PMI Dutch Chapter Meeting 22 Feb 2011

1. FDA Advisory Committee Meeting:The management of an acceptance test for a new medicine by external stakeholders Jan W.C.M JansenGlobal Project DirectorAbbott Healthcare Products Weesp, The Netherlands PMI Dutch Chapter Meeting22 Feb 2011

2. Who is Jan Jansen? • Chemistry/biochemistry University of Utrecht • PhD University of Nijmegen • Philips Duphar (1979)  Solvay Pharmaceuticals  Abbott • Groupleader Vascular BiochemistryResearch Program ManagerGroupleader BiotechnologyGlobal Project Director since April 2000 leading Project Teams, phase I-II-III studies, Advisory Boards, Advisory Committee, etc

3. FDA Advisory Committee Meeting:The management of an acceptance test for a new medicine by external stakeholders AGENDA:- What is an FDA Advisory Committee? - How to manage the preparation for a FDA AC

4. Advisory Committee: focus on safety An Advisory Committee meeting is normally part of the review process of a NCE dossier to obtain registration in US Nowadays for almost every dossier an Advisory Committee is organized due to the increased focus on safety

5. The consequence of submission a dossier for a new drug application in US may be to be invited by FDA for an Advisory Committee meeting This is excellent news: your drug reached the final review stage. One hurdle to go!

6. Advisory Committee The Food and Drug Administration (FDA), to assist in its mission to protect and promote the public health, uses 49 committees and panels to obtain independent expert advice on scientific, technical, and policy matters Advisorycommittees provide FDA with independent opinions and recommendations from outside experts on applications to market new drugs, and on FDA policies.  The marketing applications include data to show the safety and effectiveness of human drugs. The outside experts receive summary information about the applications and copies of  FDA's review of the application documents. Based on this information, advisory committees may recommend approval or disapproval of a drug's marketing application.  FDA generally follows an advisory committee's recommendation, but is not bound to do so. 

7. AC members • Recognized expertstechnically qualified experts in their field and have experience interpreting complex data. Candidates must be able to analyze detailed scientific data and understand its public health significance • Consumera consumer representative must be able to analyze scientific data, understand research design, discuss benefits and risks, and evaluate the safety and efficacy of products under review. It is also essential that the representative have an affiliation with and/or active participation in consumer or community-based organizations • Industry industry representatives act on behalf of regulated industry at committee meetings. The representative discusses an issue before the committee from the perspective of the affected industry and not as an individual from a specific sponsor. Non-voting • Patient representatives

8. AC part of dossier review process Dossier filing FDA messagefor AC Dossiersubmission AC phase IIIclinical studiesseveral years dossier completion6-9 months dossierreview process10—14 months decisionletter

9. What is a dossier? • A dossier consists of 4 main parts: • Preclinical part:reports and overall summaryall preclinical studies (pharmacological, toxicological, ADME) • Pharmaceutical part all required reports on the active ingredient (chemical process) and finished product (pharmaceutical process) • Clinical partall reports (efficacy and safety) and overall summary • (proposed) SPC (EU) or TPI (US)describes the wished indication SmPC: Summary of Product CharacteristicsTPI: Targeted Package Insert

10. AC has a fixed agenda provided by FDA

12. AC meeting room

14. How to prepare for an (naïve) Advisory Committee? the company expects an positive result!

15. Project Team (P-Team) composition (in most companies) All compound knowledge is in this team present

16. Givens at the moment of submission • Project Team (P-Team) - Is responsible for all activities of a certain NCE- Consists of all essential disciples: Clinical, Pharmaceutical, Preclinical, Regulatory Affairs, Marketing, Pharmacovigilance- Reports to Management Governance • Cooperation with CROs- Clinical and Regulatory Affairs- Pharmacovigilance (risk management plan) • No in-house experience on ACs • Between submission and an AC is ca. 12 months FDA message ca. 3 months before AC!!

