fda advisory committee meeting: the management of an acceptance test for a new medicine by external...

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 ProductsWeesp, The Netherlands

PMI Dutch Chapter Meeting22 Feb 2011

PMI Dutch Chapter22 Feb 2011

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Who is Jan Jansen?

• Chemistry/biochemistry University of Utrecht

• PhD University of Nijmegen

• Philips Duphar (1979) Solvay Pharmaceuticals Abbott

• Groupleader Vascular Biochemistry

Research Program Manager

Groupleader Biotechnology

Global Project Director since April 2000

leading Project Teams, phase I-II-III studies, Advisory Boards, Advisory Committee, etc


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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


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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


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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!


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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

Advisory committees provide FDA with independent opinionsand recommendations from outside experts on applicationsto 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 aboutthe applications and copies of FDA's review of the application documents.Based on this information, advisory committees may recommendapproval or disapproval of a drug's marketing application. FDA generally follows an advisory committee's recommendation, but is not bound to do so.


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AC members•Recognized experts

technically qualified experts in their field and have experienceinterpreting 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 withand/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 perspectiveof the affected industry and not as an individual from a specific sponsor. Non-voting

•Patient representatives


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AC part of dossier review process

phase IIIclinical studies

several years

dossier completion

6-9 months

Dossiersubmission

Dossier filing

FDA messagefor AC AC

decisionletter

dossierreview process

10—14 months


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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


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AC has a fixed agenda

provided by FDA


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AC meeting room


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How to prepare for an (naïve) Advisory Committee?

the company expects an positive result!


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Project Team (P-Team) composition (in most companies)

All compound knowledge

is in this team present


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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!!


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Risk Management Plan Risk Response Response tactics

never tasted the atmosphere

avoid visit an AC at early stage

preparation time too short when waiting for FDA message

avoid start asap after dossier submission

no in house experience with AC

avoid approach a company which is experienced

due to focus on content, no time for organization

transfer idem

due to unknown questions, a lot of slides to be prepared

transfer approach a slide company

in house know-how may be insufficient

accept in house knowledge is far more then external

no adequate well known US clinical expert to assist

avoid select and invite


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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


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US based AC coaching company


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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


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P-Team, AC P-Team and AC Core-Team

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

• Global Project Director

• Clinical

• Preclinical Toxicology

• Preclinical Pharmacology

• Regulatory Affairs (US)

• Pharmaceutical Dev

• Marketing


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AC Core P-Team/AC P-Team vs. PharmApprove

AC Core P-Team

PharmApproveAC preparation experience

Delivery of:-planning-training-messaging

Delivery of:-knowledge

-kick off- f-t-f meetings

- weekly telecons- ad hoc telecons

organization

AC P-Team

Weekly telecons


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Interaction with Governance Bodies

Executive Committee

decides on strategy

Portfolio Committee

Decides on running activitiesProposals for strategy

P-Teamoperational team

Decides on executionProposals for plan

Involved in strategy

Directinvolvement

ACpreparations

Frequentlyas

presenter


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First key step: KICK-OFF meetingasap after submission

f-t-f ALL members present


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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


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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


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Plan A: preparation until FDA call

December: dossier submission

June: Mock panel 1

January: f-t-f contact with PharmApprove

February: kick off meeting

April: draft Briefing Book ready

March: key messages

May: slide sets ready

FDA call


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Conclusions after Mock Panel 1

Panel: 3 clinical experts, 1 statistician, 1 risk management consultant

adequate panel

Briefing Book too long, to much details decision: rewrite immediately

Presentations too detailed action: focus on messaging

Slides for first round okay; action: be sure to have all aspects covered; more structure required

Key messages too much science action: one-liners

Q&A too detailed action: training


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Plan B: preparation from FDA call until AC

September: - FDA call- restart kick off

Dec (week 2.5): AC

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

Dec (week 1): - comments FDA (FDA BB)/ adapt presentations if necessary- presentation/answer coaching- adapt slides/ incorporate in Q&A

November (end): - slide sets final/ Q&A ready- know the FDA panel- media plan

Dec (week 2): - adapted slide sets ready


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new adequate panel

Briefing book rewritten: okay, some adaptations

Presentations better however still too detailed; improve messaging

Slides prepare modules

Key messages better; less science

Q&A think out of the box


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new adequate panel

Briefing book okay (was submitted to FDA early Nov)

Presentations okay

Slides okay action: update slide book

Key messages okay

Q&A rehearse, rehearse ….


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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, ………


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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!


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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.

Thank you!


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Slide Content Area :Slide Content Manager:

Q # Category Issue / Question area Response Responder Slides

Q&A grid


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Know your AC members: complete CV


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AC meeting room

company expertsmax 15 persons

Slide deck

screen

FDAA

C m

embe

rs

AC membersA

C m

embers

Audienceca. 100 seats

presenter

FDA

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