CDER Drug Safety Oversight Board

1
CDER Drug Safety Oversight Board

• Douglas C. Throckmorton, M.D.
• Deputy Director, CDER
• Food and Drug Administration
• November 5, 2005

2
Outline

• Drug Safety Oversight Board (DSOB, Board)
  membership and charge
• Summary of Board meetings
• Topics discussed
• Challenges for the Board
• Ongoing assessments of Board function and activity

3
DSOB Membership

• Chair Deputy Director, CDER
• Executive Director Susan Cummins, MD, MPH
• Membership - representatives from CDER offices,
  CBER, CDRH, NIH, VAH
• Consumer or patient representatives and advisory
  committee members as consultants

4
DSOB Charge

• Will provide independent oversight and advice to
  the CDER Center Director on management of
• Important drug safety issues and policies
• Dissemination of certain safety information
  through FDAs website to healthcare professionals
  and patients

5
DSOB Activities (from MaPP)

• Identify, track and oversee management of
  important drug safety issues
• Adjudicated organizational disputes concerning
  management of drug safety issues
• Select drugs to be placed on Drug Watch and
  update their status as appropriate
• Establish policies regarding management of drug
  safety issues in CDER

6
DSOB Activities (from MaPP) (cont)

• Oversee the development of patient and
  professional information sheets in CDER
• Track important emerging safety issues and ensure
  they are resolved in a timely manner
• Ensure CDER decisions about a drugs safety
  benefit from the input and perspective or experts
  within and outside FDA who have not conducted the
  primary review or served as a deciding official
  in the ongoing pre-market evaluation or
  post-market surveillance activities with respect
  to the drug

7
DSOB Staff

• Mary Mease, RPh, MPH
• Toni Marie Nearing-Crowley
• Lee Zwanziger, PhD
• Work with the CDER Divisions to write the Public
  Health Advisories, and write the Patient and
  Professionals Information Sheets

8
Themes from the Four DSOB Meetings to Date

• Didactic sessions on drug safety
• Oversight of CDER safety issues
• Pre-decisional
• Make recommendations for ongoing CDER activities
• Post-decisional
• Review of decisions about safety communications
• Policy development
• Discussion today limited by commercial
  confidential nature of the data used in many of
  the discussions

9
Didactic Sessions

• Familiarize members from outside CDER with
  extensive safety activities ongoing in CDER
• Sessions on
• Detection, assessment and management of safety
  issues in Office of Drug Safety (ODS) and Office
  of New Drugs (OND)
• Newly-issued Guidances related to safety
• Guidance on risk management programs (ODS)

10
Oversight of CDER Safety Issues Predecisional

• Intent
• Provide full picture of the data as we know it
• Extensive background data in advance
• Presentations by knowledgeable CDER review staff
• Solicit specific suggestions for actions
• Reality
• Many safety issues are time-sensitive
• May limit DSOB role here to complex, evolving
  issues
• Board has asked for fuller discussion of ongoing
  work in the Center about safety

11
Predecisional Oversight of CDER Safety Issues
Transdermal Patches Containing Fentanyl

• Issue ODS report of patient deaths and possible
  fentanyl overdoses when using patch
• CDER Actions
• Review of safety data
• Initial evaluation of manufacturing and
  pharmacokinetic data for sources of variability
• Patient/ HCP sheets highlighting need to follow
  label carefully
• Issue for Board
• Additional Risk Management

12
FDA ALERT 7/2005 Narcotic Overdose and Death 
FDA is looking into reports of death and other
serious side effects from overdoses of the
narcotic fentanyl in patients using the fentanyl
transdermal skin patches for pain control.
Directions for using the fentanyl skin patch
must be followed exactly to prevent death or
other severe side effects that can happen from
using too much (overdosing) fentanyl. These
directions are provided in the patient package
insert.
13
Predecisional Oversight of CDER Safety Issues
Transdermal Patches Containing Fentanyl (cont)

