THE LAW OFFICES OF MICHAEL A. SWIT 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

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

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

Part 1 The “Law” of Meetings

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

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

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” – “…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 …

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.”

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

The rest is commentary … 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 Ever notice that's Groundhog Day? Rabbi Akiva -- while standing on one foot

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.

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.

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--

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.

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.

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.

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....

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.

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]

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.

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.

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 life-threatening or severely debilitating illnesses, sponsors may request to meet with FDA-reviewing officials early in the drug development process…

FDA’s Guidances, etc., and The Handling of FDA Meetings Part 2 FDA’s Guidances, etc., and The Handling of FDA Meetings

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

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

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

“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.”

“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

“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 FDA’s evaluation of protocols submitted via assessment letters

“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

“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)

“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

“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

“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

“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

“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)

“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

“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)

“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)

“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

“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

“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

“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

“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)

Failure to timely submit – FDA may postpone or cancel “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

“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)

“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)

List of specific questions by discipline “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

“Formal Meeting” Guidance – Requesting Procedures – The “Information Package” … 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

“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

“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.”

“Formal Meeting” Guidance – Documentation of Meeting Minutes – summarize, in bulleted form: Important discussion points Decisions Recommendations Agreements Disagreements Issues for further discussion Action items

“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

“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

THE DIFFERENT MEETINGS Part 3 THE DIFFERENT MEETINGS

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

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

The Pre-IND Meeting … Ensure appropriateness and adequacy of pre-clinical studies to support proposed clinical Submission formats Electronic Common technical document (CTD)

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

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

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

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)

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

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

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

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

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.

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

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

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

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

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.

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)

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

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)

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

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

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

PART 4 TIPS & TRAPS

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

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

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?”

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)

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

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

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

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

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

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

PART 5 Q & A

Michael A. Swit, Esq. FDACounsel.com 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

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.

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.