And in the home environment, there are kids. And they may get access to the transport media products and/or the home test. And so, early on, we began looking at the safety of kits in a way that we never looked at before, because we haven't authorized for a large part these kind of tests ever before. And it was highlighted a couple of months ago when we got an urgent call from a family physician taking care of a family that had a home prescription test, or home prescription collection and device. And a young child got ahold of it and swallowed the component. And so we, of course, redoubled our efforts, did another top-to-bottom review of safety in the home environment. And additional labeling requirements have come out of that. And then, for a home-collection situation, obviously that sample is sent through the mail. And we consider safety issues and stability issues like, if it's during the winter, can it handle the freeze/thaw? And if it's during the summer, can it stand standing out on the tarmac in Dallas/Fort Worth airport for a number of hours when it's over 100 degrees? So, we ask for stability testing. Also, the actual tests that show up in homes and the collection devices will have a shelf stability. They'll have expiration dating. So, we do that for all the EUA authorized tests. We do ask for that expiration dating. That was highlighted recently for rapid test, the Abbott test. And we worked with our federal partners and with Abbott to extend dating even when kits were, as printed, were expiring. Next slide, please. And we have specific recommendations for validation of home, which is very similar to what I described for point-of-care in many ways. We do look at human usability a little bit differently. We want to make sure that home users, especially those where physicians and clinicians are not involved, understand the results-- not just understand how to do the tests, how to read the tests. But then, what does the test result mean? And so that additional study recommendations are included there. Next slide, please. And similarly, to the point-of-care testing, a lot of these are overlapping with what I've said before-- the flex study, the human usability study. So, they cover the entire workflow through test reading, through interpretation of that test, especially when, as I said, over-the-counter for home tests. I think that may be my last slide. And thank you very much.

Public Comments CLIAC CHAIR: Thank you very much, Tim. Right on time. Now we have public comment from-- and I Googled the pronunciation, let's see if I get this right-- Dr. Christine Wojewoda from the College of American Pathologists. DR. CHRISTINA WOJEWODA: That's the Polish way of saying it. Good work. Yes, I am Christy Wojewoda. I'm a pathologist and the director of the Clinical Microbiology Laboratory at the University of Vermont Medical Center. And I'm here today representing the College of American Pathologists. And we'd like to talk about the topic of expansion of point-of-care testing, self-collection, and self-testing in the age of COVID-19. Thank you for this opportunity to speak today. And we appreciate the work that's been done during this public health crisis. As the world's largest organization of board-

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certified pathologists and leading provider of laboratory accreditation and proficiency-testing programs, the CAP serves patients, pathologists, and the public by fostering and advocating for excellence in the practice of pathology and laboratory medicine worldwide. No test is so simple and straightforward to perform that erroneous results cannot occur, or an incorrect result is risk-free or inconsequential with regards to potential harm. However, point-of-care testing, self-collection, and at-home tests are important tools for helping slow the virus over the next few months until most Americans can get the vaccine. Among these rapid tests, each plays a role in helping frontline workers diagnose COVID-19, from point-of-care tests used in urgent care clinics and doctors’ offices, to at-home testing used in telehealth services. Detection in a variety of settings is needed since spillover infections in the local community or across state borders can cause clusters or outbreaks of COVID-19 occurring. These tests can help detect infections in these settings that may go unnoticed for some time, posing a risk to the individuals in the setting, particularly those who are more vulnerable to SARS-CoV-2, and to the wider community. Early identification of clusters, isolation of cases, and notification of contacts can prevent further spread within these settings and to the wider community. Clear requirements for point-of-care testing are clearly established. But at-home testing has caused some confusion, because there are some tests that are approved for at-home collection, but the sample itself is sent to a central laboratory facility for actual testing. And some tests are now authorized for at-home collection and testing. And these tests include antigen tests and nucleic acid amplification tests. To further complicate matters, at the Centers for Medicare & Medicaid Services has released guidance providing a temporary waivedr for some of these tests, exempting them from certain aspects of CLIA. For example, SARS-CoV-2 surveillance testing can be performed in a facility that is not CLIA certified, provided that patient-specific results are not reported. However, if patient-specific results are reported, CLIA certification and compliance is required. Given the settings that require COVID-19 testing, confusion abounds as to the appropriate testing, as well as regulatory requirements associated with testing for certain settings. CLIA should be required for point-of-care testing regardless of the settings. At-home specimen collection and at-home tests should have clear labeling prohibiting their use in settings outside of the home. Since many of these results will not be in the patient's medical records, we support wider and earlier SARS-CoV-2 testing of clusters to isolate cases and notify contacts to prevent further spread within these various settings and to the wider community. But more guidance is needed that is tailored for non-laboratory and communities defining each type and use of these tests, explaining the differences, and the regulatory implications associated with them. Thank you for the opportunity to speak today. And the CAP looks forward to working with CLIA, federal officials, and the clinical laboratory community to develop solutions for COVID019 and any future pandemics, although I hope that's not anytime soon. Thanks.

Committee Discussions CLIAC CHAIR: Thank you very much, Dr. Wojewoda. OK, that concludes our presentations. We are now opening for committee discussion. And I want to comment, it is 3:44 East Coast time. And we have until 5:30, at which time we will discuss topics for future CLIAC meetings. [CLIAC MEMBER] is first in line. CLIAC MEMBER: I'm going to pass for right now. Come back to me. CLIAC CHAIR: [CLIAC MEMBER] going to pass. And no one else has lined up. Come on, what's with you guys? CLIAC MEMBER: OK, I'll go ahead. CLIAC CHAIR: OK. CLIAC MEMBER: So, this question is to [FDA EX OFFICIO]. We've talked about this before. We see this happening today. You're still waiting for someone to submit very low-cost rapid testing that will help health care workers determine if they are carriers of COVID at home, to help the very low-income and at the poverty line who don't have $30 to go get a rapid test, who don't have a smartphone, and who don't have a network to find out if their test is positive or negative, to help those health care workers that are coming to help people that have now decided to not go into assisted care living and be treated and cared for at home. We understand this is urgent. It still is urgent. What will it take to finally have a public health offering from our country that will meet these requirements? We've waited long enough. We had a chance to come out with something early on. And we have nothing now. So what will it take to get this moving so that we put this

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together, our nation. If there's no vendor that wants to do this, this needs to be a public health offering. What do you need from us, on this committee, to make this kind of recommendation so we can test people en masse, and that we can empower the people to become a part of the solution, to isolate themselves at home immediately when they see that they have a positive test? We need this now more than ever, especially when so many people are not vaccinated yet. FDA EX OFFICIO: OK, so a bit of good news is that recent authorizations of the BinaxNOW for home, over-the-counter, and the QuickVue SARS over the counter-- both are very simple, inexpensive tests, around the $5 mark. When they'll actually be sold through various outlets, like drugstores and large chains. I don't know. But these are relatively inexpensive tests. And the US government is very familiar with the BinaxNOW and has purchased tens of millions of these tests, made them available to nursing homes, and in other settings. QuickVue is actually the QuickVue home test, which again is a very simple, inexpensive test. It's different from Quidel's earlier test that required an instrument. This QuickVue home test is the test being used in the NIH-sponsored study for home use in North Carolina and Tennessee. And that study has started, and hopefully will be wrapped up within a month. And we'll know the benefit of providing this. Both of these developers have received US government funds, not so much for the development as far as I know, but for the production of high volumes. And both of these developers can produce tests per month in the range of 50 to 100 million tests a month. And so, it is a tremendous boost. As a gesture-- and I have laid out in various pieces-- we believe, early on in a pandemic, the US government should not just fund efforts to expand central lab testing, but also should fund the development of point-of-care tests. We're very strongly supportive of the RADx program. Quidel is part of the RADx program. I'm not sure if Binax is, formally, but it received other US government funding. And the lion's share of the test in the point-of-care and home use that RADx is developing has not yet been submitted to the FDA. They're still in development. And one of the challenges with rapid tests of any sort, in order to make it super simple yet accurate, it takes a lot of work. However, once the US government has funded numerous companies to come up with technologies that can be used point-of-care and at home, those technologies can be adapted to the next pathogen that comes along relatively easily. And we'll obviously have a track record with those developers, so we know which ones are producing high-quality product, and in volume. And US government efforts are not just for the development of some of these technologies, but also the increased production of these technologies. I would say that we would have benefited very early in the pandemic with significant funding for all test developers of import, and that we're trying to catch up. Obviously, funding is not determined by the FDA. We can just-- our role is to recommend, and then receive, and review and authorize. So hopefully, that's helpful. Hopefully, that's a bit of good news. We hope there's more good news in the future. But thankfully, now some cheap tests but accurate tests are available on the market. I hate to say cheap-- inexpensive tests, but accurate. CLIAC MEMBER: That's what's we need. Yeah. Real quick question on the QuickVue and the BinaxNow. Those are both direct-to-consumer. Is that right? FDA EX OFFICIO: We use the term over-the-counter for in-home tests. They don't require a prescription. And we use direct-to-consumer when it's a collection device direct to the consumer. CLIAC MEMBER: And they're for asymptomatic? The QuickVue and the BinaxNow are both asymptomatic? FDA EX OFFICIO: Yeah. In order to authorize for both direct-to-consumer consumer and over-the-counter, you're not being a requirement for a prescription, we do recommend that the test has been validated or authorized for screening asymptomatic individuals— CLIAC MEMBER: OK. It'll be on— FDA EX OFFICIO: --because when it's purchased by the consumer, they can use it on whoever, for whatever reason. And so, we recommend a bit more validation for those. Or in the case of both Binax and QuickVue, they have agreed to a post-market study to show that the serial testing in the home-- so both of these tests will be provided at least in a two-pack and ask that the consumers test themselves on day one and again by, say, day three in order to ensure-- and all it takes is one positive result, and it's positive. But if they're negative, they should do the second test on the second or third day, just to make sure they're negative. CLIAC MEMBER: OK. And so, has there been any talk for the US to do, as other countries, to provide this without a cost? As a public health offering, has there any discussion around that? And if not, where should we go to help make that happen? Because the poor can't afford this. The homeless can't afford this. How do we help get this into everyone's hands? FDA EX OFFICIO: So that's not a decision that the FDA makes. It's made above the FDA. And perhaps the CDC or my CMS colleagues have other thoughts. But this is really an administration and/or congressional decision to do this sort of

