mark a. del vecchio director, regulatory and clinical affairs digene corporation
DESCRIPTION
How to Work with FDA: Industry Perspective IVD Roundtable/OIVD Workshop. Mark A. Del Vecchio Director, Regulatory and Clinical Affairs Digene Corporation. April 22, 2003. Discussion Topics. Interaction with FDA General Considerations Before you Submit During the Review - PowerPoint PPT PresentationTRANSCRIPT
Mark A. Del VecchioDirector, Regulatory and Clinical Affairs
Digene Corporation
How to Work with FDA:Industry Perspective
IVD Roundtable/OIVD Workshop
April 22, 2003
Discussion Topics
Interaction with FDA General Considerations Before you Submit During the Review In the Home Stretch
Meetings with FDA
Use of Consultants Regulatory Statistical
Quality of Submitted Documents
Interaction with FDAGeneral Considerations
In the regulatory arena, your Company’s success is highly dependent on your working relationship and reputation with FDA
You have the right and the obligation to work with the Agency on your submission strategies
Be as up front as possible regarding your proposed submission strategy…it is important not to surprise the Agency
Honor the resulting commitments
Interaction with FDAGeneral Considerations
Document all of your communications with FDA This will help both you and FDA to easily refer to
specifics of items discussed/agreed upon Expands internal Company communication,
clarifying corporate objectives when addressing issues with FDA
It is imperative that you discuss submission options with the appropriate review branch, particularly when proposing an “express” or novel route
Interaction with FDABefore you Submit
Establish which Center/ OIVD Division will review your submission
Determine the appropriate submission type
Discuss your proposed clinical study and submission with FDA review team
Draft Clinical Protocol should be available Including the statistical analysis plan for the
study data
Interaction with FDABefore you Submit
It is critical that you have the Intended Use for the test clearly defined
This is the mechanism whereby FDA can determine the appropriateness of your clinical study to support the intended claim(s)
Significant time should be dedicated to ensuring FDA understands your claims and the type of data:
FDA expects to support these claims You propose will adequately support these claims
Be prepared to provide rationale for the statistical approach to support your claims
Interaction with FDABefore you Submit
Agreement on clinical trial design and submission strategy is very important
Amount of upfront discussion dependent on complexity and “unique” nature of the approach
Traditional approach – fewer unknowns
It is appropriate to discuss statistical issues directly with FDA statistician when necessary to minimize confusion or to clarify FDA’s position
Interaction with FDABefore you Submit
Be prepared Use CDRH/CBER Guidance Documents Review Other Clearance/Approval Information
– CDRH/CBER Website– FOI
Talk with other Industry RA professionals:– ADVAMED– AMDM– RAPS
Utilize regulatory and statistical consultants where appropriate
Interaction with FDABefore you Submit
Major objectives of earlier interactions - to reach a common understanding with FDA regarding your plan to support the intended use you are evaluating via pre-clinical and clinical studies
Meet with FDA as often as necessary before submission until both parties are comfortable with approach
Minimal goal is to reach philosophical agreement with FDA on the approach, however, things could change
Try to minimize areas that could change as you go along
Bring major changes back to FDA for discussion
Often times, FDA will request additional information in a fairly informal manner, handled primarily via phone and/or email
Only when the request is substantive will FDA issue a formal deficiency letter or written request for additional information; typically near the end of the review cycle
Try to work with FDA to get more statistical review feedback DURING the review
Interaction with FDADuring the Review
Much statistical discussion should take place before submission; however,
sometimes specific details not available until after a decision is made
atypical, but has occurred on several occasions recently
Work with OIVD to ensure that you have the opportunity to address statistical concerns prior to a decision
One reason it is critical to reach some form of agreement on statistical plan before start of the study and prior to submission
Interaction with FDADuring the Review
Just prior to an FDA decision (2-3 weeks)
Most of the technical details worked out…FDA has a good understanding of the results of your clinical study and data available to support application
Much of this time spent on the specific details of the product labeling (PI)
May involve modifying your intended use statement to better reflect study data
The type/extent of data that can be included in the PI will be discussed
Last minute administrative details are addressed
