SUCCESSFUL FDA MEETINGS DIA West Coast Drug Development Conference San Francisco, CA October 25, 2004

1
SUCCESSFUL FDA MEETINGS DIA West Coast Drug
Development ConferenceSan Francisco, CA
October 25, 2004

• Michael A. Swit, Esq.
• FDACounsel.com
• THE LAW OFFICES OF MICHAEL A. SWIT
• 539 Samuel Ct., Suite 229
• Encinitas, CA 92024
• 760-815-4762 ? fax [phone]
• mswit_at_fdacounsel.com
• www.FDACounsel.com

2
Overview of Tutorial

• Part 1 -- The Law of Meetings
• Part 2 FDAs Guidances, etc., on FDA
  Meetings
• Part 3 Details on the Different Types of
  Meetings
• Part 4 Tips and Traps
• Part 5 Q A

3
What Were Not Covering

• Advisory Committee Meetings
• Medical Device Meetings
• Exit Interviews meetings following FDA
  inspections
• Public meetings, other than Advisory Committee
  meetings (e.g., Sept. 2004 meeting on follow-on
  generics)
• Hearings (e.g., Clinical Investigator
  Disqualification)
• Meetings attended by FDA officials outside the
  agency (e.g., conferences, ICH meetings)
• Formal dispute resolution processes

4
Part 1

• The Law of Meetings

5
Where to Go for Perspective or What is the Law
Governing FDA Meetings?

• Law School in 60 seconds
• What is law?
• U.S. Constitution
• Statutes Federal Food, Drug, and Cosmetic Act
  (the Act)
• Regulations force and effect of law 21 CFR
  Part 54

6
Where to Go for Perspective or What is the Law
Governing FDA Meetings?

• FDA advisory opinions formal position of FDA
  binding until refuted FDA cant take regulatory
  action vs. someone who relies on an FDA advisory
  opinion 21 CFR 10.85(e)
• Preambles to proposed or final rules an
  advisory opinion 21 CFR 10.85(d)(1)
• Common law case law

7
Where to Go for Perspective or What is the Law
Governing FDA Meetings?

• Whats not law?
• Anything else FDA writes guidances, speeches,
  warning letters, complaints in Federal court
• Guidance
• describes the agencys interpretation of or
  policy on a regulatory issue 21 CFR
  10.115(b)(1)
• do not legally bind the public or FDA 21
  CFR 10.115(d)(1)
• But by statute

8
FDA Duty On Complying with Guidance Documents

• Section 701(h)(l)(B) of FFDCA
• Although guidance documents shall not be
  binding on the Secretary, the Secretary shall
  ensure that employees of the Food and Drug
  Administration do not deviate from such guidances
  without appropriate justification and supervisory
  concurrence.

9
Where to Go for Perspective or What is the Law
Governing FDA Meetings?

• So, where do we find the law of Meetings?
• NOT
• in Constitution or the Common Law (for the most
  part)
• YES
• Statutes but only rarely
• Regulation but only in fairly general terms
  21 CFR 10.65

10
Where to Go for Perspective or What is the Law
Governing FDA Meetings?

• The rest is commentary
• Various guidance documents to be discussed in
  detail in Part 2 of this tutorial
• FDA presentations at DIA, RAPS, etc.
• Caution the commentary requires careful
  attention

11
Federal Food, Drug, and Cosmetic Act (FFDCA)
Provisions Governing FDA Meetings

• Section 505(b)(4) added by Section 119 of The
  Food Drug Modernization Act of 1997 (FDAMA)
• or
• The FDA cant change its mind unless theres
  new safety/effective data clauses.

12
Section 505(b)(4)(B)

• The Secretary shall meet with a sponsor of an
  investigation or an applicant for approval for a
  drug under this subsection or section 351 of the
  Public Health Service Act if the sponsor or
  applicant makes a reasonable written request for
  a meeting
• for the purpose of reaching agreement on the
  design and size of clinical trials intended to
  form the primary basis of an effectiveness
  claim....
• The sponsor or applicant shall provide
  information necessary for discussion and
  agreement on the design and size of the clinical
  trials....
• Minutes of any such meeting shall be prepared by
  the Secretary and made available to the sponsor
  or applicant upon request.

