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Biobanking in the Past, Present, and the Future:
Biobanking During COVID-19 Pandemic
Lyndsey Buckner Baiamonte, PhDSupervisor-Ochsner Biorepository Unit
April 14, 2020
OBJECTIVES
I. History of Biospecimen Collection
A. Henrietta Lacks
II. Importance of Biospecimens in Research
III. Establishment of Biobanks and Ethical Issues in Modern Day
A. Genomics Databases
B. Results Reporting
IV. International Standards and Best Practices
V. Ochsner Biorepository Unit Operations
A. Umbrella Protocol
B. Pathology Specimens
C. Leftover Specimens
VI. Biospecimen Considerations during COVID19 Pandemic
HISTORY OF USING CELLS FOR
RESEARCH
In 1850s-60s it was theorized by Virchow that diseases were caused by an alteration in human cells that cause pathology
Research focused on gross anatomy, physiology and bacteriology, using observational and culture techniques
Problems in conducting research to answer questions about:
• Virology
• Obligate intracellular bacteriology
• Cell biology
• Embryonic development
All require viable eukaryotic cells to study
Mouse L929 Cells
HISTORY OF TISSUE CULTURE
1858-1863- Virchow described cells arising from cells called “Cell Theory” and diseases as arising from alterations in cells
1885-First mammalian cell culture documented by Wilhelm Roux using embryonic chicken tissue in saline
1907- Tadpole spinal cord culture, documenting growth of nerve fibers by Harrison
1911- Chick connective tissue and heart tissue kept viable and passaged to keep growing using plasma as medium
1911- Discovery of a virus associated with cancer using tumor tissue from chicken (Rous Sarcoma Virus)
1940s- Antibiotics introduced into cell culture methods
1948- Establishment of first immortalized mouse fibroblast cell line “L-cells” by Earle
1951- Establishment of the first human cell line: HeLa from cervical cancer tissue of Henrietta Lacks by Gey
Rudolph Virchow
Rous Sarcoma Virus
(Reviewed in Hoffman 2016; Jedrzejczak-Silicka 2016; Weiss and Vogt 2011)
CONTROVERSY OVER HeLa CELL LINE
Henrietta Lacks was not asked or informed that her tissue might be used to create a cell line
• There were no regulations on informed consent or human subjects research in the 1950’s
• Henrietta Lacks was part of a vulnerable demographico Brings up questions on collection and use of her cells
o Even if approached for consent, presents questions about appropriate ways to approach vulnerable populations
Compensation for the family of Henrietta Lacks?
Ethical to use the data and research that resulted from her cells?
HeLa Cells
Henrietta Lacks
(Wilson 2016; Samuel 2017; Skloot 2010; Beskow 2016; Howard 1997)
MEDICAL DISCOVERIES MADE USING HeLa CELLS
Poliovirus growth and vaccine development by Jonas Salk
Discovery of p53 and retinoblastoma proteins targeted by human papillomavirus (HPV 18) E6 and E7 that causes cancer
Discovery of chromosome abnormalities in cancers and confirmation that humans have 23 chromosomes
Discovery of the enzyme telomerase and its role in cell aging, which aided in cancer research
Using transfection techniques, discovery that CD4 is the host cell binding protein for HIV
(Reviewed in Samuel 2017; osp.od.nih.gov)
IMPORTANCE OF BIOSPECIMENS FOR RESEARCH
Human biospecimens can be used to discover disease processes such as:
Alterations in normal cell pathways that cause disease
Biomarkers present in diseased patients that can be used for diagnosis
Novel pathogens causing disease
Sequence of COVID19 determined using specimens from infected patients
Genetic mutations in tumors and pathogens
Has led to targeted cancer therapies
Informs effective therapy options for patients
Has lead to the concept of precision medicine to treat individual patients
Has lead to understanding mutations of viruses, such as HIV and Influenza
THE PATHWAY TO A CLINICAL
TRIAL
ESTABLISHMENT OF HUMAN
BIOREPOSITORIES
The proactive collection and storage of biological specimens and data for research
Started in individual labs for specific projects
Recognition of a need for human specimens for researchers who cannot initiate collections themselves
The term ‘biobank’ was first used in the late 1990’s, as it was recognized that human specimens are incredibly valuable in research and should be collected and saved for these purposes
Biorepositories may collect and store: Tissues Biofluids Processed specimens: DNA/RNA/protein Data
(Cambon-Thompson et al 2007; Kaufmann et al. 2008;Hewit et al. 2011; De Souza and Greenspan 2013; Hewit et al. 2013)
INTERNATIONAL ESTABLISHMENT OF BIOREPOSITORIES
UCSF AIDS Specimen Bank
NCI US National Cancer Biobank Hub (caHUB)
University of the College of London biobanks
Population based biobanks in various countries:• Danish National Biobank
• UK Biobank
• Iceland
• Latvia
• Canada
• S. Korea
(De Souza and Greenspan 2013)
Genetic Data from UK Biobank
(EMBL-EBI Report 2017)
PROBLEMS IN THE BEGINNINGS OF
BIOBANKING
No standardization of ethical considerations when collecting • Genomics• Different countries have different regulations
No standardization for processing and storing• Variable cold ischemic times• Unknown practices for processing
Questions on reporting results• Should a patient be told of their results? Who should tell them?