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thing and provide tests in this sort of way. But there certainly would be no problem from an FDA perspective in doing that. These tests appear to be accurate, easy to use, and inexpensive. CLIAC MEMBER: OK, great. Thank you so much. CLIAC CHAIR: Thank you. In order, it will be [CLIAC MEMBERS]. CLIAC MEMBER: Yeah. And my understanding, [CLIAC MEMBER], is that all of this COVID-19 testing is free of charge, really, to anybody. But I was just going to put my clinician hat on for a sec to say, I think one thing maybe we didn't-- I mean, as important as tests like BinaxNow are and those sort of things, to put these things in patients' hands, the one thing that may not have been thought through too much is the attacks that that can put on a primary care physician's office. So, if somebody does this at home, they get a positive result, who do they call? They call their family doctor. There's no compensation there. There's no-- so a lot of folks are telling those folks, at this point-- having done a lot of pro bono work, I think they are saying, OK, well, let's get you set up for a telehealth appointment, and we'll go through all of that. But I wonder. Again, going forward, is it a possibility that that could be part of the thought process, too? Is that, through CMS or whomever, that we could get some coding for clinician interpretation of these types of at-home tests when patients don't know, what does a positive mean? Well, let me spend a half hour telling you about it. So just a thought. CLIAC CHAIR: Thank you. Great thought. CLIAC MEMBER: Thank you, very interesting. And I really appreciate hearing about this. I really like the theory. And I like the idea that something like this could be rapidly made available for the next pandemic. But I do have some concerns. My biggest concern evolves around the issue of, what does someone do if you get a discordant result? [CLIAC MEMBER] just mentioned they would contact their physician and maybe do a telehealth appointment. But that doesn't get you a retest. So, if you have somebody who's a positive, but it's a false positive, they're not going to know this. And is there a system in place where a discordant result is recorded and tracked, how often this occurs? Because I know, from my experience, that you want to follow up on what the cause of the discordant is. And when we're talking about a cutoff of 80% sensitivity, that's excellent when you have a lot of disease incidence occurring. As the incidence declines, which it will-- and these tests will still be sold, and people will still be testing themselves-- that predictive value is going to be extremely low. And that's going to lead to further testing needs. So, I think that there is great benefit to it. But it shouldn't be around when incidence is low, because it could lead to a lot of misinformation out there. CLIAC CHAIR: Thank you. CLIAC MEMBER: OK. So, I was just going back to the questions that [CLIAC EXECUTIVE SECRETARY] laid out about the expense, and the self-collection, and so on. I got a lot of notes here, so I'm not sure I'm going to be able to put them back together. But I think the point is that as we talk about this, we need to reach out to really non-traditional customers, if you will. [FDA EX OFFICIO] said they're purchased by the consumer. And they're used by whoever and however they want. That's true. And they're accurate, easy, and inexpensive. But we know that sometimes the reality is they're not. And people use these tests in ways that they probably shouldn't. So I think it's important for all of these to make sure that the consumer knows. And so the question is, have we done a good enough job? I think there have been efforts at this. But I think we need to reach out to all the specialty societies, from the professional side the AMA, the nurses, et cetera, for patients I think through public health, the Facebooks, the Twitters, the Choosing Wisely, the AARP, et cetera to work on that. We know that people, for example, use home glucometers in very interesting ways and ways to cut corners. And that can be a problem. But this, when it's done wrong, has public health implications as well. So I do think that, in terms of the application, what CDS, CMS, and FDA can do to fill the gaps-- I think we need to do a better job of finding more and more venues for non-traditional education for people by use of tests. That's really what we've seen. CLIAC CHAIR: You commented you had pages of notes. CLIAC MEMBER: Yeah. Yeah. I just condensed it so that others can talk. CLIAC CHAIR: OK. Thank you. CLIAC MEMBER: Yes. So again, I'm sorry, [FDA EX OFFICIO], I'm going to ask this question of you. But we've talked about tests for surveillance, tests for screening. And also, you used the phrase, without a prescription. And the confusion or the difficulty that I have is that we operated a large number of drive-through screening-- let's call them clinics-- where it wasn't really clear who the ordering physician was, because none of the individuals who drove through had been seen by a physician prior to their arrival. Now, how does the FDA view that? And I just may add is it regulated, in your mind, at the federal level or at the state level? Because I've got a number of law students researching across the country how various

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state legislatures view the issue of testing on demand, or testing on appearance, without physician prior examination. So, I'm sorry if that's too broad, but it's really focused on the issue, of what really requires-- when is a physician pre-examination required to perform a test? FDA EX OFFICIO: Well, the FDA decides when a health care prescription is recommended for as a mitigation. And as I said, we allow point of care and even home tests to be as low as 80% sensitivity. And prior to recently, most of those were prescription-based home tests, because of the involvement of the clinician is a mitigating factor. When we make an authorization, there's a little symbol on the authorization, a little RX symbol, if a prescription is part of the authorization. Test developers can therefore not promote a test without a prescription and cannot sell into situations where there is a physician or a clinician prescription capability. When we have other mitigations to reduce the risk of false results, we allow over-the-counter or direct-to-consumer. And then what health care facilities, and clinics, and other settings do with a test that is a prescription-based test and how they act is not something that the FDA actually regulates. And it's not in our purview. But my understanding is that there are oftentimes state and local laws governing prescription and that there are some states that don't require a prescription for this sort of thing. CLIAC MEMBER: Very good. Thank you. I think that was very important to get that in the record. CLIAC CHAIR: OK, [CLIAC MEMBER] has popped up in the chat box. And he has two comments, one about reimbursement. And the second is about the magnitude of the false positive issue in home testing. I'd like, before you go-- and [FDA EX OFFICIO], I'd like-- and it's probably not you. I would like our governmental partners to discuss the inequity that currently testing done by clinical laboratories or other entities not at home are not charged to the patient. That's very, very clear. So, from the patient's perspective, it is viewed as free. When we go to home testing, that today means the person purchasing it is having the cost. And that's a little bit unequal. So, I'd be curious in [CLIAC MEMBER] comment. Is there a possibility of distribution of these kits in pairs at no cost to the end user? And then, [FDA EX OFFICIO], I'll let you talk about your second point. FDA EX OFFICIO: So we'll have this reimbursement discussion first. And then I can talk about the second point. OK, go ahead. CLIAC CHAIR: And I— FDA EX OFFICIO: Or do you want me talk about the second point? CLIAC CHAIR: No, as I believe you said you could not comment on the reimbursement. So, I'm not sure who can. FDA EX OFFICIO: Oh, well, actually, did I? CLIAC CHAIR: You said, I don't believe I --- FDA EX OFFICIO: I can comment, because it's my understanding that home testing is not currently reimbursed. And it's a legal thing. It's not a CMS administrator decision. CMS should weigh in. But I know that it was discussed that all testing is free to everybody in the country. And I don't believe that's— CLIAC CHAIR: That's right. FDA EX OFFICIO: --fully the case. CLIAC CHAIR: That's right. FDA EX OFFICIO: But [CMS EX OFFICIO] or [CLIAC DFO] may have other additional information to add. CMS EX OFFICIO: From a CMS perspective, and dependently on this, reimbursement for home testing is not decided by CLIA. And then I'm sending in a check. Then there's another division within CMS that we're referring you to. CLIAC CHAIR: And [CLIAC DFO], I saw you popped up. Did you— CLIAC DFO: I do. But unfortunately, I do not have anything to add on this. I'll stop. CLIAC CHAIR: So—

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FDA EX OFFICIO: Yeah, I don't want to be speaking for CMS. Yeah, there are different parts of CMS. And [CMS EX OFFICIO] is from CLIA, and there's the reimbursement portion of CMS, too. CMS EX OFFICIO: Yeah. We'll add this information in the chat for everyone. CLIAC CHAIR: From a very simplistic, my perspective, reimbursement involves a couple steps. If we really want to get home testing out there and widely used, we should just be giving out the test. We don't even have to deal with the reimbursement. But that's a really simplistic view. And then, in terms of what do you do with the test result, back to Chip's comment. Could that be somehow, how are the instructions improved? Is there a hotline to call? Is there something to not put the burden back on the individual provider? But I'll let y'all chew on that. And then, [FDA EX OFFICO], if you want to talk about the false positive issue, we'd love to hear about that. FDA EX OFFICIO: Yeah. I mean, it's something that I did the calculations relatively early in the pandemic and have continued to be a staggering, to me, calculation. So, while these lateral flow tests that we've authorized, both point-of-care and home, are quite accurate and surprisingly accurate, there is a false positive rate. And based not necessarily on the evaluation data, which is minimal that we see, but based more on real-world data and evidence that we track, I estimate that a given good authorized lateral flow test will have a 2% false positive rate. That's 2 out of 100 will have a false positive. They don't have SARS-CoV-2. And so, if you just test everyone in the US once at home-- so that's 330-odd million testing opportunities-- the math says that you'll have 6.6 million false positives per month. Currently, I think the estimate right now is we're seeing new cases detected at 70,000 a day in the US. Times 30, that gives you 2.1 million positives a month. So, the false positives, if we were to scale up and test everybody once a month, would quadruple the positives that we see. 3/4 of them will be false positive, if my math holds. And that's a lot of positives to follow up on, and do repeat testing on to confirm, which should be done. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, as it relates to what [CLIAC CHAIR] is talking about, we need to involve the public. That's how we have really messed up here in the United States, is that we haven't involved the public in this massive challenge that we're going through. And so, if we had tests that we can test ourselves at home, and we get a positive, we either test one more time with these very low-cost tests. Or if it's positive, we test ourselves again with these very low-cost tests. And if it's still positive, then we go to these facilities that will then be recording the positive or the negative test, the higher level of tests. So, this would be like-- think about it as screening at home. We would be screening ourselves often at home. And if we get a negative and we have symptoms, we test ourselves again. And if we get another negative then, OK, we don't have it. It's twice. But if you have symptoms and you have a negative, you need to test again. I mean, this is the obvious-- is, I have symptoms. I could test myself really quick, because then I could find it if I can go to my son's ball game or not. These are the things that we need to start doing. And I sent a website called rapidtest-- T-E-S-T-- .org. These are public health experts, many people, that are focused on this. There are papers after papers after papers that are justifying this simple step into us getting out of this pandemic. It's not forever. It's what we should have done a long time ago, what health care workers have been crying for. Please let me test myself before I go home and take it home to my family. It's people, teachers at school. Please let these students test themselves right before they come into my classroom so I know everyone's safe and can be free to learn. This is not so difficult that we can't find a way for our country to start ending the deaths that are happening now. And they will continue to happen, if people aren't more involved. As it relates to how do we educate the people, CDC is awesome with educating the public-- and so is CMS-- about simple steps of, here's how you use your package. Create a user group that people can go into and ask questions any time of day. CDC is excellent with these kinds of campaigns on how to educate the public. And just like what we've done now, many times doctors aren't involved in what's happening when you have COVID symptoms. You're going to a public health solution that's happening. You're not always going to your doctors right now. And now that we have telemedicine, we have reimbursements for patients to meet up with their doctors online. So that whole issue of, too many doctors will be contacted with this, it doesn't even make sense. We now have a way for doctors to get paid for time on the phone with patients if they've received a positive. I mean, this is just basic 1A. The only way to get out of a pandemic or stop the spread is to identify those people that are carriers, isolate them, treat them, and then find out that they're OK to enter into public life again. So, this is just basic infection prevention we are not doing today. We need to do it. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yes. Hi. How are you? Just in response to the first question that's on the screen, and then also reflection back, and some of the concerns that were raised on this discussion so far. Particularly regarding the concerns about what happens after someone who is self-testing at home or self-collecting at home-- after they get a result, where do they go? How do they get support? First, I just wanted to call out that this industry already exists. I think the models are twofold. There's one that we have already discussed, is the direct-to-consumer model, where the consumer can purchase a test, and test, and get a result. And this is all something that's done at home. But then also, similarly, there's the