13
Section 505(b)(4)(C)

• Any agreement regarding the parameters of the
  design and size of clinical trials of a new drug
  under this paragraph that is
• reached between the Secretary and a sponsor or
  applicant
• shall be reduced to writing and made part of the
  administrative record by the Secretary.
• Such agreement shall not be changed after the
  testing begins, except--

14
Section 505(b)(4)(C)

• with the written agreement of the sponsor or
  applicant or
• pursuant to a decision, made in accordance with
  subparagraph (D) by the director of the reviewing
  division, that a substantial scientific issue
  essential to determining the safety or
  effectiveness of the drug has been identified
  after the testing has begun.

15
Section 505(b)(4)(D)

• A decision under subparagraph (C)(ii) by the
  director shall be in writing
• and the Secretary shall provide to the sponsor or
  applicant an opportunity for a meeting at which
  the director and the sponsor or applicant will be
  present and
• at which the director will document the
  scientific issue involved.

16
FDA Regulations on Meetings

• 21 CFR 10.3
• Meeting means any oral discussion, whether by
  telephone or in person.
• 21 CFR 10.65
• (a) In addition to public hearings and
  proceedings established under this part and other
  sections of this chapter, meetings may be held
  and correspondence may be exchanged between
  representatives of FDA and an interested person
  outside FDA on a matter within the jurisdiction
  of the laws administered by the Commissioner.
• Action on meetings and correspondence does
  not constitute final administrative action
  subject to judicial review under 10.45.

17
FDA Regulations on Meetings

• 21 CFR 10.65(c)
• (c) Every person outside the Federal Government
  may request a private meeting with a
  representative of FDA in agency offices to
  discuss a matter. FDA will make reasonable
  efforts to accommodate such requests.
• (1) The person requesting a meeting may be
  accompanied by a reasonable number of employees,
  consultants, or other persons with whom there is
  a commercial arrangement within the meaning of
  20.81(a) of this chapter....

18
FDA Regulations on Meetings

• 21 CFR 10.65(c)
• (2) FDA will determine which representatives of
  the agency will attend the meeting.
• The person requesting the meeting may request,
  but not require or preclude, the attendance of a
  specific FDA employee.

19
FDA Regulations on Meetings

• 21 CFR 10.65(d)
• FDA employees have a responsibility to meet with
  all segments of the public to promote the
  objectives of the laws administered by the
  agency.
• Note rest of this subsection (d) deals with
  meetings outside of FDA

20
FDA Regulations on Meetings

• 21 CFR 10.65
• (e) An official transcript, recording, or
  memorandum summarizing the substance of any
  meeting described in this section will be
  prepared by a representative of FDA when the
  agency determines that such documentation will be
  useful.
• (f) FDA promptly will file in the appropriate
  administrative file memoranda of meetings
  prepared by FDA representatives
• and
• all correspondence, including any written
  summary of a meeting from a participant, that
  relate to a matter pending before the agency.
• (g) Representatives of FDA may initiate a meeting
  or correspondence on any matter concerning the
  laws administered by the Commissioner. Unless
  otherwise required by law, meetings may be public
  or private at FDAs discretion.

21
FDA Regulations on Meetings

• 21 CFR 10.70 the Administrative Record
• (b) FDA employees responsible for handling a
  matter are responsible for insuring the
  completeness of the administrative file relating
  to it.
• The file must contain
• (1) Appropriate documentation of the basis for
  the decision, including relevant evaluations,
  reviews, memoranda, letters, opinions of
  consultants, minutes of meetings, and other
  pertinent written documents
• (d) Memoranda or other documents that are
  prepared by agency employees and are not in the
  administrative file have no status or effect.

