# Presentation: 195613

## Cooperation in the Development of a Risk Management Program 

- Mary Willy, PhD
- June 15, 2004

## Outline

- Background
- Initial steps in review of RMP
- Communication with relevant CDER offices
- Coordination of comments
- Communication with sponsor
- Finalizing the plan
- Conclusions

## Office of Drug Safety (ODS) Organization

- Division of Drug Risk Evaluation (DDRE)
- Division of Surveillance, Research and Communication Support (DSRCS)
- Division of Medication Errors and Technical Support (DMETS)

## PDUFA III approved October 2002
formalized FDA role in risk management 
PDUFA III called for FDA to develop three interrelated guidances on risk management topics 
Premarketing Risk Assessment 
Pharmacovigilance/ pharmacoepidemiology
Risk Management per se

- PDUFA III approved October 2002
- formalized FDA role in risk management
- PDUFA III called for FDA to develop three interrelated guidances on risk management topics
- Premarketing Risk Assessment
- Pharmacovigilance/ pharmacoepidemiology
- Risk Management *per se*

## Review pre-NDA packages
Participate in pre-NDA meetings with industry: preliminary discussion about the need for risk management
Review of proposed RMP in NDA
Review implementation of RMP

- Review pre-NDA packages
- Participate in pre-NDA meetings with industry: preliminary discussion about the need for risk management
- Review of proposed RMP in NDA
- Review implementation of RMP

## 41 Sponsor-submitted plans reviewed in 2003 and 2004
Highly variable in content and format
Desired elements not always present
Without articulated goals for plan
Unnecessary RMP submitted in some cases

- 41 Sponsor-submitted plans reviewed in 2003 and 2004
- Highly variable in content and format
- Desired elements not always present
- Without articulated goals for plan
- Unnecessary RMP submitted in some cases

## ODS working with Office of New Drugs (OND) to review submitted plans
Developing procedures and best practices for appropriate review of RMP (drafting CDER MaPP)

- ODS working with Office of New Drugs (OND) to review submitted plans
- Developing procedures and best practices for appropriate review of RMP (drafting CDER MaPP)

## Initial steps in RMP process - 1

- Safety concern is identified
- Evidence from animal studies
- Evidence from clinical trials
- Evidence from other drugs in the class
- Evidence from post-marketing

## Initial steps in RMP process - 2

- Sponsor submits a plan to manage the risk
- Included in part of original submission
- Section depends on format of submission
- Submitted as separate document
- May be requested by FDA if safety issue identified during NDA review or postmarketing

## ODS meets with Office of New Drugs (OND) Division - 1 

- ODS team representing DDRE, DSRCS, and DMETS meets with OND Division
- OND Division provides background on NDA
- Indication, anticipated users, safety concerns

## ODS meets with Office of New Drugs (OND) Division - 2 

- ODS team explores with OND
- Are all the important safety concerns identified in the proposed RMP?
- Are the proposed risk management components reasonable to the Review Division?
- Introduce and explore other possible options

## Follow-up ODS Team Meeting - 1

- Following discussion with OND, ODS multidisciplinary team is identified
- Team leaders from each ODS division designate individuals who will contribute to review

## Follow-up ODS Team Meeting - 2

- Follow-up meeting with ODS team to discuss assignment of sections of RMP
- Sections of plan assigned to relevant persons
- Coordinator identified
- Timeline developed
- Special concerns discussed
- Other offices that might need to participate listed, such as Controlled Substances Staff (CSS)

## ODS Divisions Review Roles

- DDRE – epidemiological studies, AE reporting plan, active surveillance, evaluation plan
- DMETS – trade name, medication errors, carton container labeling
- DSRCS – patient and healthcare practitioner education, drug utilization monitoring plan, active surveillance, evaluation plan of RMP tools

## Draft ODS Response to Submission

- Project coordinator incorporates the 3 ODS divisional perspectives into a cohesive response
- Divisions asked to review materials and submit comments to team leaders
- Coordinator takes drafts from divisions and prepares final document for sign off

## ODS Reconvenes with Review Division

- ODS provides comments and rationale
- Discussion and action plan developed
- List of concerns, if any, identified
- Plan for next steps
- Written response to sponsor
- Take to upper CDER management (regulatory briefing)
- Need for further information from ODS or OND

## Sponsor Communication  

- OND provides feedback to sponsor
- Sponsor may request telecon or face-to-face meeting
- ODS participates in meetings when needed

## Next Steps

- Depending on the extent of revision requested there may be numerous meetings required
- Often short time frames for comment and review
- Often many internal follow-up meetings are needed
- Difficult to arrange with full calendars for team members

## Challenges 

- Challenge is coordinating 3 division comments
- Communicating comments to relevant parties within ODS and outside ODS
- May need to involve other divisions too
- Office of Compliance, Division of Drug Marketing, Advertising and Communication, and General Counsel

## Final Agreement

- OND Division communicates final changes that have been accepted
- Final time frame for implementation communicated

## Conclusions - 1

- RMP review by CDER is often a very lengthy process that can take 6 months or more
- Sponsors need to get their plans in early
- Develop their plans adequately with clear goals

## Conclusions - 2

- The number of different individuals involved makes the process very challenging
- As CDER and sponsors gain more experience the review of RMP will become more routine for everyone