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consumer-initiated test. And it's slightly different, where the consumer is already looped in with the provider or a health care provider before moving forward with that test. Not that-- in terms of the protection on the backend after a result, I think the consumer-initiated is somewhat safer because, again, you have that pre-connect with the provider where, in the direct-to-consumer setting, the consumer will have to then identify a provider that would be willing and able to answer questions that they have. But my point here is that, either way, I think there should be a way to engage with health care after a result. And so, to that first question is-- where there are potential gaps in guidance, I think it can involve particularly around that component. What happened after you get a result? Another call-out I wanted to share is that, throughout this pandemic, obviously a lot of health care was converted to telehealth. And telehealth has exploded in this past year. And it is very much likely here to stay. So, I know we're focusing very much on the pandemic and testing for SARS-CoV-2. But I suspect that many of these conversations we're having today, we're going to be having them for a very long time as telehealth remains with us. And of course, diagnostics-- we've all heard the quote, 70% of all medical decisions are based upon laboratory tests. So, I think this concept of point-of-care, self-collection, and self-testing is only going to grow as we move forward. So just think thinking through this now is certainly something that's extremely timely and extremely important as we move forward to protect consumers, and also just meet the needs and expectations of Americans in this new world of health care. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I just want to insert. Is there a role for artificial intelligence in between the consumer and the telehealth provider? And I'm thinking in particular for communities that don't have written languages-- the Halang, Salang. I'm thinking about, how can we do user-friendly ways of explaining in ways that don't overburden our human capital? So [CLIAC MEMBER], you're up next. CLIAC MEMBER: Thank you. Yeah. So, I think one of the real values of having adequate testing-- and particularly, I think Tim was talking about doing tens of millions that-- the government, I know, has bought the first $150 million BinaxNow cards. And those are going to schools. So, the numbers are getting big very quickly. And I was just wondering about how we're going to track the positives now that we've got this huge deluge of tests out on the market. One of the real values and the advantages of testing is surveillance and figuring out where the virus is going to go next. And maybe even, at some point, these tests will be able to show us variance. I don't know. But it just becomes a huge issue in terms of tracking positives. And who is responsible for that? I know the BinaxNOW has an app that will-- once you put it in, it gives you the positive or negative. And so certainly we could use artificial intelligence to map out where those positives are happening. By using the app would be one way to go, I guess. But I don't even know if that's going on right now. But it certainly could be a use of that technology, I would think. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. There are a few home devices with connectivity. But that's predicated on the home having connectivity. And we know that doesn't exist. So, the lineup is now [CLIAC MEMBERS]. CLIAC MEMBER: Thank you. First of all, I want to thank all of the presenters for this excellent information. I listened very carefully. And of course, it is very important information and brings me to the point of wanting to comment on the collection of the specimen and how sometimes you can have a number of false positive, negative. And I'm wondering, in that regard, do we need to look at CLIA, do we need to review the guidelines for collecting, not only the specimens in home and the home collection, but also at the point of care? I have personally experienced the fact that sometimes the technician will almost gouge your brain out going up, rather than going down. I'm just talking about personal experience. And so, it seems to me, do we need to look at that information? And I know a great deal of information has been presented in reference to a query in that particular area. But we can discuss at the end when we're looking at recommendations, is that an area that we need to take a look at, especially for those areas that I mentioned-- at home, a home collection in the home, and point of care-- and particularly the point-of-care. CLIAC CHAIR: I don't know if [FDA EX OFFICIO] wants to comment. There certainly has been part of this with the EUA submissions. And I do know states have licensure requirements about what level a person is allowed to do an MT, versus anterior nares, versus mid-turbinate nares. So, I was wondering if [FDA EX OFFICIO] wanted to comment on that, on the evidence that shows test performance on these different collection types, different collection people. FDA EX OFFICIO: Yeah. We haven't necessarily-- so first of all, NP swabs require a skilled person to do. It's just a little bit too risky for anybody, other than someone who is skilled. We get MDO reports on a weekly basis of the NP swab tips breaking off, and then an otolaryngology consult to get it out. And we do not authorize self-collection with an NP swab. We will allow self-collection of a mid-turbinate, and obviously the nasal swab. We also don't authorize an oropharyngeal swab, which has been authorized for some tests, to be self-collected. And early on, when some developers wanted to do that in the home, we saw some safety signals. And we just shot that down, as far as self-collection goes. If you look at the accuracy compared to NP swab, NP swab still is largely the gold standard for getting an accurate result, the most sensitive result, if that's important. But we've looked at comparative studies on the same patients where you do mid-turbinate, a nasopharyngeal, and an anterior naris. And anterior nares and mid-turbinate offer a good way to test without dropping sensitivity too much, and obviously a lot easier to obtain, a lot safer to obtain. They can be self-collected. And

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there were times when NP swabs were in short supply. And an anterior nares swab was very welcome by all. Hopefully, I addressed the question in some way, shape, or form. CLIAC CHAIR: [CLIAC MEMBER], did that answer your question? CLIAC MEMBER: Yeah, thank you. Yes. Yes. It's just an area that I'm really interested in. I think it's really important that we just take a closer look at that particular area, in terms of collection of the specimen, because what I'm seeing and have experienced would support what I'm hearing today. Thank you. CLIAC CHAIR: Comment to panel members, please do not use the chat box for your sidebar conversations. The public cannot see the chat. But moving on, the order is [CLIAC MEMBERS]. CLIAC MEMBER: Good afternoon. So I got a couple of comments, mostly related to the idea of having these positives out in the community, and then saying that it would be easy to have these tele-visits with physicians or nurse practitioners, because the reality is that it wouldn't be that easy. It would be extremely difficult, because we're already drowning with a lot of those tests that are being done, even just with the pop-up clinics. We were offering antibody treatments through the EUA from the FDA on the outpatient side. And during one conversation with a patient that was maybe two minutes long, I would miss 50 calls from patients who were trying to get signed up for this antibody treatment. So, I think that we really need to think about that and be a little bit more thoughtful about that. The other aspect of this that I thought about-- when we're considering how we would actually track this, we could add a QR code to these tests, something similar to what we've done with the vaccine, and have some program, like the V-safe program, where you're automatically enrolled in this bot that asks you, was your test positive or negative, or instructs patients that if their test is positive, then they go ahead and follow these steps. And that way, we can at least triage patients or triage the public into different queues and into providing them with different solutions based on maybe their comorbidities, or their age, or things like that. So if you were greater than 65 years, that would put you in a queue where you might get funneled to someone who could talk to you about antibody testing-- or, I mean, antibody treatments, or something like that. So, I don't know what the success or what the results have been with the V-safe program. And perhaps, [FDA EX OFFICIO] you could speak to that if you're aware of it, because I think that the FDA is running that-- maybe not. But if those results have been promising, then this could be something that we could consider for this point-of-care testing. That's all. FDA EX OFFICIO: I am not familiar with that. So, it's not being run out of my office. Maybe other people are aware of it. CLIAC MEMBER: It's not— FDA EX OFFICIO: V as in vaccine? V as in vaccine, you're saying. CLIAC MEMBER: Yeah, I was. Any time when we're giving the vaccine, there was a QR code. And the CDC-- or I don't know if it was the CDC. But you would get a follow-up prompt. And then they would follow up with you daily for the first week, and then weekly for the first eight weeks. And now I think it's every month or so. And they're just collecting data on adverse events, things like that. And if no one else is familiar with it, then that's probably an issue, because everyone who's had the vaccine should have signed up for this. So that may be a testament in and of itself. CLIAC CHAIR: Yeah. And [CLIAC MEMBER], I will comment. In California, the CARES database where we track vaccinations has crashed multiple times. So that is an issue. V-safe, we are aware of. But I want to again mention there are entire communities who have no connectivity. Or there are communities fraught with fear of being identified and traced who will not want connectivity. CLIAC MEMBER: Absolutely. But I do think that this will be a multi-prong approach, where we're going to need different ways to connect with different types of-- Yes, wonderful-- different ways to connect with different populations, with young people, and the elderly, and people who are institutionalized, and so on, and so forth. So, I think that that provides maybe one way to track these results. CLIAC CHAIR: Yes. And hoping for creativity to identify multiple ways to get the best benefit as we think about equity and inclusion. So, thank you. CLIAC MEMBER: Yes. As we're having all of these conversations, particularly I was struck by [FDA EX OFFICIO] comment on the preponderance of false positives if we ramp up testing, given even a very small false positivity rate. And that really made me think about the need-- we want to make sure that all of the providers, as well as the patients who may be doing these tests at home, are getting the appropriate educational materials. And I think a large proportion of that is just talking about statistics in general for a lot of these tests and breaking it down into easy-to-understand understand terms. Because, for example, a very small false positivity rate is OK if you're doing, as we say, 10 or 20 tests. If you're

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doing millions, it becomes huge. The converse is true for a lot of these clearance to go out into the world home tests that I think a lot of people will be looking for. We would really be more worried about the false negatives. And a lot of these screening tests do tend to have a lot more false negatives. And I think that's the kind of educational material that may be missing in some of these discussions overall. And so, it's not just talking about having access to the tests. It's also increasing just the general health of literacy. And I think that's out of the purview of this group here. But I think that's an important conversation to make because, for example, you're now talking to friends, family, some very educated people. I know very early on in the pandemic, where people were looking for things that could help them, one of my friends found this random news article that's like, oh, this hospital has a 97.9% survival rate for COVID. I'm like, that's literally the inverse of the natural progression of the disease, which at that point was a 2% death rate. So, it's really helping people at home as well as the nursing care providers who are having to screen all of their patients understand what the metrics that they are testing on is based off of. And again, not necessarily directly an answer to any of these, but I think that's a really valuable block that also needs to be deployed with access to how to use these tests. It's really how to understand what kind of result you're getting. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, I have to say something about V-safe as an obstetrician/gynecologist, even though I'm not currently practicing, but certainly as part of my community. It's been incredibly important. That's how they've been monitoring women who are pregnant getting the vaccine. So, whoever is on the call who is even remotely involved with that, thank you very, very much. And you mentioned the V-safe, because-- I was going to bring that up as well. And this speaks to, I think, [CLIAC CHAIR] point about AI and what I was trying to say before in terms of modernization, updating technologies. For example, getting electronic health records going-- that is actually a government effort. It keeps coming back to that. A lot of these problems, there are technologies that could really help. And that is-- it's a big project, but it keeps coming back. We don't have the human power to handle a lot of what is happening. It has to do-- as I mentioned before, in terms of communication-- how we connect and communicate with each other. There are ways to do this. And just the technologies itself might be a project that's worth perhaps looking into. But yeah, V-safe is voluntary. But the fact that it's so-- it's like, get vaccinated, get your smartphone. It's actually built for the phone. And I think that probably is the most important thing. People are on their phones. So, I don't know if we can make a recommendation or something around just looking into technologies. But going back to [CLIAC MEMBER], finding out what's out there that we should be accessing. CLIAC CHAIR: Thank you. CLIAC MEMBER: Hi. I just think something that we can't ignore is the human factor in all of this. And when we have the public with home testing self-collecting, definitely something that we've seen with the testing is that the testing is so very sample dependent on the quality-- you get a good test with a good sample. And I think that, when we consider self-collection and self-testing, that's one thing that we have to consider in our recommendations-- is that education is very important in all of this. And when we have patients self-collecting, they're only going to get a good test if they get a good sample. And what is the intent of the testing? We have patients that get tested for a variety of reasons. They're testing to travel. And they can only travel with an official test. So, there are all kinds of requirements that go into the test report that they have to provide. So, with this home testing, is this going to serve as an official test? Or is this a screening test for surveillance and for use to identify a positive or home? Or how is this test going to-- is this going to serve as an official capacity in that way? I think I would have some concerns about a negative test that was home collected, and maybe some of the motivations that might go behind that. We have people that are really concerned about being able to work. If they home collect and provide that official test as a means for being able to get back to work, even you might have some implications going behind home testing and being able to provide that as an official report for some of these. You might have some downstream effects to that. And then I also want to echo some of the other points that have been made around education. I definitely get some patient questions that make it through to my laboratory. And people get very confused about testing in general. Definitely, we have high-level conversations. And we work with our providers daily in what do some of these scenarios mean-- retesting, reinfection, co-vaccination, positivity. So, to expect a layperson who is testing at home to understand all of this without someone to go to, I think that's a lot to try to-- a big bite to bite off. I'm done. Thank you. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, [CLIAC MEMBER], specifically-- if you want to think about what is happening today, all we have to do is take a look at the NFL. They created a bubble. They were able to have their games in play, because they had the money to test their players and the people that were going to be in the room-- same thing for basketball, same thing for rich people going to parties. This is happening today. People are living their lives freely, the people that have means. The people who don't have means, don't have the tools-- this is about equality and equity in health care. Naturally, there's going to be-- there will be people that don't want to do this. They don't want to test themselves. They don't want to do it. That's fine. There's going to be probably 50% of our nation that doesn't want anything to do with it, because they still don't