22
FDA Regulations on Meetings

• IND Regulations 21 CFR Part 312
• 312.47 -- Meetings (a) General. Meetings between
  a sponsor and the agency are frequently
  usefulduring the course of a clinical
  investigation.
• 312.82 Early consultation For products intended
  to treat life-threatening or severely
  debilitating illnesses, sponsors may request to
  meet with FDA-reviewing officials early in the
  drug development process

23
Part 2

• FDAs Guidances, etc., and The Handling of FDA
  Meetings

24
What Are the Guidances on Meetings

• Formal Meetings with Sponsors and Applicants for
  PDUFA Products. CBER/CDER, February 2000.
  http//www.fda.gov/cder/guidance/2125fnl.pdf
• Good Review Management Principles for PDUFA
  Products. CDER/CBER. July 2003.
  http//www.fda.gov/cber/gdlns/reviewpdufa.pdf
• Manual of Policy and Procedure (MaPP) 4512.1
  Formal Meetings Between CDER and CDERs External
  Constituents. CDER, March 1996.
  http//www.fda.gov/cder/mapp/4512-1.pdf

25
What Are the Guidances on Dispute Resolution

• Formal Dispute Resolution Scientific and
  Technical Issues Related to Pharmaceutical CGMP.
  CDER/CBER/ORA/CVM, August 2003.
  http//www.fda.gov/cber/gdlns/formaldis.pdf
• Formal Dispute Resolution Appeals Above the
  Division Level. CDER/CBER, February 2000.
• http//www.fda.gov/cber/gdlns/dispute.pdf
• Manual of Policy and Procedure (MaPP) 4151.1
  Resolution of Disputes Role of Reviewers,
  Supervisors, and Management Documenting Views and
  Findings and Resolving Differences. CDER, August
  1996. http//www.fda.gov/cder/mapp/4151-1.pdf

26
What Are the Guidances on Dispute Resolution

• Manual of Policy and Procedure (MaPP) 4150.1
  Role and Procedures for the CDER Ombudsman.
  CDER, October 2002. http//www.fda.gov/cder/mapp/4
  150.1.pdf
• Also see
• Guidance for Review Staff and Industry (Draft)
  Good Review Management Principles for PDUFA
  Products. CDER/CBER, July 2003.
  http//www.fda.gov/cber/gdlns/reviewpdufa.pdf
• Guidance for Industry Special Protocol
  Assessment. CDER/CBER, May 2002.
  http//ww.fda.gov/cber/gdlns/protocol.pdf

27
Formal Meeting Guidance

• Relates to PDUFA products see 735(1) of FFDCA
  for list of products
• The guidance document describes procedures for
  requesting, scheduling, conducting, and
  documenting such formal meetings.common to all
  CDER CBER review divisions.

28
Formal Meeting Guidance

• Designed to
• Cover all formal meetings i.e., any formal,
  planned interaction between FDA and an external
  constituent that occurs face-to-face, via
  teleconference or via video conference
• Also implements 119(a) of FDAMA
• note that 119(b) of FDAMA covers similar
  binding agreement language relative to ANDAs
  and was to be covered by a separate meetings
  guidance (not issued yet)
• 119(a) meetings are those that relate to
  special protocol assessments
• Incorporates procedures covered by CDER MaPP
  4512.1 and CBER SoPP 8101.1
• Not applicable to informal meetings which are
  not intended to be replaced by the formal meetings

29
Formal Meeting Guidance Types of Meetings
A,B,C

• Type A Meeting
• one that is immediately necessary for an
  otherwise stalled drug development program to
  proceed (i.e., a critical path meeting)
• Generally reserved for
• Dispute resolution meetings
• Clinical hold discussions
• Special protocol assessment meetings requested by
  sponsors after FDAs evaluation of protocols
  submitted via assessment letters

30
Formal Meeting Guidance Types of Meetings
A

• Scheduling of Type A meeting
• Within 30 days of FDAs receipt of a written
  request or
• If sponsor requests a later date, within 14 days
  of the requested date

31
Formal Meeting Guidance Types of Meetings
B

• Covers
• Pre-IND meetings (21 CFR 312.82)
• Certain end-of-Phase 1 meetings (21 CFR 312.82)
• End of Phase 2/pre-Phase 3 meetings (21 CFR
  312.47)
• Pre-NDA/BLA meetings (21 CFR 312.47)

32
Formal Meeting Guidance Types of Meetings
B

• Scheduling of Type B meeting
• Within 60 days of FDAs receipt of a written
  request or
• If sponsor requests a later date, within 14 days
  of the requested date