No set projects for which specimens are collected• Specimens not ideal once projects developed• No consistency in collection • Many just banked specimens without thought as to how specimens
would be utilized
ESTABLISHMENT OF BEST
PRACTICES
Multiple publications discussed the need for high quality specimens with reliable data
In 2000, the International Society of Biological and Environmental Repositories (ISBER) was established
• Annual conferences where various parties meet to discuss evolving issues surrounding standardizing practices
• Publishes Best Practices for Repositories every few yearso Cost recovery as the best financial practice
o Facilities and equipment monitoring and maintenance
o Safety
o Quality Assurance and Control
o Ethics
o Specimen Processing
In 2005, The NCI established the Office of Biorepositories and Biospecimen Research (OBBR) and Biorepository Coordination Committee
• Published the First Generation Guidelines for NCI Funded Biorepositories• Now publishes the NCI Best Practices for Biospecimen Resources every few years• Initiated the Biorepositories and Biospecimen Research Branch of the Cancer
Diagnosis Program
(Biospecimens.cancer.gov; De Souza and Greenspan 2013, Picciochi et al. 2018)
LEGAL AND ETHICAL ISSUES IN
MODERN DAY BIOBANKING
Respecting the autonomy of human subjects
• True informed consent process with disclosure of all potential possibilities
Protecting subject from breach in privacy and confidentiality:
• HIPAA/Privacy Rule affects biospecimen collection even with de-identification practices implemented
• In recent years, increasing demands for specimens for genome wide association studies (GWAS)
o Public genome databases make genomic data ‘traceable’
• Issues with data sharing and privacy- “Big Data”
Minimizing harm to vulnerable groups
Providing results to subjects?
• Numerous discussions on whether there is an obligation to report results that can impact a patient’s health
o BRCA results, e.g.
Use of a Broad Consent
Like an Opt-out program
Does not allow for specimens to be used for specific things like genomic studies
Difficult to track in an EMR
(Biospecimens.cancer.gov; De Souza and Greenspan 2013, Picciochi et al. 2018)
Ochsner’s Biobank OperationsHow do we collect biospecimens for research?
PURPOSE We identify patients and collect, process, store, and ship valuable
biospecimens and data
Patients consent for specimens to be utilized for genomic, genetic, and biomarker studies, associated with disease or treatment efficacy (usually oncology studies)
We can provide these valuable specimens to researchers who are investigating parameters associated with positive or negative patient outcomes
Researchers may include:
• Internal investigators
• External collaborators, eg. UQ, LSU Shreveport, LSUHSC-NO, Tulane, etc.
• Sponsors, e.g. large biobanks, pharmaceutical and biotech companies
Mentored and Guided by the Biobank Steering Committee
• Chair: Brian Pettiford, MD
Express Bank
PathBank
Academic Collaborations
Leftover Biospecimens
Sponsored Projects
Processing
Formalin-fixed paraffin embedded (FFPE) tissue
from Pathology and prospectively collected
Specimens prospectively collected and banked for future research projects
Specimens collected, processed and stored for specific research project
with internal/external collaborators
Specimens collected for sponsored projects with specific inclusion criteria
Blood and tissue processing for other Ochsner clinical trials or external sources
Remnant specimens collected from clinical labs
that are targeted for disposal
OCHSNER BIOBANK:
Prospective Collections
Umbrella Informed Consent Form and Protocol• Most biospecimen project requests require the exact same specimen
types with the same patient risks, privacy and protection rules to be applied
• Allows collection of multiple different specimen types for one-time or longitudinal collections
• Only minimal risk specimens can be collected
• Language includes the following standard information told to every patient:
• Research is voluntary and likely has no direct benefit
• All specimens/data are de-identified
• Results will not be reported to the patient
• Specimens may be used for genomic studies, which has privacy risks
• Specimens may be shared with researchers, including internal, external and commercial sponsored researchers