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believe in COVID. We need to affect our nation the best we can. And we are missing a huge piece of the population by not spending the funds that were approved for the Rescue Act on providing self-tests for those people-- like health care workers, like people who have a cell phone that have no problem testing themselves. Of course, there's all different kinds of people in this nation. But we know how to test. Think about a birth control test. We can easily test ourselves. And that's why we have the FDA, because they're helping us find these tools that people at home can use. And then we have the CDC who knows how to educate the public. And CMS-- they know how to educate the public. So, don't think of every 330 million people. Don't even think of half. But think of a major part of our population that now can become a part of the solution to stop spreading this virus that continues to spread daily, even if we have vaccines. CLIAC CHAIR: Thank you. I'm going to have [CLIAC MEMBER] make the final comment in this session, because I want to direct us back to the questions on this forum. CLIAC MEMBER: OK, thank you. Yeah, quick story. Jim Nichols-- who used to be on the committee and, many of you know, is a point-of-care expert-- a number of years ago took his son to have a beta strep test. He told this story. And in the doctor's office, the nurse did the appropriate swab, and then went to the device and inserted the wrong into the swab in the device in front of him. And I think it illustrates how people who design assays can't be creative enough to figure out how the public can misuse an assay and get the wrong answer. I thought it was an amusing story. There are others. But just some quick comments on low-prevalence testing-- I think that's a huge problem. My personal belief is that mass screening is probably not practical to totally solve our problems in the country. All tests will have false positives. Test challenges are the absolute worst in low-prevalence populations, as several have stated. It varies with assay performance. And I think really the use of tests in those situations need to be tailored to specific scenarios. A football team may be one of them. There probably are some other uses. But when we first began testing in our area, I think there was a lot of public misinformation. And testing sites were flooded with people who had no symptoms whatsoever. And they were thrilled that they were negative. So, I think those of us that are doctors would say, that's great, you're negative today. I mean, what about three days? What about a week? What does that mean to you? What does that mean in terms of your life going out in time? And so, I think that those are situations where it's important to have professional input. I think ad-lib public testing may have adverse consequences if it's not properly understood by those involved and the test performances or not known. And finally, I don't think testing can replace the other mitigation efforts in vaccinations, because those are ongoing. And they do work-- inconvenient, but they are helpful. So just my opinion. Thank you. CLIAC CHAIR: Thank you. It is 1:40, which is 4:40 your time, which means we have 15 minutes left. And I'm coming back to the questions. Do we have responses? Do we have any ideas for these issues, whether or not we want to make any recommendation? And before you all launch into that, remember, following this, we will talk about future topics for CLIAC. And then, finally, we still have a half-baked recommendation from the first session out there for discussion. But I would like to focus on this subject right now. And [CLIAC MEMBER] is the first out of the gate. CLIAC MEMBER: I've been uncharacteristically quiet in this meeting. And I think I've been struggling with a lot of the content of what we're trying to achieve in this. I keep having a hard time knowing, what is the clinical laboratory improvement purview and oversight? And what is an overreach? Which I always hesitate for government-level overreach. But I was looking at a question four. And I was coming back to the earlier comments of Dr. Andersen from ARUP about the-- at some point, our homes became labs, under wording. So maybe it isn't so crazy that we have some oversight of our home testing because, if the pathologists are supposedly in the lab when they're signing out cases, then the layperson performing a test in their house is de facto in a lab. And I'm going to make that provocative statement and let the fire burn. CLIAC CHAIR: You've stunned us into silence. CLIAC MEMBER: It's my parting gift. CLIAC MEMBER: Yeah, that was a good one. No, I'll just comment, because I do think it's important to appreciate that there are regulatory structures in place to allow testing at the home. I mean, over-the-counter testing has been around for a long time with glucometers. And I think it's just important to recognize that there are mitigating measures that could be put in place and have been put in place to ensure safe at-home testing. I agree it's different than in-lab testing. But I think we've already proven it's possible to do it safely at home. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. [CLIAC MEMBER] has agreed with [CLIAC MEMBER] comment in the chat box. And then the line is [CLIAC MEMBERS]. CLIAC MEMBER: So to the points-- thank you. To the points that we're talking about, as far as point-of-care testing-- I think someone already made this point. I wanted to emphasize this. I think it could be a role of the CDC, or maybe another agency. When this point-of-care testing, either at home or in the nursing homes, wherever these antigen tests were used--

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we really weren't collecting that data. And I think that, from an epidemiologic standpoint, we need to figure out how we can correct that issue and make sure this testing is going to take place in those areas. How can we get those results back? Because one of the things that I thought was great with this-- and there was some confusion in the beginning as to where the data was going to flow, and who was going to collect it. But I think, with these antigen tests we need to ensure that the data is getting back to state, CDC, and others so we can use it for this epidemiologic purpose. CLIAC CHAIR: Thank you. CLIAC MEMBER: I want to add on to [CLIAC MEMBER] comment, and others, about the data. So, one thing I think we've learned with this pandemic is that if we could trust everyone in the United States to do the right thing, both rich and poor, we would have all been wearing masks. And we wouldn't have had what we have. So, I know there are people who will get a home test and want to go to a party, or want to go to an event, or a home show, or buy a car. I don't think-- I think that we need to strive towards something like Livongo for diabetes, where you're doing home testing, but that little device ports up into the cloud. So, if I overeat the night before, I can't change my glucose result. And I think that's an important critical piece that-- I mean, we don't even have cloud upload yet. But it's going to have to happen if we're going to rely on the home testing. There are no negative consequences for anyone who lies. And I don't want to be that person. However, again, I take it back to the masks. All we all had to do was wear masks, really, and follow hand hygiene and social distancing. So, I've learned not to trust everybody in the United States. And I think that that is something that I would not have said a year and a half ago. I would have been like, oh, sure, people will report, they don't want to get their family sick or their neighbor sick. But I'm not so sure now. So, I think that we really need to focus on the requirements for-- and if the diabetes community can do it, it can be done. So that's just my thoughts there. CLIAC CHAIR: Thank you. CLIAC MEMBER: Thank you. I'd like to see the committee consider recommending the FDA track discordant results on these, have a mechanism for reporting discordant results, so that we can at least know how the performance is through time. Otherwise, it might get to the point where people are not doing any more than flipping a coin. We saw that with influenza, Rapid A influenza test years ago. So, I would like to make that recommendation for us to consider. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yes, two points-- first, on the at-home test. The horse is out of the barn, as far as those are concerned. I think we all made the point that doing one test so you can go out to a party and be around others is not the same thing as being in a bubble and having serial testing that occurs. And people are making those decisions. But it's going to happen. So, my first point is-- I think that it was [CLIAC MEMBER] that said, we just need to be really clear in those tests inserts to the public. This is what you got. And if you're symptomatic, you got this chance of predictive value. And if you're asymptomatic, you got this predictive value. The test isn't perfect. Don't ignore the mask rules, as [CLIAC MEMBER] just commented on, based solely on this particular result. Just really instructive-- I think that's all we can do with the at-home test. Going to the waived testing however, in the professional settings, as [CLIAC EXECUTIVE SECRETARY] touched on, this has long been a sore point in the testing community-- that it essentially is a passport for no oversight. And I, personally, think that that's problematic. And if there is some way that we can work in an oversight-- and I know it places, as I commented before, a burden on CLIA. But it may be-- as we've all said, if you're going to ask for money, this is the time to ask for money. This may be the time to get some sort of sampling. Maybe 30% of waived labs get surveyed, something along those lines. But I think people-- and granted, the Joint Commission and the hospital will look at them, the Joint Commission and the various programs. But those are not laboratories that are doing those surveys, either, in those particular settings. So, I think some sort of oversight mechanism for the performance of waived testing in health care settings is prudent. Thank you. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. Before [CLIAC MEMBER] speaks, I do recall CMS, for many years, ran that 2% look at waived testing-- I hope I'm correct on that-- and have some preliminary data. But that was before SARS-CoV-2. So, while you're all thinking about that, I'll let [CLIAC MEMBER] give his comment. CLIAC MEMBER: I was just going to respond to [CLIAC MEMBER] that I agree the interpretation needs to be clearer to the end user for at-home testing. But-- and I'm going to make up a statistic here, like the 70%. I'd say 90% of the physicians I consult with don't even know what positive predictive value means. So, trying to-- my parents wouldn't know what that means. So, I just don't think we could-- I don't think you can distil it down to the lay population using those terminologies. I think it has to be completely rethought how this is being put out in the marketplace. When you think about the OraQuick HIV test, it's says, if you get this result, call this phone number. And then you get the consultation. But getting back to [CLIAC MEMBER] comment, there's not enough humans to consult on this. So, I think it-- we all have the right ideas. I just don't think we have the resources.

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CLIAC CHAIR: Yeah. And I'll just comment. So, I'm in the workplace. And I have a lot of questions for my staff who a family member will test positive. And it's a congregate setting. And actually, I find the most valuable answers are coming from employee health, where they're factoring in whether or not the person was a vaccinated exposed person, and whether or not the exposed person is symptomatic. So, it all is much bigger than the test result. And in trying to interpret this home result when you're living with family members, some of whom may be symptomatic-- I think it's bigger than the lab. I see [CLIAC DFO] has popped up with-- ooh, you want to talk about it, [CLIAC DFO]? Because-- no, he doesn't. OK, sorry. Don't use the chat box for side conversations. We do have two comments up there for consideration to send forward as a recommendation, the first to determine a mechanism. And again, I have this remote memory of CMS conducting prior surveys to look at quality performance with waived testing. So, do we already have a process that has been used that could be revisited to see if the date is different today? And then, second-- a very specific recommendation that the FDA track the discordant paired results. It's phrased as point-of-care test. Did we mean point-of-care? Or did we want to frame it as SARS-CoV-2? I see my point. Where's my point. CLIAC MEMBER: I would like to see all point-of-care tests. CLIAC CHAIR: And so discordant results would either be paired point-of-care results, or would be a point-of-care versus a lab result, right? There are a couple pairings on that. CLIAC MEMBER: And that's an interesting point. I'm not one who believes that you should repeat a test with the same method and then rely on the results you like. It doesn't make sense to me. I always think that you should compare it to another test method. So, in this case of a point-of-care, that would be a lab test, so a point-of-care test that was discordant to a lab-based test. CLIAC CHAIR: I would say many of us probably already know this discordant, right, then relative to SARS-CoV-2, because it is not uncommon for a point-of-care test to have a sample submitted for a lab test. And in my little world, our discrepancy rate fits perfectly with the nonperformance in the IFTs. So, there were no surprises there. So, it's open for conversation. Does anyone other than me remember the previous presentations, probably around 2006, I think, from Judy Yost's group around waived test sites following manufacturer's instructions? CLIAC MEMBER: I remember. CLIAC CHAIR: Thank you. I think I'm losing it. So, I know there was a process. And I know it was labor intensive. CMS EX OFFICIO: We do have a previous study for Certificate of Waiver labs. And we would have those results and can make those available. CLIAC CHAIR: And is the request from— CLIAC EXECUTIVE SECRETARY: I was just going to answer too that there are-- as a starting point, we included a background document that's posted on the website that has the previous CLIAC discussions on waived testing and recommendations. And those CLIAC discussions would include all of the former CMS presentations. And we could also go back through our CLIAC records and pull out the ones that have those presentations. But it would have been-- yeah, it was in the early 2000s that there was a lot of attention being paid to that. CLIAC CHAIR: Thank you. [INTERPOSING VOICES] CLIAC CHAIR: I'm sorry, go ahead. CMS EX OFFICIO: In particular, a certificate of waiver project took place from 2002 through 2016. CLIAC CHAIR: Thank you. And I remembered it showed improvement over time. And the biggest gain was with the testing sites following manufacturer's instructions, initially lower than hoped for, but then really improved. [CLIAC MEMBER], you have a comment? CLIAC MEMBER: Yeah. I just was going to comment that the Joint Commission does have standards, as I mentioned, in all the health care settings that they surveyed. And those are publicly available, what the findings are, and what the quality deficiencies are detected. And I thank you when you say that they went through 2016, because I was at the Joint Commission through 2013. And I remember doing a few dog and ponies-- I think maybe for CLIAC, but certainly for some other laboratory programs-- looking at the findings from the hospital surveyors versus the lab surveyors, and what things