33
Formal Meeting Guidance Types of Meetings
B

• Caveats
• generally only one of each kind of Type B
  meeting for each potential application or
  combination of closely related products (e.g.,
  same active ingredients, different dosage forms)
• But, simultaneous development of a drug for
  unrelated claims may allow more than one of each
  kind of Type B meeting

34
Formal Meeting Guidance Types of Meetings
C

• Covers
• any meeting other than a Type A or B
• Must still relate to the NDA/BLA for the PDUFA
  product. Thus, not applicable to
• Advertising, except pre-launch activities
• Post marketing safety evaluation meetings

35
Formal Meeting Guidance Types of Meetings
C

• Scheduling of Type C meeting
• Within 75 days of FDAs receipt of a written
  request or
• If sponsor requests a later date, within 14 days
  of the requested date

36
Formal Meeting Guidance Requesting Procedures

• Written request (fax or letter) to
• CDER
• Appropriate division director within
• Office of Review Management (ORM)
• Office of Pharmaceutical Sciences (OPS)
• Office of Medical Policy (e.g. for DDMAC)
• If Type A, copy office director in ORM or OPS,
  when appropriate
• CBER appropriate division director with review
  responsibility or Advertising and Promotional
  Labeling Staff (APLS)

37
Formal Meeting Guidance Requesting Procedures

• If pre-IND, request goes to the appropriate
  division director
• Technical form of request an amendment
• IND stage via 1571
• NDA/BLA via 356h (in triplicate)
• If faxing
• contact division ahead of time to confirm who
  should get request
• Follow with hard copy submission
• Note if sent after hours (confirm ahead of
  time), will be deemed received next business day

38
Formal Meeting Guidance Requesting Procedures

• Contents of Meeting Request adequate
  information for FDA to decide utility of
  meeting and to identify the Agency staff
  necessary to discuss proposed agenda
• Specifically
• Product name and application (if any)
• Chemical name and structure
• Proposed indications
• Type of meeting sought
  (continued)

39
Formal Meeting Guidance Requesting Procedures
Contents of Request Letter

• Specifically
• Brief statement of meeting purpose
• Types of completed or planned studies or data to
  be discussed
• General nature of critical questions to be asked
• How meeting fits in overall development plans
• List of specific objectives/outcomes sought
• Preliminary proposed agenda
• time needed per item
• Designated speaker (continued)

40
Formal Meeting Guidance Requesting Procedures
Contents of Request Letter

• Specifically
• Draft list of questions, by discipline
• Chemistry
• CMC Microbiology (if applicable)
• Pharm/Tox
• Clinical Pharmacology Biopharmaceutics
• Clinical Microbiology
• Clinical
• Biostatistics
• Administrative Regulatory

41
Formal Meeting Guidance Requesting Procedures
Contents of Request Letter

• Specifically
• List, w/titles, of all to attend for sponsor
• Agency staff requested to attend or disciplines
  of identity not certain
• Approximate date supporting documen-tation will
  arrive Information Package
• Suggested dates and times
• ? some divisions will tell you the date/time
  prior to submitting request call ahead to check
  on this

42
Formal Meeting Guidance Requesting Procedures
FDA Handling

• Division director to promptly decide whether to
  hold meeting
• Review division to respond within 14 days of
  receipt.
• Response will include
• Date, time, place and length of meeting
• Expected FDA participants

43
Formal Meeting Guidance Requesting Procedures
FDA Handling

• If denied, FDA reply should include a clear
  explanation of the reason(s) for denial
• Subsequent requests new requests (clock starts
  over)
• Cancellation or postponements
• By applicant/sponsor starts new cycle
• By FDA to be rescheduled within 30 days

44
Formal Meeting Guidance Requesting Procedures
The Information Package

• FDAs receipt of a full information package,
  including clear, thoughtful questions, in advance
  of a formal meeting with sufficient lead time to
  enable Agency staff to review the data adequately
  is critical to achieving a productive
  meeting. Guidance, at page 6 (italics in
  original)

45
Formal Meeting Guidance Requesting Procedures
The Information Package

• Timing when to submit
• Type A at least 2 weeks before
• Type B at least 4 weeks before
• Type C at least 2 weeks (but 4 is recommended)
  before
• Failure to timely submit FDA may postpone or
  cancel

