CDER Drug Safety Oversight Board

Douglas C. Throckmorton, M.D.Deputy Director, CDERFood and Drug AdministrationNovember 5, 2005

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

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

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 FDA’s website to healthcare professionals and patients

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

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 drug’s

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

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

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

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)

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

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

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.

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

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

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

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

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

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

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

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

douglas.throckmorton@fda.gov 301-594-5400

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?

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 drug’s 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