• Board Recommendation
• Need to more evaluate fully the sources of
  variability of drug delivery for these complex
  drug delivery systems, especially for drugs with
  narrow therapeutic windows
• Risk Management strategies should be developed
  with this evaluation in mind, including the use
  of Medication Guides
• Action Item for CDER
• After evaluation bring issue back to Board for fu
  discussion and questions

14
Oversight of CDER safety issues Postdecisional

• Many of the safety issues time-sensitive
• Post-decisional oversight important part of DSOB
  role
• DSOB meetings include
• Review of all postings on proposed Drug Watch web
  page
• Postings sent to all members via MedWatch
• Each action summarized at meeting
• Members asked about action taken, whether other
  steps need to be considered
• Feedback has been variable, but frank

15
Postdecisional Oversight of CDER Safety Issues
Withdrawal of Palladone

• Issue decision to withdraw palladone from the
  market for dose-dumping in EtOH
• CDER Actions
• Reviewed in vitro and in vivo data on
  dose-dumping
• Discussed alternative therapies, concluded
  withdrawal of product best
• Started evaluation of other products for similar
  effect
• Board Recommendation
• Agreed with appropriateness of withdrawal
• Recommended standard chemistry review of similar
  products prior to approval
• Action Item for CDER
• FU on chemistry review process

16
Policy Discussions

• DSOB and the new forms of safety communication
  (e.g., Patient Information Sheets) are new ways
  for CDER to address safety
• Need to define its role in the larger effort to
  address safety in CDER
• Avoid duplication of efforts

17
Policy Discussions Issues

• Threshold for communication
• When should the DSOB recommend communicating
  publicly about an emerging safety issue?
• Board has identified set of circumstances that
  could influence the need to say something public,
  including
• Gross credibility of data
• Plausibility (model)
• Other relevant data from related drugs
• Severity/reversability of adverse effect
• Public health impact of adverse effect

18
Policy Discussions Issue Challenge for the
Board

• Oversight function of the Board
• What is effective oversight?
• How to conduct effective oversight?
• New group within CDER with unique mix of
  expertise
• Need to conduct oversight over many diverse
  groups in CDER at work on safety
• Need to assure timely implementation of
  recommendation once accepted by Dr. Galson
• First step need to understand breadth of safety
  issues in CDER and how they are handled

19
Policy Discussions Issue Challenge (cont)

• Oversight Function Action Items
• Board review of ways CDER identifies and handles
  safety issues, including canvassing by Board
  staff to understand full scope of safety
  activities
• Complimentary to ongoing safety tracking in CDER
• Board discussion to translate this review into
  clearer vision of how to conduct safety oversight
• Implementation of a Quality Assurance program to
  develop and track metrics of success for the
  Board
• Two meetings have been held
• Look for additional comments at upcoming Part 15
  Hearing

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Summary

• DSOB has broad set of challenges it is tasked
  with managing
• All important
• Providing effective and timely oversight a
  critical task identified by the Board
• Board members are taking their responsibility
  very seriously, and have provided feedback to
  CDER that has
• Added new, fresh voice on safety in CDER
• Changed the tone of the safety discussions in
  CDER
• Changed the approaches taken by CDER on specific
  safety issues

21

• douglas.throckmorton_at_fda.gov
• 301-594-5400

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Question for Science Board

• Based on your understanding of the safety system
  in CDER, how would you prioritize the 7 goals
  identified for the DSOB?

23
Board Activities (from MaPP)

• Identify, track and oversee management of
  important drug safety issues
• Adjudicated organizational disputes concerning
  management of drug safety issues
• Select drugs to be placed on Drug Watch and
  update their status as appropriate
• Establish policies regarding management of drug
  safety issues in CDER
• Oversee the development of patient and
  professional information sheets in CDER
• Track important emerging safety issues and ensure
  they are resolved in a timely manner
• Ensure CDER decisions about a drugs safety
  benefit from the input and perspective or experts
  within and outside FDA who have not conducted the
  primary review or served as a deciding official
  in the ongoing pre-market evaluation or
  post-market surveillance activities with respect
  to the drug