46
Formal Meeting Guidance Requesting Procedures
The Information Package Contents

• Product name and application (if any)
• Chemical name and structure
• Proposed indications
• Dosage form, route of administration, and dosing
  regimen (frequency duration) (continu
  ed)

47
Formal Meeting Guidance Requesting Procedures
The Information Package Contents

• Brief statement of purpose of meeting
• Types of completed or planned studies or data to
  be discussed
• General nature of critical questions
• Where meeting fits in overall development
• List of specific objectives/outcomes expected
• Proposed agenda
• Time for each item
• Designated speakers (continued)

48
Formal Meeting Guidance Requesting Procedures
The Information Package Contents

• List of specific questions by discipline
• Clinical data summary (as appropriate)
• Preclinical data summary (as appropriate)
• Chemistry, manufacturing and controls information
  (as appropriate)
• ? -- update any changed info from meeting request

49
Formal Meeting Guidance Requesting Procedures
The Information Package

• Format
• Cover letter identify date, time and subject of
  meeting
• Organize contents according to the proposed
  agenda
• Fully paginated
• Table of contents
• Indices
• Cross references
• Tabs for differentiating sections
• Copies of FDA participants 5

50
Formal Meeting Guidance Conduct of the Meeting

• FDA Chair
• Introductions (sign-in sheet)
• Identify who will record minutes and keep time
• At end, should summarize
• All important discussion points
• Decisions
• Recommendations
• Agreements
• Disagreements
• Issues for further discussion (note not in
  guidance here, but is to be included in minutes)
• Action items

51
Formal Meeting Guidance Conduct of the
Meeting

• Attendees should be given an opportunity to
  comment, including critical items believe should
  be in minutes
• Chair attempts to resolve any differences
• FDA recorder should document the summary as
  the official minutes.

52
Formal Meeting Guidance Documentation of
Meeting

• Minutes summarize, in bulleted form
• Important discussion points
• Decisions
• Recommendations
• Agreements
• Disagreements
• Issues for further discussion
• Action items

53
Formal Meeting Guidance Documentation of
Meeting

• Sponsors/applicants role vis-à-vis minutes
• May provide a draft
• If do so, DO PROMPTLY
• If done, will be considered in preparing
  official minutes
• FDA normally wont comment on sponsors draft
  unless it reflects major differences in view of
  meetings outcomes
• If major differences identified, sponsor should
  raise these with the review division initially

54
Formal Meeting Guidance Dispute Resolution

• Clarifications contact project manager to
  arrange teleconference
• Changes letter to Division Director, with a copy
  to the Project Manager, citing requested change
  reason
• ? -- give project manager heads up youre
  pursuing this
• Project manager issues response in writing
• Changes agreed to by FDA an addendum
• Sponsor if still not happy, pursue dispute
  resolution

55
Part 3

• THE DIFFERENT MEETINGS

56
When to meet with FDA?

• What FDA suggests (see yellow ?)
• Source Regulatory Review of New Drugs, Carol
  Cavanaugh, CDER, presented at MLA 2004,
  Washington, DC, May 24, 2004

57
The Pre-IND Meeting

• FDA tries to limit to those surrounding
  innovative or unique development situations --
  usually appropriate to discuss
• New chemical entities
• First in class
• Novel mechanism of action or indication
• Situations lacking current guidance
• Fast Track, Accelerated, Orphan Drug Designations
• Regulatory mechanisms e.g., 505(b)(2)
• Problematic pharm/tox signals
• Serious or life threatening disease target
• New sponsor or new to area of drug development
• Significant sponsor questions

58
The Pre-IND Meeting

• Ensure appropriateness and adequacy of
  pre-clinical studies to support proposed clinical
• Submission formats
• Electronic
• Common technical document (CTD)

59
The Pre-IND Meeting Meeting Package

• Detail on product and product characteristics
• Proposed clinical trials
• API, raw materials, components, grades, and
  release specifications
• Summary of manufacturing process
• Narrative, flow chart, contamination control
• in-process controls and specs
• final product specs
• ? -- be careful to not box yourself in here

