1. Best Corporate Practices in Meeting the FDA’s Safety Reporting Requirements
FDA Regulatory and Compliance Symposium
Presenter: Saundra Beacham, Director, Drug Safety Operations
Actelion Pharmaceuticals US, Inc.

2. Presentation Objectives
Addressing the corporate practices for meeting FDAs Safety Reporting Requirements in the following areas:
Standard Operating Procedures (SOPs) & Guidelines
Training Program
Assessment / Triage of Adverse Events
Evaluation of Labeling
Post-marketing Commitments
Lessons from Regulatory Inspections
26 Jul 2005

3. Standard Operating Procedures (SOPs) & Guidelines
Development of SOPs & Guidelines or Working Instructions
SOPs – broader in scope
Guidelines & Working Instructions – step by step details
Ensure that SOPs are consistent with the regulations
Set realistic expectations
Train colleagues
Ensure SOPs / Guidelines reflect work practices
26 Jul 2005

4. Standard Operating Procedures (SOPs) & Guidelines, cont.
Periodically review SOPs, update as needed
Revise SOP before implementing changes
Have a system in place for revising SOPs
Remove reference for inactive documents
When more frequent review is not needed, SOPs and guidelines should be reviewed on an annual basis.
26 Jul 2005

5. Training Program Develop a Training Program
Training of Colleagues in Department
Permanent and Contract colleagues
CFR, ICH Guidelines
Standard Operating Procedures
Guidelines / Working Instructions
26 Jul 2005

6. Training Program Training of Colleagues in Other Departments
New company employees
Overview of Drug Safety Department and AE reporting
Sales and Marketing colleagues
Procedures designed for Sales colleagues for reporting AE information
AE Collection Form available on company intranet
Distributors
Interface with distributors, provide instructions & form(s) for reporting adverse experience information to company
26 Jul 2005

7. Assessment of Adverse Events
Individual case assessment by Medical Reviewer
Case review of all adverse events upon receipt of information in department.
Evaluation of information from the reporter and company perspectives:
Seriousness criteria
Labeling
Causality / Relationship
Comments and recommendations for follow-up
26 Jul 2005

8. Assessment of Adverse Events
Group assessment by Global Drug Safety (GDS) representatives
GDS representatives meet weekly for case review (physician input required).
Each Drug Safety unit identifies:
Potential expedited cases
Other cases of interest
GDS representatives discuss cases in meeting and make final decisions regarding reporting to which countries and regulatory agencies.
26 Jul 2005

9. Evaluation of Labeling
Determine whether the adverse event is labeled or listed in the labeling documents
An event is unlabeled when the event term is more specific or more severe than what’s indicated in the label.
When an event is associated with a patient death, then the event is unlabeled unless the labeling document indicates fatalities are associated with the event.
An event is unlabeled when its only reference is in class labeling.
26 Jul 2005

10. Evaluation of Labeling
Create Labeling Conventions to assist in determination of labeling. Here are a few examples, document:
Interpretations in labeling, e.g.
Anemia is labeled, yet anemia w/blood transfusion is not labeled.
Weight gain is labeled, but weight gain greater than 20% is not labeled.
How Lack of Efficacy will be handled
How labeling will be handled when drug use is off-label.
26 Jul 2005

11. Evaluation of Labeling
Those terms that are included in association with indication for drug.
Any labeling issues that are part of the post-marketing commitment.
26 Jul 2005

12. Post-marketing Commitments
Meeting additional regulatory obligations associated with drug approval may include:
Expediting abnormal liver function events
Expediting all pregnancies
Holding periodic meetings with medical experts
26 Jul 2005

13. Lessons from Regulatory Inspections
Document correspondence from meetings regarding adverse events.
Have a system of tracking all incoming events and source information from receipt at company to submission.
Track expedited reports. When reports are late, provide a reason for late submissions.
Have a procedure in place for determining when a case should be closed
Be prepared to produce safety training records for all company employees who are likely to hear of AEs (e.g. Supply Chain Mgmt)
26 Jul 2005

14. Lessons from Regulatory Inspections
Have written procedures for handling adverse events / product complaints.
Have contractual agreements with distributors and/or 3rd parties for collecting and reporting adverse events.
Be able to readily tabulate different types of event categories by time period, e.g. non-serious events, unlabeled, by quarter.
Be aware that the regulatory clock starts when an adverse event is confirmed. The generic ‘adverse event’ or ‘SAE’ does not meet the basic element of an AE.
26 Jul 2005

15. Summary
To accomplish the objectives of meeting the FDA’s Reporting Requirements is a collaborative effort for the entire company, involving not only all of the Drug Safety units, but also Regulatory Affairs, Clinical, Sales, and Marketing Departments.
26 Jul 2005