• Types of current and future studies that may be performed using the specimens
• Including possible development of a cell line
• Length of time the specimens and/or records will be kept
Biospecimen Processing Room
OCHSNER BIOBANK:
Prospective Collections
Collections of specimens performed in conjunction with standard of care practices
• Reduce extra needle ‘sticks’
• Only collect resected tissue
• NEVER collect biopsies or materials needed for diagnostic purposes
We work very closely with clinical staff to ensure absolute patient safety and appropriate consent/collection of specimens
• Department of Pathology
• Clinical staff caring for a patient to be approached
• Dr. Meredith Lakey in the Biobank
OCHSNER BIOBANK:
Leftover Biospecimens
Consent waiver protocol in partnership with Clinical Pathology
Operational Standard governs the communication and appropriate workflow with each laboratory to ensure there is a chain of custody and appropriate handling
Specimens collected for clinical assessment targeted for disposal
• Fixed tissue from Pathology
• Biofluids from clinical pathology labs
o Blood
o Bronchoalveolar Lavages
o Remnant swab specimens
• Requires coordination with each clinical laboratory:
o Cytology
o Hematology
o Microbiology
o Molecular Biology
Specimens paired with limited data set and always deidentified when provided to researchers
OCHSNER BIOBANK:
Archival Pathology Specimens
Consent waiver protocol in partnership with Anatomic Pathology
Pathology FFPEs that are (>10 years) are not required to be kept by CAP/CLIA
• Operational standard to turn over governance of those specimens to the Ochsner Biorepository to be used for research
• Kept in locked storage rooms and all releases for research are managed by Pathbank research scientist
For FFPE specimens (<10 years old), we partner with Pathology for approval to provide for research
Prospective FFPEs
• Prospectively collected tissue fixed and made into FFPEs
• Reviewed by research pathologist/scientist, Dr. Meredith Lakey in the Biobank
• Like all other specimens, FFPE blocks and pathology reports and any other data provided are all redacted and de-identified
• Accession numbers considered a patient identifier/medical record number, and thus, are filed off and replaced with a unique identifier
OCSHNER BIOBANK MODEL
Cost Recovery Business Model:
• Recuperation of expenses
• Revenue from sponsored studies’ revenue helps financial sustainability
• 80% of operations are toward sponsored studies
• Most common prospective requests:
• Fresh blood shipped same day
• Processed blood to be frozen and batch shipped
• Fresh tissue shipped same day
• Most common retrospective requests:
• FFPEs
• Fees DO NOT pay for the specimen itself
• Never a higher fee for more tissue or blood
Fees cover TIME/EXPENSES:
• Study start-up
• Consent
• Collection
• Processing
• Part of study
• External processing from blood collected outside Ochsner
• Shipping
• Data mining/chart review
• Review and retrieval of specimens (PathBank FFPEs)
• Archival fees (leftover specimens)
OCHNSER BIOBANK
FACILITY AND EQUIPMENT
All equipment is monitored on a regular basis Daily monitoring with alerts for temperature storage Certifications of equipment every 6 months-1 year
Liquid nitrogen cryogenic storage tanks Allows for snap freezing tissue Allows long term storage of various biospecimens Have smaller tanks that are placed in the OR for direct snap freezing; retrieved
regularly
Ultra-low Freezer Storage Allows for long term storage of serum/plasma Allows for storage of clinical trials specimens
BSL-2 Capabilities
Tissue Processing/Paraffin Embedding Equipment Can generate FFPEs according to Pathology SOPs Microtome for cutting slides H&E staining station
Laboratory Information Management System Database of every specimen, aliquot location, etc Detailed labeling with barcode and scanning capabilities Serves as an enrollment log and specimen management software
Cryogenic Storage Room
BIOBANK SERVICES
Consultation on project design, outcome measures, etc.
Study start-up: contracts, MTAs, DUAs, IRB submission, etc.
Patient identification and consent
Specimen collection
Specimen processing: serum, plasma, PBMCs, fresh/frozen/FFPE tissue, etc.