60
The Pre-IND Meeting Meeting Package

• Summary of preclinical data
• Summary of previous human experience
• Questions by discipline, focusing on
• PK/PD
• ADME
• Dosing
• Manufacturing (CMC)
• Clinical development plan

61
The Pre-IND Meeting Some FDA Hotpoints

• Chemistry (CMC)
• Dont skimp on information
• Note if CMC issues are very numerous, FDA
  guidance contemplates ability for a separate
  meeting on those
• See IND Meetings for Human Drugs and Biologics
  -- Chemistry, Manufacturing and Controls
  Information, May 2001. http//www.fda.gov/cber/gd
  lns/ind052501.pdf
• State your IND will comply with CMC expectations
  in the two IND guidances
• Content and Format of IND application for Phase 1
  Studies of Drugs
• INDs for Phase 2 and Phase 3 Studies CMC
  Information

62
The Pre-IND Meeting Some FDA Hotpoints The CMC

• Discuss
• Physical, chemical and/or biological
  characteristics
• Manufacturers
• Source and method of preparation
• Removal of toxic reagents
• Quality Controls (identity, assay, purity,
  impurities profile)
• Formulation
• Sterility (e.g., aseptic, release, endotoxin
  testing)
• Linkage of pharm/tox batches to clinical trial
  batches
• Stability
• Drug delivery systems (if non-conventional)

63
The Pre-IND Meeting Some FDA Hotpoints CMC

• Biologics CMC
• include characterization of master and working
  cell banks
• Human source drugs
• donor screening
• Removal of adventitious agents
• Potency assay
• Source, country of origin of animal derived
  materials
• Immunogenicity assays for
• Comparability physiochem characterization

64
The Pre-IND Meeting Some FDA Hotpoints

• CMC Microbiology address sterility
  considerations for products applied to open
  wounds lesions
• Pharm/Tox
• 505(b)(1) vs. (b)(2) can impact nonclinical
  needs
• Adequately characterize excipients toxicity
• Rationale for starting dose, dose escalation
• ADME data
• Relevance of animal species, including nonhuman
  primates
• Address significant findings e.g., animal deaths

65
The Pre-IND Meeting Some FDA Hotpoints

• Clinical Microbiology
• Must conduct micro studies in accord with recent
  methods and standards
• Include supportive documentation on spectrum of
  activity against targeted pathogens
• Include exposure-antimicrobial activity
  relationship for relevant pathogens
• Have clinical micro questions

66
The Pre-IND Meeting Some FDA Hotpoints

• Clinical
• Avoid seeking EOP2 commitments too early
• Consider use of bridging studies for many
  formulation changes (especially for topicals)
• Heed exposure-response relationships for safety
  and effectiveness
• Volunteers v. target population
• Stopping rules
• Immunogenicity assessment, banked serum

67
The Pre-IND Meeting Some FDA Hotpoints

• General
• Pediatric development plan
• Quality of life assessments
• Dont include new information as updates to
  briefing package
• Sources (1)An FDA Approach to the Pre-IND
  Meeting Between a Sponsor and the Agency.
  Jonathon Wilkin, MD, Director, Division of
  Dermatological and Dental Products, CDER,
  presented at DIA Annual Meeting, 2004.
• (2) The Biological Pre-IND Meeting. Karen D.
  Weiss, M.D., Office of Drug Evaluation VI, CDER,
  presented at DIA Annual Meeting, 2004.

68
End of Phase 1 (EOP1)

• Primarily for Fast Track products
• To discuss Phase 2 controlled trials for drugs
  aimed at life threatening/severely debilitating
  conditions
• Goal agreement on study design including
  statistical plan

69
End of Phase 2A (EOP2A)

• New meeting type is a pilot program
• Usually involves CDER Office of Pharmacology and
  Biopharmaceutics
• Aim exposure-response data
• Impact determines continuance or additional
  Phase 2 trials

70
End of Phase 2 (EOP2)

• Goal discuss and secure agreement on Phase 3
  studies design
• To support indications
• Safety data
• Monitoring requirements
• Pediatric requirements
• Other FDA concerns

