1. Meetings with FDA Martha A. Feldman, RAC
Drug & Device Development Co., Inc.
UWE Biomedical Regulatory Affairs
Feldman Nov 2007

2. Topics for this Session
FDA’s views on meetings
Kinds of Meetings: drug/biotech and medical device products
Types of Meetings for PDUFA Products
Make request for a meeting
Prepare for Meeting
Participate in Meeting
Follow-up to Meeting
Miscellaneous
Feldman Nov 2007

3. FDA’s View of Meetings
FDA is committed to communicating and interacting with sponsors
FDA believes face-to-face meetings benefit both sponsor and agency
FDA believes meetings are cost-effective in the long run for both sponsor and agency
This slide and several of the following slides are abstracted from Elisa D. Harvey, “Understanding the Pre-IDE Program: FDA Perspective”, 25 May 2005
Feldman Nov 2007

4. Kinds of Meetings - 1 Drugs and Therapeutic Biologics
Pre-clinical Research Meeting
Pre-IND Meeting
End of Phase 2/Pre-Phase 3 Meeting
Clinical Hold Meetings
Pre-NDA Meeting
Advisory Committee Meeting
End of Review Conference
Refusal to File Conference
Pre-NDA Supplement Meeting
Feldman Nov 2007

5. Kinds of Meetings - 2 Medical Devices
Scientific Meeting/Prior to proof of concept animal studies
Early Collaboration Meetings (Agreement and/or Determination)
Pre-IDE Meeting/Post-feasibility/Pre-Pivotal Study Meeting
Informal Pre-IDE Meetings
Other Device Meetings
Pre-PMA Meeting
100-Day PMA Meetings
Post-deficiency letter for 510(k) or PMA
Appeal of final decision on PMA, 510(k), IDE disapproval
Advisory Committee Meeting
Feldman Nov 2007

6. FDA-SPONSOR MEETINGS - DRUGS
Feldman Nov 2007

7. Pre-clinical Research Meetings
Meetings are for the purpose of reaching agreements on the design and size of clinical study for effectiveness claim
Special Protocol, Pharm/Tox
Only on the pharm/tox portion
Special protocol, Chemistry
Only on the chemistry portion
Special Protocol, Medical
Only for the medical portion
Feldman Nov 2007

8. Pre-IND Meeting - 1
CDER needs data that the drug is reasonably safe for use in initial small-scale clinical studies
The sponsor would request a meeting with the appropriate review division.
Discussions will include animal protocols, clinical testing phases, data requirements, and scientific issues needing resolution prior to clinical studies
Feldman Nov 2007

9. Pre-IND Meeting - 2
Chemistry, Manufacturing and Controls (CMC) Pre-IND meeting may be part of clinical meeting or separate
Guidance document applies to both drugs and therapeutic biologics
Topics covered in the meeting depend on what Phase study is being conducted
Purpose: discuss CMC issues as they relate to the safety of the new drug/biologic for the proposed indication
Feldman Nov 2007

10. End of Phase 1
Sponsor may request a meeting after completion of Phase 1
Purpose is to review results and reach agreement on plans for Phase 2 program
Feldman Nov 2007

11. End of Phase 2/Pre-Phase 3 Meeting
Primary purpose: to determine if it is safe to proceed to Phase 3.
Secondary purpose: to plan the protocol for the Phase 3 study, e.g., the objectives, study design
Also, to discuss and identify any additional information that may be required to support a NDA.
Feldman Nov 2007

12. Critical Path Meeting
Meeting which is held to help with a stalled drug development program
Purpose is to help program proceed
Feldman Nov 2007

13. Clinical Hold Meeting
At any point, the CDER can impose a clinical hold, i.e., prohibit the study from proceeding or to stop a study that has started for reasons of safety, or because of a sponsor’s failure to disclose the risk of the study to the investigators.
Feldman Nov 2007

14. Pre-NDA/Pre-BLA meeting
Primary purpose: to discuss the data in support of the application – filing and format issues
Secondary purpose: to uncover any major unresolved problems or issues that might lead to a “refuse to file” recommendation
Also, to acquaint reviewers with the information submitted and to discuss how the data will be presented in the NDA.
Feldman Nov 2007

15. 90-Day Meeting Occurs 90 days after the initial submission
Purpose: to discuss any issues uncovered in the first stages of the review
Feldman Nov 2007

16. Advisory Committee Meeting
Purposes:
To solicit outside advice and opinions from experts
Recommendations are nonbinding on CDER
Issues that may be discussed
Opinion about a new drug
Opinion about new indication for an approved drug
Considerations about special regulatory requirements
Advice on necessary labeling
Help with proposed study
Assessing if safety and efficacy data are adequate support for the NDA
Feldman Nov 2007

17. End of Review Meeting
Sponsor requests meeting to determine what steps are needed to be completed by the sponsor, what additional information may be required in order for the application to be approved.
Feldman Nov 2007

