Transcript How to manage an AC - PMI Netherlands Chapter

FDA Advisory Committee Meeting:
The management of an acceptance test for a
new medicine by external stakeholders
Jan W.C.M Jansen
Global Project Director
Abbott Healthcare Products
Weesp, The Netherlands
PMI Dutch Chapter Meeting
22 Feb 2011
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 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.
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AC members
•Recognized experts
technically 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
•Consumer
a 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
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AC part of dossier review process
Dossier
filing
FDA message
for AC
Dossier
submission
phase III
clinical studies
dossier
completion
dossier
review process
several years
6-9 months
10—14 months
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AC
decision
letter
What is a dossier?
• A dossier consists of 4 main parts:
• Preclinical part:
reports and overall summary
all preclinical studies (pharmacological, toxicological, ADME)
• Pharmaceutical part
all required reports on the active ingredient (chemical process)
and finished product (pharmaceutical process)
• Clinical part
all reports (efficacy and safety) and overall summary
• (proposed) SPC (EU) or TPI (US)
describes the wished indication
SmPC: Summary of Product Characteristics
TPI: 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
preparation time too short
when waiting for FDA
message
no in house experience with
AC
due to focus on content,
no time for organization
due to unknown questions,
a lot of slides to be prepared
in house know-how may be
insufficient
no adequate well known
US clinical expert to assist
avoid
visit an AC at early stage
avoid
start asap after dossier submission
avoid
transfer
approach a company which is
experienced
idem
transfer
approach a slide company
accept
in house knowledge is far more
then external
select and invite
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avoid
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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
AC Core-Team
•
CRO Clin/Reg Affairs
•
Global Project Director
•
Pharmacovigilance
•
Regulatory Affairs US
•
CRO Pharmacovigilance
•
Clinical
•
Preclinical Toxicology
•
Marketing
•
Preclinical Pharmacology
•
Preclinical US
•
Pharmaceutical Dev
•
Reg Affairs Phar Dev US
•
Regulatory Affairs US
•
Marketing
•
Media
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
organization
PharmApprove
Weekly telecons
AC preparation experience
AC P-Team
Delivery of:
-knowledge
-kick off
- f-t-f meetings
- weekly telecons
- ad hoc telecons
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Delivery of:
-planning
-training
-messaging
Interaction with Governance Bodies
Executive Committee
decides on strategy
Portfolio Committee
Decides on running activities
Proposals for strategy
P-Team
operational team
Decides on execution
Proposals for plan
Involved in strategy
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Direct
involvement
AC
preparations
Frequently
as
presenter
First key step: KICK-OFF meeting
asap 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-June
Prepare for Mock Panel 1
Goals:
- slide sets
- briefing book
- presentations
- organize mock panel 1
• Phase B:
Wait for message from FDA
In 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
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
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Conclusions after Mock Panel 1
Panel:
3 clinical experts, 1 statistician,
1 risk management consultant
Briefing Book
adequate panel
Presentations
too detailed
action: focus on messaging
Slides
for first round okay;
action: be sure to have all aspects
covered; more structure required
too much science
action: one-liners
too detailed
action: training
Key messages
Q&A
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too long, to much details
decision: rewrite immediately
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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
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Conclusions after Mock Panel 2
Panel:
3 clinical experts, 1 statistician,
1 risk management consultant
Briefing book
new adequate panel
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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rewritten: okay, some adaptations
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Conclusions after Mock Panel 3
Panel:
4 clinical experts, 1 statistician,
1 risk management consultant
Briefing book
new adequate panel
Presentations
okay
Slides
okay
action: update slide book
Key messages
okay
Q&A
rehearse, rehearse ….
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okay
(was submitted to FDA early Nov)
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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 possible
It’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.
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Thank you!
Q&A grid
Slide Content Area :
Slide Content Manager:
Q#
Category
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Issue / Question area
Response
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Responder
Slides
Know your AC members: complete CV
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AC meeting room
FDA
screen
AC members
presenter
AC members
FDA
Audience
ca. 100 seats
AC members
Slide deck
company experts
max 15 persons
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