71
End of Phase 2 (EOP2)

• Common issues discussed
• Clinical trial design
• Chemistry formulation, stability, impurities
• Unique physicochemical (e.g., polymorphs) and
  biological properties
• Starting material designation
• Dissolution test procedures coordination with
  agency
• for more examples, see pages 6-8 of Guidance on
  IND Meetings, CMC, cited on Slide 61.
• ClinPharm drug interactions, special
  populations, food effects
• PharmTox new findings (if any) from chronic or
  carcinogenicity studies

72
End of Phase Meetings -- Briefing Packages

• Summary of clinical data (safety effectiveness)
• Rationale for additional studies
• Proposed next study(s)
• Detailed description of product and manufacturing
  processes, including
• Changes in formulation, scale, material sources,
  etc.

73
Pre-NDA/BLA Meeting

• To discuss
• Evidence of effectiveness
• Any additional statistical analyses
  needed/requested by FDA
• Need for risk management in indication
• Technical aspects
• Timing 6 to 12 months before anticipated filing
  (per Good Review Management Guidance)

74
Pre-NDA/BLA Meeting

• Before requesting, assess whether application is
  ready to be filed
• All clinical data in and evaluated
• All previous advice implemented or, if not,
  agreed approach to address the issue
• Facility ready for pre-approval inspection
• ready for full scale-up
• Equipment, methods, and processes validated

75
Pre-NDA/BLA Meeting Briefing Package

• Similar to EOP meetings, but with more detailed
  manufacturing info
• Emphasis on any changes and plans for linkage
• Site, synthesis, controls, formulation,
  components, etc.
• Summary of pivotal trials to support NDA/BLA
  approval
• Identify primary endpoints
• Proposed post-marketing risk management plan
• Stability protocol
• Proposed format (e vs. hard copy vs. CTD)

76
Pre-NDA/BLA Meeting Briefing Package

• Contract manufacturer (if applicable) identify
  and justify
• Proposed submission timeline
• Questions
• NDA/BLA contents
• Any unresolved or new issues
• Discuss strengths and weakneses

77
Pre-NDA/BLA Meeting Some FDA Hotpoints

• Viewed as primarily organizational and to discuss
  last minute issues
• Thus, most scientific and potential review issues
  should have been settled already
• ORM Division determines if meeting is discipline
  specific
• Remember this can be key to avoiding a later
  refuse-to-file on the NDA and delays in the
  review cycle

78
Special Protocol Meetings

• Creature of FDAMA -- Implement 119(a)
• Covered studies
• Phase 3 trials to support an effectiveness claim
  if discussed at the EOP2 meeting (or FDA knows
  the developmental context)
• Animal carcinogenicity studies
• also should be discussed at EOP2 meeting
• If not, notify division director 30 days before
  submitting request
• Stability studies
• Request for Assessment required, including the
  protocol
• FDA has 45 days to review sends letter
• If you want a meeting after receiving that
  letter, handled as a Type A meeting

79
PART 4

• TIPS TRAPS

80
Meeting Goals Direct and Indirect

• Educate FDA about product, development and
  clinical efforts, technical expertise
• Facilitate a successful and fast NDA/BLA review
  and approval
• Address agency concerns as early as possible
• Avoid delays due to need to correct or add to
  developmental plans
• Gain FDA buy-in on overall strategy

81
When to Request a Meeting

• Be sure you are ready
• If requested and granted and you cant be ready,
  cancel or reschedule
• Will start cycle over, but you dont want to
  waste agency time

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Questions for Meetings

• Key to process frame with great care
• Avoid overbroad and open-ended questions
• Be specific and answerable (if possible)
• Provide supporting information to allow question
  to be answered (if possible)
• Provide the answer in the question lead the
  witness (if possible)
• Example Does the agency agree that one,
  multi-center study, with separately-analyzable
  data, is sufficient to support approval of the
  indication?

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Meeting Preparation Essential!!