18. Refusal to File Meeting
The sponsor may request in writing a meeting with CDER is it refuses to file an application
If, after the meeting, the sponsor wants the application, the FDA will do so under protest.
Feldman Nov 2007

19. Pre-NDA(BLA)/Supplement Meeting
The purpose of this meeting is to acquaint the FDA reviewers with the general information to be submitted
Discuss appropriate methods of statistical analysis
Discuss proposed format for data
To identify the major supporting studies
Discuss any unresolved issues
Feldman Nov 2007

20. Other Possible Meetings
Advertising and promotion issues
Biopharm and Bioequivalence
Compliance
Electronic submissions
Labeling
Phase 4
Safety Issues
Feldman Nov 2007

21. KINDS OF MEETINGS – MEDICAL DEVICES
Feldman Nov 2007

22. Scientific/Pre-proof of Concept Testing
Discuss concepts, broad outline of test plans, including need for certain bench studies, need for animal studies and need for clinical studies (no test results needed, just plans, at this meeting)
Discuss regulatory options, possible pathways
Discuss primary mode of action issues of a possible combination product; jurisdictional issues
Feldman Nov 2007

23. Early Collaboration Meetings http://www.fda.gov/cdrh/ode/guidance/310.html
Present early prototype evaluation in preliminary animal models
Discuss proposed clinical application, indication for use
Get FDA feedback on bench and animal study plans; feasibility study plans.
Start asking specific questions (e.g., patient population; acceptable endpoints)
Discuss probable regulatory pathway (non-binding discussion), including Risk Determination for device (SR/NSR)
Feldman Nov 2007

24. Pre-IDE Meeting/Post-feasibility/Pre-Pivotal Study Meeting
Sponsor presents results of animal and feasibility study; describe finalized device design
Sponsor discusses pivotal trial protocol (1° and 2° endpoints, duration, statistical analysis and evaluation methods), including Indication for Use and patient population
FDA gives feedback on above and on proposed regulatory pathway, and nonbinding feedback on expedited status, need for Advisory Panel meeting
FDA gives feedback on focused questions
Feldman Nov 2007

25. Pre-IDE Meetings Are Are Not
To provide feedback on preclinical test plan
To provide feedback on clinical plans
Determine what is Exempt/NSR investigation
To discuss international (OUS) studies
Are Not
A tool for negotiation
For modular review
To preview data
For an in depth IDE review
Legally binding
For dispute resolution
To hold FDA to years-old informal feedback
To be part of a series of such meetings
Feldman Nov 2007

26. Informal Pre-IDE Meetings
Not determination or agreement meetings
Nothing binding
May not have full review team present
Individual divisions may have their own checklists about what to submit prior to the meeting – ascertain prior to sending package
Feldman Nov 2007

27. Other Device Meetings Pre-PMA Meeting 100-Day PMA Meeting
Post-deficiency letter for 510(k) or PMA
Appeal of final decision on PMA, 510(k), IDE disapproval
Feldman Nov 2007

28. Advisory Panel Meeting
Requirements (Section 513(b)(6)(B)
Must have adequate time for initial presentation
Must have adequate time provided for response to any differing views by persons whose devices are the subject of a classification panel
Must encourage free and open participation by all interested persons
Feldman Nov 2007

29. Advisory Panel Sponsor sends FDA material on Panel presentation
FDA sends to the Sponsor the list of items it will include in package to members of the Panel
FDA sends package of materials to Panel members; no new data provided within last 2 weeks prior to meeting
Time lines for presentation to the Panel are provided in guidance document
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30. FDA Does Not Have to Accept Recommendations from the Panel
Feldman Nov 2007

31. Applies to both CDER and CBER
TYPES OF MEETINGS
Applies to both CDER and CBER
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32. Type A
Is immediately necessary for a stalled drug development program to proceed
Occur within 30 days of sponsor’s request
Examples:
Dispute resolution meetings
Clinical holds
Special protocol assessment after FDA evaluation
Feldman Nov 2007

33. Type B Scheduled 60 days after receipt of sponsor request
Pre-IND meeting (21 CFR )
Certain end of Phase 1 meetings (21CFR )
End of Phase 2/Pre-Phase 3 meetings (21 CFR )
Pre-NDA/BLA meetings (21 CFR )
Feldman Nov 2007

34. Type C Any meeting other than a Type A or a Type B meeting
Examples of such meetings
About advertising
About promotional labeling
Not Type C meetings – examples
about launch activities and materials
Postmarketing safety evaluation meetings
Feldman Nov 2007

35. Requesting a Meeting with FDA
Feldman Nov 2007

36. Whom to Meet With
Check Center’s organizational chart to determine to which group to send meeting request
Call the division and give a brief overview of why a meeting is being requested, i.e., the purpose and scope of the meeting; give regulatory status of the product (e.g., new, re-vamped in some way, new indication for previously approved product)
Get a name of the person to whom the package should be addressed, usually the Branch Chief
The package must be received before a meeting is scheduled, usually about 2-3 weeks in advance.
Feldman Nov 2007