17. Risk Management Plan

18. First actions Immediately after submission: • Contact US based company (PharmApprove™) “PharmApprove teams are helping to prepare for drug and device teams for upcoming Advisory Committee hearings, providing services including strategy development, medical writing, presentation coaching, slide creation, and project management”. • Compose adequate AC P-Team and Core-Team • Create clear governance interactions

19. US based AC coaching company

20. Essential for AC • How to behave • What to say • How to answer • Which prove/arguments to show • In fact an AC is a media circus • Handling the AC-members is key

21. AC P-Team Global Project Management Clinicial Statistics Clinical Pharmacology CRO Clin Pharm CRO Clin/Reg Affairs Pharmacovigilance CRO Pharmacovigilance Preclinical Toxicology Preclinical Pharmacology Preclinical US Pharmaceutical Dev Reg Affairs Phar Dev US Regulatory Affairs US Marketing Media AC Core-Team Global Project Director Regulatory Affairs US Clinical Marketing P-Team, AC P-Team and AC Core-Team • P-Team • Global Project Director • Clinical • Preclinical Toxicology • Preclinical Pharmacology • Regulatory Affairs (US) • Pharmaceutical Dev • Marketing

22. AC Core P-Team/AC P-Team vs. PharmApprove AC Core P-Team organization PharmApproveAC preparation experience Weekly telecons AC P-Team Delivery of:-knowledge Delivery of:-planning-training-messaging -kick off- f-t-f meetings- weekly telecons- ad hoc telecons

23. Interaction with Governance Bodies Executive Committee decides on strategy Portfolio Committee Decides on running activitiesProposals for strategy DirectinvolvementACpreparations Frequentlyaspresenter P-Teamoperational team Decides on executionProposals for planInvolved in strategy

24. First key step: KICK-OFF meetingasap after submission f-t-f ALL members present

25. AT Kick-off: Roles and Responsibilities • Presenters: -Introduction -Unmet medical need -Clinical facts -Risk Management Plan -Risk-benefit -Conclusions -Question handling • Who in bullpen for answers • Who instructs slide company for slide projection • Who is preparing what • Who interacts with PharmaApprove, Governance Bodies, etc

26. Preparation Plan • Phase A:Period: Feb-JunePrepare for Mock Panel 1Goals:- slide sets- briefing book- presentations- organize mock panel 1 • Phase B:Wait for message from FDAIn case invitation for AC  full program towards AC (period 3 months)Goals:- optimized slide sets- final briefing book (ready 2 months before AC)- 2 extra mock panels- additional Q&A training- messaging

27. Plan A: preparation until FDA call December: dossier submission January: f-t-f contact with PharmApprove February: kick off meeting March: key messages April: draft Briefing Book ready May: slide sets ready June: Mock panel 1 FDA call

28. Conclusions after Mock Panel 1

29. Plan B: preparation from FDA call until AC September: - FDA call - restart kick off October: - mock panel 2 - update Q&A - verbal comments FDA on dossier (end Oct) November: - early Nov: BB to FDA - mid Nov: mock panel 3 - key messages ready November (end): - slide sets final/ Q&A ready - know the FDA panel - media plan Dec (week 1): - comments FDA (FDA BB)/ adapt presentations if necessary - presentation/answer coaching - adapt slides/ incorporate in Q&A Dec (week 2): - adapted slide sets ready Dec (week 2.5): AC

30. Conclusions after Mock Panel 2

31. Conclusions after Mock Panel 3

32. Between Mock-Panel 3 and AC …. • Analyse FDA Briefing Book contains FDA comments on your dossier - adapt Q&A - incorporate in slide set • Analyse members AC - what’s their specialism? - what type of questions did they ask previously? - How do they behave, formulate questions? • Q&A: rehearse, ………

33. The AC meeting • Exciting  everyone knows “you have one chance” • Self-reliance is key • Correction not possibleIt’s like a soccer team which starts to play the match you hope they act according your instructions • Voting after 9 hours • It is an advice but difficult to change!

34. Overall conclusions • To be invited for AC is the route for success! • Start as soon as possible: always too less time! • Be clear and fair from start to finish • Don’t focus on costs but on quality! • It is a US event!Don’t think you can do the job with Europeans only • US KOLs are essential • Focus on AC only for last 4 months (no other activities) • Believe in your product and show this! • Stay quiet, be relaxed and convinced.

35. Thank you!

36. Q&A grid Slide Content Area : Slide Content Manager:

37. Know your AC members: complete CV

38. AC meeting room FDA FDA AC members AC members presenter Audienceca. 100 seats AC members screen Slide deck company expertsmax 15 persons