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laboratory surveyors picked up on in presumably some of the same organizations, versus what hospital surveyors would find. But that would probably be some of the better data right now about what findings are out there, because we do know that that is the one organization that is uniformly reviewing the waived testing. CLIAC CHAIR: Thank you. CLIAC DFO: Thanks, [CLIAC CHAIR] Now I'm ready. So, I just wanted to try to pick up on a couple of threads. I do appreciate [CLIAC MEMBER] comments about, where is the extent of our role here? And I think it is fair to re-emphasize that CLIA doesn't apply to over-the-counter testing. FDA, obviously, needs to authorize tests that can be used without prescription, and at home, and outside of CLIA settings. But I guess I'm particularly interested in perhaps trying to focus the conversation around the waived tests or point-of-care testing. And one of the things that I've really noticed over the last 15 months is the wide variety of complexity in the point-of-care tests. And I'm not questioning FDA's decision making around the complexity, because I think in general all these point-of-care test compared to the laboratory based or moderate or high complexity tests are simple. They are straightforward. They are relatively easy to use compared to the laboratory-based tests. And for people, I believe, with testing background, these point-of-care tests are straightforward. But I'm really concerned, based on a lot of the experience that we've seen with the antigen tests that were initially rolled out last year, that they were for people who are brand new to testing and point-of-care testing. Despite our perspective that they're relatively simple, they were hard to use and proved difficult. And I think we did see a lot of examples of false positives and cross-contamination with the initial roll-out of the antigen tests that were based on an instrument. The antigen tests that are card-based that we see much more of now are much easier to use. And we've seen a much, much lower false positivity rate. And yet both of those test classes are classified as waived tests, or basically low complexity. And it just seems to me that we have a challenge in that not all waived testing is truly simple. And as this community expands significantly, I believe we're going to have more problems with the way these tests are used by a relatively inexperienced community of point-of-care testers who still fall under CLIA. And I'm not sure what we can do about that. But it does seem to me that we need to provide either more guidance, more explanation, more support, or demand of them more qualifications and more experience. And I've heard people say, what about proficiency testing for point-of-care testing? So anyway, I'll stop there. Over. CLIAC CHAIR: Thank you. CLIAC MEMBER: So in listening to all of the conversation here and [CLIAC DFO] comments on the simplicity of antigen test-- a card, or paper, as we've been using for decades to verify if someone has malaria-- the simplicity and the cost are critical to people using tests today. I think it's time that this committee discusses the possibility of coming up with some standards that will be starting now, and then going forward, especially for the COVID testing. But I think it's time that we think about what [FDA EX OFFICIO] mentioned. When you hear the progress they made in Korea-- not to say that we don't want to keep everything open, because we need the more tests that are-- the more tests, the better. But it sounds like the more tests are not better. It sounds like, if we have the ability to have standardized tests for this certain pandemic, then it would be easier for those waived tests to be used by people who are just using them for the first time. So, I'd like to take the discussion and the recommendation to another idea. And that is recommending standards specifically related to this pandemic and the testing going on now that we can then migrate over to other tests in the future. But that would be a direction I would recommend. CLIAC CHAIR: [CLIAC MEMBER], could you be a little bit more specific when you mean standards? CLIAC MEMBER: So today, as I'm hearing and participating in these conversations, there are so many tests available for so many different things that people make up in the labs, that they've been using them for decades, or they're brand new. So, to solve the problem we have right now-- and that is, we're getting inaccurate tests. We're getting things that are not really measurable, because there's always a question. Isn't it time to come up with some standard tests specifically for COVID that we can find a way to mass produce at certain locations, because here's the recipe of how to make it? Why don't we come up with some standards for CLIA so that the FDA can spend more time making sure the standard tests are working and that we're scaling up and scaling down with fewer tests. It just sounds so much more productive. CLIAC CHAIR: Thank you. CLIAC MEMBER: OK. Yes. I just wanted to say that's a very interesting topic and idea. We always deal with sensitivity and specificity. And sensitivity is better when there are fewer false negatives. And specificity is better when there are fewer false positives. So, although the formula's-- I'm going to try to address it-- I guess a percentage of true negatives and false negatives, how many are actually true negatives? Anyway, we've been focusing on false positives. And we have not really talked much about the false negative rate that was encountered in some of those over-the-counter and POC tests. And there is yet another way of looking at test results, which is the receiver-operator curve, which is with specificity versus sensitivity. And it's best when it approaches the value of one. And I tend to agree with [CLIAC MEMBER] that

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some of these concepts are difficult to explain, although I did see a very, very good New York Times article about what positive predictive value means. And I think it might be possible to have something-- some kind of insert, or link, or any of those things-- that people could access that said, what's the receiver operator for, and what's the ROC for your test that you're having? And these tests with low sensitivities I really don't think meet standards. I think the standard should be in the arena of an ROC as opposed to just the specificity or just a false positive rate. I really think we need to address the false negative rate. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, this is something-- again, as an OB/GYN geneticist, we're doing screening all the time. Marc is 100% right. It is not even worth going there to start talking about TPBs and MTBs. What doctors need and the patients need is really, what do I do next? There are actually two issues. One is what we are hearing is that, when you have the-- is actually just collecting these tests properly, just sample collection. So that's one issue. And then, what you do next? But they both have to do with education. They really do. And again, there are a lot of other areas in medicine-- in life in general, but in medicine-- where there's usually some very good educational tools. If we don't have the people using these tests educated and also-- again, for example, in genetics, we use these act sheets-- they're trying to get them digitized now-- where it really tells you what you do when you have a certain finding. Again, it comes back to communication. It comes back to how we educate. But we don't have the person power right now to do all the counseling. And I really feel strongly even getting into a discussion of a TPB or an MTB is not going to be helpful. That's really something that you understand from screening. But it is just very difficult and doesn't even necessarily help. People just want to know what they need to do. So again, I'd love to see a real effort-- and it's been mentioned, if we don't ask for it now, this is not going to show up a few years from now. And we've seen in the FDA there are great products that aren't used appropriately. There have been devices that can be lifesaving and, if you don't use it the right way, can cause real harm. So, I'm just advocating that what I feel like I'm hearing is really an educational deficit that we maybe can ask for resources to address and use some of the tools that are out there. CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I'm going to butt in before [CLIAC MEMBER]. And I just want to try out for thought-- we talked about waived testing. And the original definition was so simple to do, you can't do it wrong. But the risk of harm is low if you did it wrong, or over-the-counter testing. The example that [CLIAC MEMBER] presented of the two antigen point-of-care tests and [CLIAC MEMBER] desire for standardization-- is that unique to the EUA era where a point-of-care test became synonymous with waived? Would we not have seen that issue when we are not in an EUA? And then, in terms of proficiency testing, I'll just comment that the College of American Pathologists does not recognize the category of waived. And so, if you offer a test and you offer multiple methodology, some of which might be waived, you end up doing comparison testing. In California, that's twice a year. You just got to be careful you don't get accused of PT when you're doing this comparison. So [CLIAC MEMBER], I'm going to toss it back to you. CLIAC MEMBER OK. And I'm really interested in a lot of things that [CLIAC MEMBER] is thinking about from a patient advocate point of view about patient access to testing, and then building upon what [CLIAC MEMBER] said about telling patients what to do next, and then my concern over a reasonable amount of false positives. But to me, I consider 30% false negative to be unreasonable. But by repeating the test—So, if you repeated, you could have a couple of possible education rules. One is, if you have a false negative, repeat it at least two more times. If you have a single false positive, contact your physician. The other alternative would be to say, if you have a false positive and no symptoms, reduce your contacts and test again. And you'd have to run through the math of where you feel you would get a certain percentage comfort level that you have a true positive versus a true negative. And I know, at one point, I think it was [FDA EX OFFICIO] was talking about repeated testing as a means of improving the sensitivity. CLIAC MEMBER: That's right. CLIAC CHAIR: So, time check, we have 19 minutes on the schedule. Some of the proposals that are coming through the chat box-- two from [CLIAC MEMBER], and one from [CLIAC MEMBER] -- are being put on the screen. And I throw it out to the group, is there something we want to move forward? While we're thinking about it, [CLIAC MEMBER], you have another comment. CLIAC MEMBER: So, this has to do with making a motion that would answer a couple of these questions. And one of them would be to make a recommendation to fund at-home self-testing, and then also fund the training of the implementation. And so that would be the simplicity of-- many of us are familiar with on boarding now when you get new jobs. Many of us are used to doing things ourselves. So if we could make a recommendation during this pandemic to help add another tool to the tool chest of preventative spread, include this in the funding that we just received, and include the education and management of this self-test, and put the urgency on it right now-- we need to do what other countries are doing. And that is provide all people with the capability of preventing the spread through these kinds of self-testing tools at home.