Experimental assays*
Data collection/entry from the EMR
Collaboration with external partners to facilitate studies between institutions
Shipments to collaboratorsPBMC Isolation
HOW PANDEMICS
HAVE SHAPED BIOBANKING
The WHO and other countries have rapidly established protocols for biorepositories during epidemics (WHO.int; Ashcroft eta al. 2019)
• COVID19• 2014 Ebola Outbreak
o Large scale biorepositories were rapidly established
• Zika Virus Outbreak• Chickungunya virus Outbreak• Lassa Fever• MERS/SARS• Crimean Congo Hemorrhagic Fever
PROBLEMS WITH THE RUSH OF
BIOBANKING IN PANDEMICS
2014 Ebola Outbreak Swift meetings held in West Africa, particularly Sierra Leone
40 laboratories were involved Involved the West African Health Organisation and West African Task
Force for Emerging and Re-emerging infectious disease outbreaks (WATER)
Large volume of samples collected without much guidance Many not linked to clinical information Many not adequately inventoried, and thus not useful Safety of collection, processing, storage in question Many debates over whether specimens were already
destroyed Organization of efforts were rushed, and thus not ideal Different countries involved made it difficult to decide on
what defined informed consent
(WHO Report 2015)
HOW OCHSNER BIOREPOSITORY UNIT HAS APPROACHED COVID19 BIOBANKING
IRB Approval of Modified Consent Process• Verbal consent over telephone with use of consent witness• Patient Information Sheet• Phone Script
Several Different Operations Set Up to Obtain Different Patient Samples:
• Inpatient Consenting (hospital floor and ICU)o Coordination with Case Management team for LAR information for
ICU patientso Coordination with Unit Directors to get permission and to disseminate
information o Direct coordination with the nurse taking care of the patient for
specimen collectiono Coordination with phlebotomy for blood collections
• Testing Centers o Verbal consents occur while patients waiting in their car for testingo Coordination with the nurse and MA at MidCity Urgent Care
HOW OCHSNER BIOREPOSITORY UNIT HAS APPROACHED COVID19 BIOBANKING
Several Different Operations Set Up to Obtain Different Patient Samples (cont’d):
• Temporary Clinic Setups (partnering with Ansley and CTU):o Two clinics:
• COVID+ Patient Clinic• Convalescent Clinic (patients 14 days post symptoms)
o Coordinated with Infection Control for proper disinfection protocol
o Established teams with CRCs from all research teams with specific roles per day:
• Consenter• Consent Witness• Courier• Processor
o Once consented, they are scheduled for an appointment time, one at a time
• Leftover Biospecimenso Swab remnantso Blood remnants
BIOBANK STAFF AND CONTACT
INFO• Lyndsey Buckner Baiamonte, PhD- Supervisor
• Meredith Lakey, MD- PathBank Research Scientist
• Donnalee Trapani, LPN- Regulatory Coordinator
• Nicolle Crovetto, MS- Specimen Processing CRC
• Dorothy Breckner- CRC
• Abby Richardson- CRC: Baptist
• Santos Rodriguez-CRC: Kenner
• Rafael Velasquez Valle, MD- CRC
• Randi De’Armitt, MBA- CRC
MAIN BIOBANK NUMBER: (504) 842-2211
ACKNOWLEDGEMENTS
• The entire Biobank team, past and present!
• All upper leaders, including:• Samantha Bright • Edmund Kabagambe, DVM, PhD
• Ansley Hammons, MBA • The CTU Team
• Amy Feehan, PhD
• Keri Blouin, RN- Infection Control-Baptist
• Susan E Martinez, NP
• Julie Castex, CNS
• MidCity Urgent Care Team• Rachelle Simpson, RN• Jack Hebert- MA• Eunice Weckesser• Jatia Winters
• The Biobank Steering Committee• Brian Pettiford, MD• John Cole, MD• Rebecca Phillips, MD• Gretchen Galliano, MD• Sean Collins, MD• Sherri Longo, MD• Fawad Khan, MD• Ifeanyi Iwuchukwu, MD
THANK YOU ALL!Ansley Hammons
Randi De’Armitt
Dorothy Breckner
Susan E Martinez
Donnalee Trapani
Nicolle Crovetto
Rafael Velasquez Valle
Ellen Lovell
Nilmo Hernandez
DeAnna Ames
Lisa Edmond
JoEllen Johnson
Kathleen Arias
Santos Rodriguez Jr
Abby Richardson
Melissa Hendricks
Veronica Hixon-Calliet
Jenna Griffin
Kayla Barney
Nadrine Hayden
Ashley Sankey
Brittany Kiele
Sarah Cohen
Michelle Wilson
Kiyan McCormick
Sarah Seoane
Derek Wiltz
Michael Harrison
Nabami Malekera
Dana Comeaux
Daishun Gabriel
Jeannie Nguyen
Eve Youngberg
Amy Riehm
Angela Smith
Sharonda Brown
Craig Zibilich
Angel Penning
Jill Collins
Amanda Bailey
Julia Granchi
Julie Ketchens
Kathleen Arias
Laura Raymond
Hailey Anderson
Melinda Benvenuti
Shannon Williams
Laura Raymond
Maria Gloth
Maria Latsis
Elsa Levenes
Samantha Bright
ALL WHO HAVE PARTICIPATED IN BIOBANK EFFORTS, SERVED AS LEADERS, AND BEEN TEAM PLAYERS FOR COVID STUDIES!