SUCCESSFUL FDA MEETINGS
DIA West Coast Drug Development Conference
San 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: 760-454-2979
mswit@fdacounsel.com
www.FDACounsel.com
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Overview of Tutorial
Part 1 -- The “Law” of Meetings
 Part 2 – FDA’s Guidances, etc., on FDA
Meetings
 Part 3 – Details on the Different Types of
Meetings
 Part 4 – Tips and Traps
 Part 5 – Q & A

FDACounsel.com
2
What We’re 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
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3
Part 1
The “Law” of Meetings
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4
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
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5
Where to Go for Perspective –
or What is the Law Governing FDA
Meetings?

FDA advisory opinions – formal
position of FDA; binding until refuted;
FDA can’t 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
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6
Where to Go for Perspective –
or What is the Law Governing FDA
Meetings?

What’s not “law”?


Anything else FDA writes – guidances,
speeches, warning letters, complaints in Federal
court –
“Guidance” –



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“…describes the agency’s 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 …
7
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.”
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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:


FDACounsel.com
Statutes – but only rarely
Regulation – but only in fairly general terms – 21 CFR
10.65
9
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
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10
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 can’t change its mind unless
there’s new safety/effective data”
clauses.
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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.
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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-FDACounsel.com
13
Section 505(b)(4)(C) …
(i)
(ii)
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.
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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.
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15
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.
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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....
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17
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.
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18
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]
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19
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 FDA`s discretion.
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20
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.
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21
FDA Regulations on Meetings
…

IND Regulations – 21 CFR Part 312


312.47 -- Meetings
(a) General. Meetings between a sponsor and
the agency are frequently useful…during the
course of a clinical investigation.
312.82 Early consultation
For products intended to treat lifethreatening or severely debilitating illnesses,
sponsors may request to meet with FDAreviewing officials early in the drug
development process…
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Part 2
FDA’s Guidances, etc., and
The Handling of FDA
Meetings
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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 CDER’s External
Constituents.” CDER, March 1996.
http://www.fda.gov/cder/mapp/4512-1.pdf
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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.
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http://www.fda.gov/cder/mapp/4151-1.pdf
25
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/4150.1.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
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“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.”
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“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
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“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:



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Dispute resolution meetings
Clinical hold discussions
Special protocol assessment meetings requested by
sponsors after FDA’s evaluation of protocols submitted
via assessment letters
29
“Formal Meeting” Guidance –
Types of Meetings – “A” …

Scheduling of Type A meeting:


Within 30 days of FDA’s receipt of a
written request or
If sponsor requests a later date, within 14
days of the requested date
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“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
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(21 CFR 312.47)
31
“Formal Meeting” Guidance –
Types of Meetings – “B” …

Scheduling of Type B meeting:


Within 60 days of FDA’s receipt of a
written request or
If sponsor requests a later date, within 14
days of the requested date
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“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
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“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:


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Advertising, except pre-launch activities
Post marketing safety evaluation meetings
34
“Formal Meeting” Guidance –
Types of Meetings – “C’ …

Scheduling of Type C meeting:


Within 75 days of FDA’s receipt of a
written request or
If sponsor requests a later date, within 14
days of the requested date
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35
“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)
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“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
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“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)
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“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)
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“Formal Meeting” Guidance –
Requesting Procedures … Contents
of Request Letter …

Specifically …

Draft list of questions, by discipline








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Chemistry
CMC & Microbiology (if applicable)
Pharm/Tox
Clinical Pharmacology & Biopharmaceutics
Clinical Microbiology
Clinical
Biostatistics
Administrative & Regulatory
40
“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 documentation 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
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“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
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“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
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“Formal Meeting” Guidance –
Requesting Procedures – The
“Information Package”
“FDA’s 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)
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“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
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“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)
(continued)
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“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)
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“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
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“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
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“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

Action items





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here, but is to be included in minutes)
50
“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.”
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“Formal Meeting” Guidance –
Documentation of Meeting

Minutes – summarize, in bulleted form:







Important discussion points
Decisions
Recommendations
Agreements
Disagreements
Issues for further discussion
Action items
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“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 won’t comment on sponsor’s draft
… unless it reflects major differences in view of
meeting’s outcomes
If major differences identified, sponsor should
raise these with the review division initially
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“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 head’s up you’re pursuing this

Project manager issues response in writing


Changes agreed to by FDA – an addendum
Sponsor – if still not happy, pursue dispute
resolution
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54
Part 3
THE DIFFERENT
MEETINGS
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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
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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
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The Pre-IND Meeting …


Ensure appropriateness and adequacy
of pre-clinical studies to support
proposed clinical
Submission formats


Electronic
Common technical document (CTD)
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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
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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
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The Pre-IND Meeting – Some
FDA Hotpoints

Chemistry (CMC)
 Don’t 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/gdlns/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
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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)
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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
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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
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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
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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
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The Pre-IND Meeting – Some
FDA Hotpoints …

General



Pediatric development plan
Quality of life assessments
Don’t 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.
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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
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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
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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
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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
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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.
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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)
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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


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ready for full scale-up
Equipment, methods, and processes validated
74
Pre-NDA/BLA Meeting – Briefing
Package

Similar to EOP meetings, but with more detailed
manufacturing info

Emphasis on any changes and plans for “linkage”


Summary of pivotal trials to support NDA/BLA
approval




Site, synthesis, controls, formulation, components, etc.
Identify primary endpoints
Proposed post-marketing risk management plan
Stability protocol
Proposed format (e vs. hard copy vs. CTD)
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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
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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
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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
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PART 4
TIPS & TRAPS
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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
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When to Request a
Meeting


Be sure you are ready
If requested and granted and you
can’t be ready, cancel or
reschedule

Will start cycle over, but you don’t 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, multicenter 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:


FDACounsel.com
FDA questions
FDA recommendations
84
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 Q&A
Do not interrupt
Watch your humor
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Meeting Preparation –
Essential …

Don’t promise anything that you are not
prepared to do –





Acknowledge the issue
defer if needed – “…take it into consideration”
Don’t include any off-agenda items – avoid
surprise
Don’t bring anyone not on the list (e.g., an
attorney)
Don’t 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:
Michael A. Swit, Esq.
FDACounsel.com
THE LAW OFFICES OF MICHAEL A. SWIT
539 Samuel Ct., Suite 229
Encinitas, CA 92024
office: 760-815-4762 ♦ fax: 760-454-2979
mswit@fdacounsel.com
www.FDACounsel.com
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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 company’s 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 firm’s 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.
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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.
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