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CLIAC MEMBER: Yeah. And just to come back to point-- and certainly testing training, education-- I do think that there are some opportunities to try to explain the odds of you actually having the disease if you tested negative. If you were going to Vegas, this is your chance of a payout. I think there are some ways of describing it that people might be able to understand. Obviously, predictive value is not one of those terms that's going to translate well. But if I understood correctly, I think that's under the purview of the FDA. So, there may not be much that we actually can do here. But I don't want to lose sight of-- and I think [CLIAC DFO] made this point-- the waived testing that's being done in health care facilities. And I would also like to make a recommendation that oversight for the care/waived testing in health care settings be tracked and appropriate oversight be developed. CLIAC CHAIR: Thank you. The lineup is [CLIAC MEMBERS]. And [CLIAC MEMBER] is busy chatting in the box that Heather is adding to the screen. CLIAC MEMBER: So, I'm looking at a news item dated March 12, 2020. Representative Katie Porter gets the CDC chief to agree to pay for coronaviruses testing. And I don't know if you all remember that. But that— CLIAC MEMBER: I remember. CLIAC MEMBER: Yes. OK. So, it was Redfield? CLIAC MEMBER: Yep. CLIAC MEMBER: So, you said, in the setting of a pandemic, the CDC will cover the cost for testing. I don't know if anybody ever put aside the funds for that. But that's on record. And she referred to the rule in the register that allows the CDC director to say that. CLIAC MEMBER: Well, and our new President also said the same thing, as far as being able to test yourselves like a birth control test. CLIAC MEMBER: Right. Now, to really get the kind of accuracy that we're talking about, we're talking about triple the cost, because you'd repeat it three times. CLIAC MEMBER: No. What we're talking about is antigen fast tests. Today, I can get 100 UTI fast tests from Amazon for $6. CLIAC MEMBER: But how accurate are they? CLIAC MEMBER: These? Let's talk to [FDA EX OFFICIO]. We know that there was just results that were put out from-- I'm not sure what University it was. But they did a huge study on rapid tests with antigen tests and the positivity rate. And the reality was, the more testing, the better. CLIAC MEMBER: Right. Right. CLIAC MEMBER: And so, these are inexpensive paper tests. What I would say, at this point, we need to curtail the spread. CLIAC MEMBER: So, I would say-- I mean, I contend, throughout a $5 value for testing— CLIAC MEMBER: It's less. It's less than $1 to make these tests. CLIAC MEMBER: For UTIs, or for the-- I don't know what it is for the COVID test. CLIAC MEMBER: You know what? On mass production, it would be next to nothing for these tests. I mean, we don't-- we're talking about a screening process to screen for it. CLIAC MEMBER: And I'm agreeing with you. I'm just saying, the funds are there, or the funds could be there? Then— CLIAC MEMBER: Oh, yeah, they're-- the funds— CLIAC MEMBER: Maybe there's some—

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[INTERPOSING VOICES] CLIAC MEMBER: The funds are there right now. --to put that in place. CLIAC MEMBER: In the most recent legislation that came through, the funds are there for that. CLIAC MEMBER: But one is putting it in place. And then number two is, what are the next steps? I mean, I live in Texas, which has dropped all mandates for masking, et cetera. CLIAC MEMBER: That's why this needs to be federal. CLIAC MEMBER: Yes. There needs to be a federal guideline as to what you do next based on your symptoms. CLIAC MEMBER: Yeah. Yeah. CLIAC MEMBER: And there's— CLIAC CHAIR: Let's focus on-- the issue was, can we distribute this widely for home testing, and ideally at no cost to the user? CLIAC MEMBER: And I would say, based on Katie Porter's conversation with Redfield, yes. CLIAC CHAIR: So that could be a recommendation from the committee. There is a draft recommendation from [CLIAC MEMBER] to that point. [CLIAC MEMBER], you had a number of comments to make? CLIAC MEMBER: I don't know if it's a number. There may be some merit in doing that. I've already stated some concerns about ad-hoc and ad-lib testing for screening at home. I think-- at least from my personal perspective, and probably from a public health perspective-- if that were to be employed, I think there's a lot more that needs to be known besides quote, unquote, "funding home testing." I think I would need to be compliance with a professionally designed testing program. That would be really helpful to people, so they would know what to do with their results. We need to involve national and state public health. There's a number of issues in what scenarios to use. How do you access the devices? What is it? How are they distributed? Who are the vendors? How are the vendors going to make it? What is the ideal frequency of testing? How is it reported? What are the scenarios you use it in-- family context, workplace-- to avoid adverse results application? How do you apply the results to your life? And how much testing is enough? I think there's a lot that needs to be answered. I think, if the entire program could be scenariolized in a scientifically useful way, it might be something to consider. But I don't think it could just be at the discretion of whoever feels like they want to do it that is a-- I don't mean to be deprecating but is a non-health care professional. Thank you. CLIAC CHAIR: Thank you. My sense is we still are discussing. We have not seemed to coalesce around key recommendations. And I would like to know, is there enough that we need to create a committee to carry this further, the discussion? And when I say that, I'm hearing the urgency in many of your voices that we cannot wait. And creating a committee introduces lag. I would say there is also prior discussions on waived testing, on point-of-care testing in previous iterations where we have addressed many of these issues. So, is there something new to this particular era that we want to put a recommendation forward? And the one that is shining through to me is the distribution of home testing supplies at no cost to the user. All of the other issues around interpretation-- AI tools, instructions, education-- are all part of what we've debated previously around waived testing. Is there discussion around moving forward a single recommendation? [CLIAC MEMBER] has asked, can we demand a committee to be formed within 30 days? CLIAC MEMBER: I guess my comment would be in support of [CLIAC MEMBER] recommendation in terms of increasing the training and education of our existing tools and dispersal of those. The companies-- I read all of the product inserts. I'm not sure my 85-year-old mother could manage that herself. I think that that's something simple that could be attacked without a committee-- that we focus on the existing methods that are already approved, and make the manufacturers improve the pre-analytic, the analytic, and the post-analytic instructions. I've given multiple webinars to nursing homes trying to use the Binax antigen. Yes, it's simple for laboratory phlebotomists, lab assistants. But you would not believe the things that came up in the training with health care professionals, let alone the lay public. So, I think that's a worthwhile initiative. Whether that's in the bounds of our committee as CLIAC, I don't know exactly. But since they are FDA cleared for home testing and such-- I mean, that seems like it would be-- but I would like to see that moved quickly, because people need it. And then we could form other committees about general point of care, and risk stratification, and other things down the road. But we have to get people to understand this better. And the tri-agencies have people that could convert these and improve these product inserts to the point where it would be available, and perhaps recommending calling a doctor, or your provider, or something much more strongly in those package inserts.

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CLIAC CHAIR: Thank you, [CLIAC MEMBER]. I want to comment. I trained my lab staff by having them watch the videos that the manufacturers had on their websites as a circuit way of teaching. Comments from [CLIAC MEMBERS]. And I believe we are seven minutes left in this, and I'm not sensing we have a conclusion. CLIAC MEMBER: I am talking. I'm on mute. Yes, I just want to say I am actually also supportive of getting these tests, and also that they really should be at no cost. The issue-- it's coming back to the same thing again-- is, can we put in some language? I don't know if we can have the FDA ensure that the inserts make sense, or if we can add on a recommendation that we need to focus on the teaching and education surrounding the use of these products and see if we can get some resources for this now, but that should really be a focus, and not just getting the test out there, because we just had-- most of the discussion was our concern if you don't have the educational piece. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yeah, just very briefly supporting [CLIAC MEMBER] concern. There was a study quite a few years ago in [INAUDIBLE], and I believe France, on a point-of-care pregnancy test with spiked specimens involving quite a large number of women. And 99% of the women said the test was easy to use. And 50% of them got the wrong answer. So, I think that pre-analytic and post-analytic are very important. And maybe that's something that could be done quickly. That's all. Thank you. CLIAC CHAIR: Thank you. CLIAC MEMBER: So, I think we need to be also very sensitive to the fact that this at-home self-test does not need to be complex and expensive. We need to make sure that it is available to all and that our nation doesn't go broke providing this for everyone. So somehow, in this recommendation to fund at-home self-testing, it needs to be reliable, and low cost, and-- reliable and low cost to our nation, that we're not getting with vendors that are going to charge $5 when it takes about $0.50 to make. So, we need to make sure that this is something that can be repeated, and it's low cost, affordable for our nation, but it has the results. And that was the recommendation-- to fund reliable, low cost at--home self-testing and training, education for location of testing. And I— CLIAC CHAIR: You froze. CLIAC MEMBER: Yeah, I've just been-- I'm watching what she's doing, because I'm going to make a motion to approve what she's just written. And I think she's done. Yeah. So, I'm going to make a motion to pass this recommendation to fund reliable, low-cost, at-home self-testing and the training and education for the implementation of this testing. And funding would need to include result reporting to the cloud for public health practice. CLIAC CHAIR: So, there's a motion on the table. Is there a second? CLIAC MEMBER: I will second it. CLIAC CHAIR: Thank you. Now there is time for discussion. But I want to comment. [CLIAC DFO], and then [CLIAC MEMBERS] are in the wanting to make comments. We'll start with [CLIAC DFO]. CLIAC DFO: So just in the interest of having some recommendations that the agencies can work on and implement in the near term, CDC does have responsibility to support education and training and outreach to the laboratory community, which includes the point-of-testing testing community. And under COVID at least, it's also including the at-home testing community. So a specific recommendation for CDC to advance training and education materials for this type of testing we could act on fairly quickly in a way that it will be hard for us-- these three agencies right now, given our responsibilities-- to immediately act on finding funds, even though the funds are there somewhere. Over. CLIAC CHAIR: Thank you. CLIAC MEMBER: So something educational could be as simple as, when you pick up the kit at the pharmacy, or store, or whatever, that you have to go watch a video on how to perform it, and that you also-- and that's presuming that you don't have any access to internet, TV, et cetera in your home. So, you watch the video where you get it. But you can also be given a link so that, if you do have access to internet, et cetera, you can watch this video again and again. And it's one thing to read and show pictures. But it's another thing to watch a person actually do it and try to do that to yourself then. CLIAC CHAIR: Thank you. CLIAC MEMBER: I think that might be too specific.

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CLIAC MEMBER: Yeah. I would just wonder if we're going to do this today or whether there should be a committee. I am curious to know-- and I do not know. Perhaps those on the call do. Are there any peer-reviewed public health or other academic literature that is purporting this to be effective and an efficient way to [INAUDIBLE] population intervention for COVID? I'm just wondering what's out there. Well it seems like a good idea, fine. But I'm just curious if anyone's ever looked at it in a systematic and peer-reviewed fashion. Thank you. CLIAC CHAIR: I thought [FDA EX OFFICIO] had mentioned some trials going on in North Carolina, which were trying to look at this. FDA EX OFFICIO: Yeah, this is a challenging area. And I think it would benefit from well-designed studies. It's not just, will people use it, and will they behave in the appropriate manners? But will we actually make an impact on community spread? There were some efforts in Europe. But they are not necessarily designed in a way that would completely function in the US. And so far, the results in Europe are mixed. I really think that it's probably a good thing to do. But actually, showing that it works is a bit challenging. And one thing-- the programs in Europe have a key. That is, if you test positive, you must quarantine for a certain period of time. And you will be monitored. And if you break the rules, you get a heavy fine. And I don't know that those-- And some of it sometimes, in some of these countries, is enforced by the police and the military. So, I don't know that it's completely translatable. But NIH, Francis Collins, has funded a large community study. And we will know, hopefully in a matter of weeks, if it can to be deployed in this manner in the US, and perhaps what other guardrails we put around the testing in order to make sure that it's effective. CLIAC CHAIR: Thank you. Before, [CLIAC MEMBER], I call on you, [CLIAC MEMBER] has asked that-- in your proposal that's on the open motion, in that second sentence, the implementation of this testing, could we clarify what this testing refers to? Is it just SARS-CoV-2? Or is it bigger than that? CLIAC MEMBER: Right now, we just need to address COVID-19. CLIAC CHAIR: So, of SARS-CoV-2. So, we have that motion. We have a second one underneath, which we've not yet opened. So, do we have enough discussion? [CLIAC MEMBER] has withdrawn his original question to comment. Do we have enough discussion that I'm ready to call a vote on the open motion? Is there anyone else who would like to speak to us? CLIAC MEMBER: I'm thinking we just need to separate the financial funding thing from the education one, and take that, and split it into two recommendations-- one for training and education, one for the funding of that-- because I understand that that might be two separate things. Is that right? CLIAC CHAIR: I think so. So, [CLIAC MEMBER], your revision would be recommendation to implement reliable low or no cost at-home self-testing. Is that what you're driving at? CLIAC MEMBER: No, I'm suggesting to take the, including training and education— CLIAC CHAIR: I see. CLIAC MEMBER: --out of that and put it down with the CDC one, because that's basically an overlap. CLIAC CHAIR: Yes. So, the statement has been amended, recommendation to find reliable low-cost at-home self-testing for SARS-CoV-2. Funding would need to include results reporting to the-- I would just move, to the cloud. We shouldn't prescribe how that reporting occurs. CLIAC MEMBER: Correct. Then, that way, that first one is additional funding. And we might want to even string that together because, let's face it, there is at-home testing now, some of which is maybe more expensive than we would like. So, we can keep the low cost in there. Some things exist. But nothing, to my knowledge, is still open, is still automatically reporting like a diabetes test would, or to public health. So that's, I think-- that's tied together. But it's separate from the education for the existing. For any existing ones, they can start right now with enhancing the education and training. For future ones, that would just follow if there's new methods approved by the FDA, I would think. But I think the focus on making them easier for at-home and for point-of-care providers is-- I mean, I know we're talking about at-home testing here. But the truth is we don't really have the master solution for the nursing homes and long-term care facilities either. CLIAC MEMBER: And this would work there, too. CLIAC CHAIR: So, I would wordsmith this a little further-- recommendation to fund reliable, low-cost, at-home SARS-CoV-2 self-testing and interpretation, comma. And delete, funding would need. And then finish with, to include results reported.