Interaction with FDAIn the Home Stretch
Very critical period, since time often running out to make a decision
Respond quickly to FDA requests
Utilize email as much as possible…good means to communicate
Accurate, written record Very rapid Can submit hard-copy email comms with final
amendment if requested by Reviewer
Interaction with FDAIn the Home Stretch
Meeting with FDA
When first formulating your regulatory approach
Submission type Correct review branch/division
Prior to initiation of clinical study Draft clinical protocol should be available Proposed Intended Use Data analysis plan
Recommended points in the process to meet with FDA (teleconference or face-to-face):
Meeting with FDA
Prior to Submission following initial data analysis particularly if statistical issues were raised
during earlier meetings
During the review if necessary to respond to questions/identified deficiencies
with the application
Recommended points in the process to meet with FDA (teleconference or face-to-face):
Provide talking points prior to the call, if time permits
Determine the participants required on the call, both for you and FDA
Sometimes a one-on-one with the Lead Reviewer is best
FDA is very responsive to setting up teleconferences in a timely manner
Gone are the days you could not contact your reviewer for several days
Meeting with FDA Whenever you teleconference with FDA :
Provide agenda, talking points, data package prior to meeting at least 1 week in advance
Allow 3-4 weeks to schedule meeting with FDA; schedules are tight and you want all the essential people in the room when discussing your submission
Decide whether a formal presentation is appropriate…recommended approach
Conduct several “rehearsals” in-house prior to the meeting
Meeting with FDA Whenever you meet face-to-face with FDA :
Have your regulatory and/or statistical consultants with you for the meeting
FDA will always have a statistician participate in the meeting, particularly if clinical trial design or data analysis is being discussed
Before the meeting, prepare questions (with the responses) you anticipate FDA will ask
Have your technical staff with you as well, particularly to address unanticipated questions from the Review Team
Meeting with FDA Whenever you meet face-to-face with FDA :
Serves to resolve any miscommunication immediately
Helps facilitate clear understanding of action items and time commitments
Meeting with FDA
Follow-up after the meeting with minutes to your Lead Reviewer or a “Memo of Understanding” so that key points and decisions made during the meeting are documented
Highly recommended when interacting with FDA, particularly if you:
Are taking a novel approach New to the industry Bringing a product to a different review
branch/division or Center Do not have dedicated in-house statistical support
Typically have a greater range of contacts and experience with FDA
Can suggest approaches taken in other Centers or other Divisions within ODE/OIVD
Provide objective external review of submission
Utilizing Consultants
The success of your submission is greatly dependent on FDA’s ability to read and understand the document
Pre-submission interaction will greatly enhance the quality and clarity of the documents
Respect the fact that FDA reviewers handle several submissions simultaneously and therefore must make very efficient use of time spent on a single submission
Very important that the information in the submission build on an orderly presentation of history, facts, and data
Quality of Submitted Documents
Well-organized TOC Clear, consistent pagination Labeled section tabs
Thorough, clear, and concise in your descriptions
Use Summary Tables as much as possible Do not assume FDA “remembers”:
– Conversations– Prior submissions– Details of your product
Quality of Submitted DocumentsIt is imperative that your documents are:
If it is critical that a particular point be communicated to FDA, repeat it several times in different sections of the application
Always reiterate important background information
If your submission is lengthy, use this tactic more often
When cross-referencing other submissions or even volumes of same submission, provide a summary of information to eliminate “flipping back and forth” between documents
When responding to specific FDA questions, always restate the question immediately prior to your written response
Quality of Submitted Documents
When reviewing documents internally prior to submission, assume no prior knowledge
Have an outside party review documents Regulatory consultant Statistical consultant Another department member within your
organization, but not involved in the project
Quality of Submitted Documents
Confusing, mis-numbered tables
Poor organization
Improper pagination
Wordy, unclear text
Quality of Submitted Documents
All of these lead to:
Frustration
Misunderstandings
Unnecessary, redundant communications
Multiple Review cycles
Increased review times