37. Setting a date
Be flexible as to dates – give several possible dates and times.
NOTE: If significant additional information is submitted after the package has been sent and after the meeting has been scheduled, the meeting might be cancelled or postponed.
If you have to cancel, do it at least 48 hours ahead.
Feldman Nov 2007

38. The CDER/CBER “Package” Includes:
Proposed agenda; list of attendees and affiliations
Product name, chemical name and structure
Proposed indication(s)
Dosage form, route of administration, dosing
Study plans: bench, animal, clinical
Summaries of prior animal or clinical data (as appropriate for phase of study)
Chemistry, Manufacturing and Controls (as appropriate for Phase of study)
List of objectives/outcomes expected from meeting
Feldman Nov 2007

39. The Device “Package” Includes:
Proposed agenda (and time allotment) and list of attendees and each person’s affiliation
Background of clinical condition or disease
Currently available products, balanced view of pros and cons of each
Product description and rationale for use in this condition or disease
intended use and indication for us
Test plans: bench, animal, clinical
List of questions to be addressed at meeting
Feldman Nov 2007

40. What FDA does when it Receives the Package
Branch chief receives package
BC determines who will be on Review Team
BC assigns project to a lead reviewer
Copies prepared (or requested of Sponsor) and distributed
Internal pre-meeting and sponsor meetings are scheduled
Team members review package and prepare memos prior to pre-meeting
Internal pre-meeting held to discuss issues, reach consensus, get further information from Team/management
Feldman Nov 2007

41. Preparing for a Meeting with FDA
Feldman Nov 2007

42. Planning the Presentation-1
Use the time optimally.
Presentation of the agenda and list of attendees should take no more than 2 minutes
Assume the FDA has read all of the material; do not waste time in your presentation reviewing material sent in the package.
Call a week ahead of meeting to see if the Lead Reviewer can send you a list of the questions generated at their internal meeting.
Feldman Nov 2007

43. Planning the Presentation - 2
The preliminary questions from the reviewing team may cover deficiencies and/or other issues
Compare your list of questions with the preliminary questions from the review team. Ensure your presentation will cover them and, if possible, without presenting significant new information.
Focus your presentation to elicit as much information, comments, suggestions from the agency.
Manage the time by rehearsing presenters so that they keep to their time allotment.
Limit the number of presenters – too much time can be lost during change of speakers.
Feldman Nov 2007

44. Preparing for the Meeting
Do a mock rehearsal with two groups of people:
Those that know a lot about the product and research - to ensure you have not omitted critical information and have included all possible issues
Those that do not know anything abut the product and have read only the “package” - to ensure your presentation is comprehendible and flows smoothly
Feldman Nov 2007

45. Participating in a Meeting with FDA
Feldman Nov 2007

46. The Meeting - 1
Get to the building early as there is a lengthy sign-in and inspection procedure.
Meetings are usually one hour long. They will start and end on time.
TURN OFF CELL PHONES AND PAGERS!
There will be a sign-in sheet circulated during the meeting, which will be copied for the sponsor.
Stick to the agenda.
Feldman Nov 2007

47. The Meeting - 2
Manage the time well. Leave small talk to the end, if there is time.
Be brief and stay focused on scope of meeting.
No side conversations.
No open-ended questions.
If the group gets bogged down on one issue, suggest that the one issue be handled off-line and continue with the other topics.
Ensure that at least one person from your company is taking notes during the meeting.
Feldman Nov 2007

48. The Meeting - 3
While taking notes, mark the items that are action items,
commitments for providing follow-up information to the company
commitments for providing follow-up information to the FDA,
arranging for off-line discussions
Make sure there is about 10 minutes at the end of the meeting to review the Action Item list.
Get a copy of the attendees list.
Feldman Nov 2007

49. Follow-Up After a Meeting with the FDA
Feldman Nov 2007

50. Debrief
As soon as possible after the meeting, gather the company representatives to debrief
As part of the debriefing, get people’s perceptions of the reaction to the presentation of each member of the FDA’s Team
Assess if there may be any misunderstandings or mistaken impressions by anyone – can expand upon some things in the minutes or add an addendum with clarification
See if you may have “supporters”
Feldman Nov 2007

51. Minutes of the Meeting
Have one person take everyone’s notes and draft the minutes, including a section for the action items
Distribute to the other attendees for review in order to ensure full capture of information, commitments, etc.
Issue minutes to management
Send to FDA with a cover letter asking for comments
Feldman Nov 2007

52. Miscellaneous Information
Feldman Nov 2007

53. References - Drugs
CDER Data Standards Manual: Industry Meetings Types
Formal meetings – PDUFA Products
Clinical Hold/Refusal to file Meetings
CMC IND Meetings
The New Drug Approval Process
Feldman Nov 2007

54. References - Devices
Early Collaboration Meetings under FDAMA - Meeting guidance
Advisory Panel Meetings
Advisory Panel/Committee Information Contact
Feldman Nov 2007