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CLIAC EXECUTIVE SECRETARY: Can I ask you a question for clarification on this one? Who are you recommending this to? CLIAC MEMBER: For the public. Recommendation— CLIAC EXECUTIVE SECRETARY: I know. But who are you recommending fund this? Because this committee is charged with making recommendations to the Secretary for HHS or to the three agencies that are part of the CLIA program. And again, CLIA does not cover self-testing. CLIAC MEMBER: We are making a recommendation to the administration through HHS. CLIAC DFO: I think all you can say is that, recommends that the HHS Secretary. Unfortunately, this committee is not empowered to make a recommendation directly to the White House. CLIAC MEMBER: Right. But do it through HHS. REYNOLDS SALERNO: No. But all we can do is make a recommendation to the HHS Secretary. CLIAC MEMBER: Right. Right. CLIAC DFO: The HHS Secretary gets to do with this whatever he or she chooses. CLIAC MEMBER: That's right. CLIAC CHAIR: I'm sitting here thinking, do we want the war funding there? Do we want it instead? CLIAC recommends the HHS Secretary make widely available reliable low or no-cost. CLIAC MEMBER: I think that that doesn't cover what we talked about, and that is no cost to the public. CLIAC MEMBER: I'm concerned, the way it reads now, that HHS will be funding that. CLIAC MEMBER: That's what it says. CLIAC MEMBER: Can we say, to explore funding, or to investigate funding, or something like that? CLIAC DFO: Make widely available low-cost testing. CLIAC MEMBER: Then that means people have to pay for it. CLIAC CHAIR: Well, we could say low— CLIAC DFO: Low or no cost. CLIAC CHAIR: --or no cost. CLIAC MEMBER: And why can't we go back to Redfield's comment that the CDC can and would cover the cost? CLIAC MEMBER: Well, he's not in anymore, so there's that. CLIAC CHAIR: Yeah. So, is this-- is there any further modifications? [CLIAC MEMBER], did I cut you off? CLIAC MEMBER: So that looks like a —That looks like that's a good recommendation. CLIAC DFO: I was just going to say, on the education and training one, I thought I heard-- but maybe I was wrong-- that it would be for self-testing as well as point-of-care testing. CLIAC MEMBER: Yeah. CLIAC CHAIR: But we don't have that open yet as a motion, guys. Come on. Let's focus. We'll get there.

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CLIAC MEMBER: Well, you could really take these two home test motions and just plug in point-of-care so we have four motions coming out. But— CLIAC CHAIR: So, let's start with our open motion. Are we through word smithing now? CLIAC MEMBER: Do we-- I know there's self-testing and interpretation with access to care. I mean, do we want to say something-- to me, that says, I'm going to test myself. And I'm going to interpret my test. I'm going to report it to public health tracking. But what am I going to do about my positive test? And I know some of the HIV— CLIAC MEMBER: So that was going to be the education, right? CLIAC MEMBER: Education, OK, for SARS self-testing and point-of-care-- self-testing and self-referral for care. CLIAC MEMBER: Yeah. CLIAC CHAIR: Can we be-- because then we're touching on clinical care and our clinician counterparts, who are not in this conversation, outside of [CLIAC MEMBER]. Can we ask that that follow-up action be included in the educational material? CLIAC MEMBER: Yeah. CLIAC CHAIR: OK. So first we have the open motion on the floor in yellow. And I would like to call the vote. Are there any opposed? Four are opposed. Are there any abstentions? CLIAC MEMBER: This is [CLIAC MEMBER]. I'm not sure how to vote. But I think I would be opposed as well as written. CLIAC CHAIR: I abstain. So, let's do the head count on-- oh, [CLIAC MEMBER], did you raise your hand? CLIAC MEMBER: I'm going to abstain as well. CLIAC CHAIR: OK. [2 CLIAC MEMBERS] abstain. Did someone else speak up? I'm sorry. CLIAC MEMBER: Yeah. I think I would abstain as well because I'm not quite sure which way I vote . CLIAC CHAIR: OK, so if my math is correct, four oppose, three abstain-- seven. That still allows a majority vote, correct, because there are 20 of us? Are there still 20 of us on the screen? OK. So, I'm going to actually ask that we do the roll call. And if somebody could help me scribe-- and I'm just going to go by the tiles I see. CLIAC MEMBER: Is there an option for hearing the opposition? Can we fix it? Or is it-- since there's so many people undecided, it seems like maybe we just need to— CLIAC CHAIR: Yeah. I think, [CLIAC MEMBER], I agree with you. CLIAC MEMBER: Or that's not the way it goes. CLIAC CHAIR: If they're-- well, if there's at least seven people who are not ready to sign on, it means to me the issue is too complicated with all the conversation we had earlier. And maybe the route has to be a committee. CLIAC MEMBER: Me, too. CLIAC MEMBER: Can we just take a moment now and see if some people would like some tweaking of this that may change their direction? CLIAC DFO: I have a-- I could do a roll call, if you want, if you want to get the actual vote. It's up to you, [CLIAC CHAIR]. CLIAC CHAIR: Yes, please, because I actually don't think, with all due respect, we have enough time to understand folks' perspectives on why they voted. So please, [CLIAC DFO]. Thank you. CLIAC DFO: OK. [CLIAC EXECUTIVE SECRETARY] or Heather, can you keep track while I call names, keep track of votes please? CLIAC DFO: OK. Thanks. And apologies, I'm going to use first names just to go more quickly.

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[A ROLL CALL WAS TAKEN TO VOTE ON THE PROPOSED RECOMMENDATION. TEN MEMBERS VOTED TO APPROVE, FIVE MEMBERS VOTED NOT TO APPROVE, FOUR MEMBERS ABSTAINED, AND ONE MEMBER DID NOT VOTE] CLIAC CHAIR: My tally is 10 yes, four abstain, five no. So, it's basically 10 and 9. It is 5:44. This meeting is scheduled to end in 16 minutes. Is that adequate for a majority vote? Donna said, when we're split like this, it seems maybe we should talk about it some more to understand. CLIAC MEMBER: Can we try one more time for [CLIAC MEMBER]? Because depending on his vote, there may or may not be a majority. CLIAC DFO: Yeah, we don't have a majority. We need 11 to have a majority of the members. CLIAC CHAIR: Who would have thought [CLIAC MEMBER] vote would be so important? CLIAC MEMBER: What about we wait for him to come back and work on-- and see if we can get to consensus on the CDC education and training one? CLIAC CHAIR: Yeah. So, I actually think the second sentence is very straightforward. Before we do that, and for our public members, we do have 15 minutes left in this meeting. I would ask that you indulge us. I hope we can wrap this up by 6:15 your time, so an extra 15 minutes. So I'm going to do what Robert's Rule says you're never supposed to do, which is move this open thing off to the side while I'll entertain a motion to approve the second sentence, CDC should develop and training and educational materials for SARS-CoV-2 self-testing and point-of-care testing. I will make that motion. Is there a second? CLIAC MEMBER: Second. CLIAC MEMBER: I'll second. CLIAC CHAIR: Multiple seconds. Thank you. Is there a discussion? CLIAC MEMBER: I have a question. CLIAC CHAIR: Yes. CLIAC MEMBER: I think we should call the question in the interest of time. CLIAC CHAIR: Thank you. I actually think this is relatively non-controversial. CLIAC MEMBER: I know. That's why I said that. CLIAC CHAIR: So, I was waiting my seven seconds of silence. But you came in second— CLIAC MEMBER: I just wondered if we wanted to add, self-testing, comma-- self-testing, and point-of-care testing, and self-referral. CLIAC CHAIR: Oh, yeah. So, it's actually, self-testing, and point-of-care testing, comma, and follow-up care. CLIAC MEMBER: Yes. And follow-up care. Yes. CLIAC MEMBER: Sign the amendment. CLIAC CHAIR: OK. Is there any other discussion? OK. I would like to call the vote on this. If we could do the roll call again-- it takes three of us to do a roll call. [CLIAC DFO], would you kindly call the names? CLIAC DFO: Do you think we need to? I mean— CLIAC CHAIR: Oh, OK. CLIAC DFO: Is there opposition?

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CLIAC CHAIR: Does anyone oppose? CLIAC MEMBER: No. CLIAC CHAIR: Does anyone abstain? So, this one passes by unanimous vote. And [CLIAC MEMBER] has not responded despite Nirali pinging him. So, let us have a— CLIAC MEMBER: So, [CLIAC MEMBER] -- was it [CLIAC MEMBER] that said he’s open to discussing? There was someone who said that.

Future CLIAC Topic Discussion CLIAC CHAIR: Yeah. So, before we do that, I would like to go to this other final agenda item, which is to solicit ideas for some of the committee members around future CLIAC topic discussions. So, who wants to talk about what? CLIAC MEMBER: I have a quick question. [CLIAC CHAIR], you had a recommendation right before lunch. Are we going to vote on that recommendation? CLIAC CHAIR: Our half-baked recommendation? CLIAC MEMBER: Or is that going to cook? CLIAC CHAIR: No, we don't. That's not ready yet. So, it's not ready yet. We're going to leave it in the oven and probably come back to it. CLIAC MEMBER: Can we bring it back for upcoming, just to tie together the end of this meeting? Is that something we can talk about in the next upcoming? CLIAC CHAIR: So that recommendation is coming out of the need for a rapid surge capacity and scale-up relative to a pandemic. We could consider for the next meeting. I personally see we're in a race with the vaccine and that, at some point, testing will become not an issue. I mean, we'll still need to test, but not with the urgency perhaps, if we're fortunate. CLIAC MEMBER: As they say, from your mouth, to god's ear. We hope that's-- CLIAC CHAIR: And even now, we're just learning around breakthroughs. So, I'm nervous about that statement. But since we cannot get resolution in this meeting, we will think about it for future meetings. But it will not come out of this meeting as a recommendation. I would like to throw out-- and it's been percolating, but I don't have a good suggestion-- to have a little bit of discussion of the role of CBER versus FDA diagnostic devices, the relationship of that with transfusion medicine and blood bank testing at the core. And that is because many of the blood bank test systems now are classified as moderate complexity, unless they're used for transfusion. And that leaves the clinical lab in the awkward position of trying to understand if a test is going to be used for transfusion purposes. CLIAC MEMBER: And we could also discuss the scope of Certificate of Waiver relative to blood product testing. CLIAC CHAIR: Ooh, yeah. So, we could have this blood bank thing. And then I lobbed this at [CLIAC MEMBER] a couple meetings ago around the CLIA personal requirements. And the immunohematology technical supervisor does not exist in CLIA. And we have a number of SBBs who are superb and yet, by CLIA, are not recognized to be allowed to perform that function. So, I'll lob that out as a topic. CLIAC MEMBER: Scope and practice for SBBs. CLIAC CHAIR: Yes. [CLIAC MEMBERS]. CLIAC MEMBER: Yeah. I'd like to discuss further how sequencing can be part of a CLIA approval process so that you can validate CLIA practices. CLIAC CHAIR: Thank you. And then maybe that can relate to the work group on next-generation sequencing, the prior being [INAUDIBLE].