• Know the Briefing Package cold (as many folks as
  possible should do this)
• Know relevant statutes, regulations and guidance
• Know your product and its capabilities and faults
• Rehearse more than once, if possible
• Use a pre-meeting team to play the FDA roles
  (hire outside consultants if needed)
• Night before get hotel close to FDA (D.C. area
  traffic is terrible)

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Meeting Preparation Essential

• Prepare for alternative approaches and fallback
  positions in advance
• Define roles
• Company lead (often R.A.)
• Role of CEO usually to listen unless has
  substantive expertise (e.g., in small start-ups)
• Subject matter experts must stick to their
  areas
• Scribe dedicated solely to taking notes, with
  stress on
• FDA questions
• FDA recommendations

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Meeting Preparation Essential

• Be persuasive, but open honest
• Do not speculate
• Do not hide information the last thing you want
  is for FDA to find out about a negative issue
• Be succinct no dog and pony shows
• Focus on QA
• Do not interrupt
• Watch your humor

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Meeting Preparation Essential

• Dont promise anything that you are not prepared
  to do
• Acknowledge the issue
• defer if needed take it into consideration
• Dont include any off-agenda items avoid
  surprise
• Dont bring anyone not on the list (e.g., an
  attorney)
• Dont debate policy -- unless it is clearly on
  the agenda and has been briefed rarely will
  be addressed in these types of meetings

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After the Meeting

• Debrief ASAP
• ? -- if public company, assess immediately if any
  SEC disclosure duties implicated by meeting
• Prepare your minutes ASAP and route internally
• get to FDA Project Manager ASAP (within 7 days)
• Review and address FDA minutes (as discussed
  previously)
• Correction requests should be based on
  significant differences in understanding
• disagreements are usually bound for dispute
  resolution mechanisms

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Causes of Unsuccessful Meetings

• Inadequate planning and coordination
• Poor preparation
• Incomplete or inadequate information
• Confrontations
• Poor communication
• Not providing all relevant information
• Lack of candor
• Poor questions

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Causes of Unsuccessful Meetings

• Stressing commercial or corporate concerns over
  science
• Failure to follow up on action items or advice,
  even if not in formal minutes (but try to get it
  in there)
• Not adequately documenting agreements, decisions,
  commitments
• By-passing chain of command

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PART 5

• Q A

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Questions?

• Write, call, fax or e-mail

92
About your instructor

• Michael A. Swit has over 20 years of experience
  addressing critical FDA legal and regulatory
  issues. His vast and varied experience, which he
  is now providing as a solo practitioner, includes
  serving for three and a half years as vice
  president and general counsel of Pharmaceutical
  Resources, Inc. (PRI) a prominent generic drug
  manufacturer through its Par Pharmaceutical
  subsidiary. He thus also brings an industry and
  commercial perspective to his representation of
  FDA-regulated companies and, to that, effect also
  counsels on an array of transactional issues
  relating to FDA-regulated biomedical industry,
  including clinical research agreements, mergers
  acquisitions, contract manufacturing, and due
  diligence inquiries.
• While at PRI from 1990 to late 1993, Mr. Swit
  spearheaded the companys defense of multiple
  grand jury investigations, other federal and
  state proceedings, and securities litigation
  stemming from the acts of prior management. Mr.
  Swit then served from 1994 to 1998 as CEO of
  Washington Business Information, Inc. (WBII) a
  premier publisher of FDA regulatory newsletters
  and other specialty information products for the
  FDA-regulated community. From May 2001 to May
  2003, Mr. Swit was special counsel in the FDA Law
  Practice Group in the San Diego office of Heller
  Ehrman White McAuliffe. Before that, he was
  twice in private practice with McKenna Cuneo,
  from 1988 to 1990 and, most recently, from 1999
  to 2001, first in that firms D.C. office and
  most recently, in its San Diego office. He first
  practiced FDA regulatory law with the D.C. office
  of Burditt Radzius from 1984 to 1988. Mr.
  Swit has taught and written on a wide variety of
  subjects relating to FDA law including, since
  1989, co-directing a three-day intensive course
  on the generic drug approval process and editing
  a guide to the generic drug approval process,
  Getting Your Generic Drug Approved. He is a
  member of the California, Virginia and District
  of Columbia bars.

93
Acknowledgements

• The speaker gratefully acknowledges the help of
  Dan Klassen of Parexel whose recent presentation
  before the San Diego Regulatory Affairs Network
  (SDRAN) formed the basis for parts of this
  presentation.