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CLIAC MEMBER: I think we've discussed this before. But I think, [CLIAC DFO], exclamation point today on health information exchange. I think we need to help the CDC get what they need. That will also help CMS and the FDA by having the seamless exchange of test results. I think this needs to be a priority, since it's obviously something that would have solved lots of problems for this pandemic. CLIAC MEMBER: Yes. And I don't think we're going to have time to wrap up quality and what we do about the quality of waived/point-of-care testing. There's a recommendation on the table that we just don't have time to discuss. So perhaps we could kick that to the next meeting? CLIAC MEMBER: I think we should try to talk about that if we could. I mean, it is an urgent need. If there's some discussion we can have with those people that were kind of on the edge, could we use five minutes to do that? CLIAC MEMBER: I'm talking about the recommendation that I made, [CLIAC MEMBER], about increased oversight of point-of-care in the health care setting. CLIAC MEMBER: Oh, OK. CLIAC CHAIR: And [CLIAC MEMBER], I'm going to ask you to make your comment. CLIAC MEMBER: OK. I'm happy to. I think we touched on it before. But I think we may want to return to a discussion, a deeper discussion on the role of the laboratory in addressing health disparities. It's certainly become increasingly more of an issue in the last year. But it always was. CLIAC CHAIR: And I would say it directly relates to what we were talking about where we could not get agreement on this motion, that the community's less advantaged are definitely disfavored in COVID testing. CLIAC MEMBER: Right. It's a build on my original-- my first day back on the CLIAC, I said, I think we should address social determinants. This may be a little bit more focused. CLIAC CHAIR: Are there other considerations? CLIAC MEMBER: So, are we talking about bringing [CLIAC MEMBER] motion back up for discussion? CLIAC CHAIR: As soon as we have accumulated all of our comments. CLIAC MEMBER: Comment on it? Because I would like to make a comment. I was just looking at some publications— CLIAC CHAIR: I'm sorry. No. CLIAC CHAIR: I'm -- very concrete. Are there any other considerations for future topics? CLIAC MEMBER: Oh, OK. CLIAC CHAIR: Yeah. We're almost there. I'm counting the seconds. Seven seconds of silence have passed. I have not heard any more comments. So, we will close this discussion about potential topics for future meetings. Now we can get back. And Heather if you could project where we were with that statement. And [CLIAC MEMBER], go for it. CLIAC MEMBER: So, I have been one of the people who has been most vocal about the false negative rates. And I actually looked up a couple of peer review papers while we were sitting here. And what's interesting is-- and it makes sense-- that the false negative rate goes down in symptomatic patients and goes down maybe not quite as much in asymptomatic patients. So that says to me that, although this might not be a perfect way of saying whether you are gold-standard negative, one would presume that how much antigen you have may have something to do with how infectious you are. And that may have something to do with how symptomatic you are. Not to say that asymptomatic people aren't always infectious, but those that don't test may not be infectious. So I may be making a presumption here, or an assumption that those are related, and that if they are related in the way I think they are, then the tests would be useful in alerting people even if infected, but having low infectious capacity. The people that it wouldn't alert would be people who have low infectious capacity compared to those who have high infectious capacity. And that would be very useful, even in the face of some of these issues of false negatives. CLIAC CHAIR: So, during the evolution of last year and this antigen testing, the guidelines continue to evolve such that, if you initially tested positive by whatever test, 14-day quarantine. And then it moved back to 10 days. And then, if you were-

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- the issue of antigen negative, the discrepant thing, antigen negative, nucleic acid positive. What was the quarantine rate? It would be less than 10 days or 14 days. Some of this is backed with the instructions. And then, why would you even be testing after 14 days of symptom onset? All of those factor into when you want to do a test. I am coming back to, is there any way this statement can be altered by the four abstainers and the five opposed such that, in the next 15 minutes, it would be acceptable? So, I'm calling on the nine. And [CLIAC MEMBER] is MIA. Oh, I'm sorry. [CLIAC MEMBER] has a comment. And then [CLIAC MEMBER] has a comment. CLIAC MEMBER: Yeah. So, I went back to look at our data, because we ran several pods and several bubbles. And now, re-looking at the data, the antigen now says, did not perform very well at all, considerably below what the package insert indicated. So, I'm not even sure there is a reliable-- it depends what the word reliable means. And so, I'm having concerns now about what I was thinking about this before. CLIAC CHAIR: And I believe you voted yes. Correct? CLIAC MEMBER: Yeah. CLIAC CHAIR: OK. CLIAC MEMBER: OK. Hey, thanks. No. My thinking is that the open-ended provision of home test without more guidance or evidence of testing effectiveness on disease is an uncontrolled public health policy. I'm not opposed to the idea. But absence more thought-- and, ideally, research-- I think this is premature at this time. It might be a good idea. And again, I've not researched this at length. But I think that this is a bold proposal and could include a significant amount of funding. It looks pretty open ended. We don't know how the tests will be used. And I'm not sure it's a bad idea. I just think it really needs more thought, respectfully. Thank you. CLIAC MEMBER: I'm with [CLIAC MEMBER]. I think it needs more thought and needs to have more data. This needs to be a data-driven decision. There's too much work involved in this and money involved in this not to have data. And the results I have seen of antigen testing-- say, schools, for example-- it is not a good indicator that this will be successful. CLIAC CHAIR: Thank you. [CLIAC MEMBER] has suggested adding a qualifying statement-- dependent on the results of active clinical trials. CLIAC MEMBER: As we were told, there is a trial underway in North Carolina and Tennessee. So, if those results do show that this is an efficacious approach to public health testing, then we would have that open-ended recommendation, if that would help address some concerns. CLIAC MEMBER: I'm on board with that. CLIAC MEMBER: And then the only thing I would say is, active clinical trials pertaining to the efficacy of a specific test. CLIAC MEMBER: Right. CLIAC MEMBER: The longer I deliberate upon it, I do have concerns about trying to force funding without, I guess, further debate and having a clear understanding of where that funding would really derive. And I guess maybe I would like to see us focus a little bit more around our recommendations around laboratory quality. And maybe we could parse out the portion recommending result reporting for public health tracking and separate that out as a separate recommendation, and then give a little bit more thought around a recommendation, and maybe a recommendation around recommending funding and availability of the testing, and maybe moving back to the group. I do think that testing is being made more available through the approval of various tests. So, I do think that that mechanism is already being acted upon, in a fashion, already. So maybe that would give us a little bit more time to deliberate, and give a little more thought, and maybe see how these trials play out. And maybe we can act a little bit more on that second piece. CLIAC CHAIR: Thank you. CLIAC MEMBER: Yeah. I agree with [CLIAC MEMBER] comment. I think my issue with the recommendation is really with the first part, which is the making widely available, reliable, low or no cost at-home-- I mean, we can throw unicorns in there. It just seems very nonspecific. And it seems just like we would be wanting-- we'd be advocating for costs to drive the reliability of a test, or something like that, as opposed to the best data. And I just have a problem with not really having a good-- it could have been a mask in there, as well. So, if we make all of this stuff available, how do we even ensure that anybody is going to be using it? How would we know that people would even adopt it, and that kind of stuff? So, I would

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hesitate to try to put funding towards that. I think, for purposes of our purview, actually constructing something for reporting to public health, for tracking, would be far more valuable. CLIAC CHAIR: [CLIAC MEMBERS] are in line. And then I would like to close the conversation after that. CLIAC MEMBER: OK. So, I just want to make a comment to say that, with these added changes, I agree with this caveat about, upon results of active clinical trials. And I just want to impress upon everyone the importance of understanding that there are people that are not being able to be tested. And they want to be tested, because if they don't have symptoms, they're being turned away. And that's been going on forever. Without symptoms, they don't get tests. That means they continue to spread, even though they were just around people who were infectious. I know everyone wants to make sure that there's plenty of information here. I can assure you that this has been the topic of discussion at the highest levels. Even [FDA EX OFFICIO] has talked about a priority for this. The only thing that's different is that it's actually being supported by our government, because that's what we need right now. So based on these additional changes, I would still like to move forward with the vote. And since it has the caveat of, upon results of the clinical trials, we are not going to get held up for six more months to be able to make those kind of recommendations. I urge you to think about the public and those who don't have access to this. There's many people that don't have tracking devices or access to the internet. They're homeless. And many more people that had homes before are losing their homes. So, we need to give them every tool they can to protect themselves, their families, patients. I mean, this is not a black-and-white discussion. It is urgent. Thank you. CLIAC CHAIR: Have I missed anyone? Folks are hopping off, as they have prior engagements at 6:00. [CLIAC MEMBER], you asked for another call of the vote. My sense of the conversation as it remains equally complex and detailed. CLIAC MEMBER OK. Can I make a recommendation that we have speakers that are experts to be able to participate in the next-- that are invited, to discuss with experts that will come and speak about this? CLIAC CHAIR: Yes. And I think that would fit nicely with [CLIAC MEMBER] recommendation to talk about equity and inclusion. So, given that this weighs heavy on our mind, we do not have a recommendation for this, with the exception of the single green highlighted statement. All of our other great ideas and discussion remain half baked, to be visited in the future. And with that, I want to announce our next meeting is November 3 and 4. Information-- I'm sorry, 2021. Information will be provided on the CLIAC website. And again, if you have suggestions for topics or suggested member candidates, send those suggestions to cliac@cdc.gov. Since we're having such a large exodus of such valuable members, I want to one more time recognize and acknowledge the help of doctors Couturier, Hinrichs, Laser-- although he was MIA-- Lorey, Perez, and Williams. And [CLIAC DFO] has his hand up. CLIAC DFO: Thanks, [CLIAC CHAIR] Yeah, I was going to say the exact same thing. I can't thank you enough and express enough appreciation for the six of you, who unfortunately are leaving our committee. But please know that we are extremely grateful for your commitment to CLIA, to CLIAC, to public health, as well as to equal access to testing across our country, and not just-- equal access to quality testing and reliable testing, which is I think really what we're all here to do. So, thank you so much to Marc, Steve, Jordan, Tom, Tom, and Katherine. And we really do hope to see you again in the future. We've had many CLIAC members return to CLIAC. And we need your expertise. And the other thing I'd like to do before we leave is to express appreciation to Heather Stang, who is probably more responsible than any of us for actually pulling off this meeting, coordinating with all of you, making sure that we all stay on track and stay within the rules and the laws of a federal advisory committee, which gets quite complicated. So, I really appreciate the work of Heather and many other people in our division who work behind the scenes to make this meeting happen. And we're really hopeful that the next meeting will be in person, although it may be hybrid, because I think, as some of you said yesterday, there's probably no reason to force these meetings to be all in person. But I think we do miss something. Maybe I'm old school, but I miss seeing many of you and all of you in person. And perhaps some of these exercises around creating recommendations would be easier in person than online. But regardless, we will meet in November, one way or the other. We'll let you know what format we will meet. But thanks, to everybody, for their commitment to CLIAC. We really appreciate it. And we really need your help to continue to get better at doing what we all do. So, thank you. Back to [CLIAC CHAIR]. CLIAC CHAIR: With that, what can I add? Meeting adjourned. Thank you.