1. The Information Professional’s Role in Product Safety
Jack Leitmeyer
Director, Adverse Experience Information Management
Worldwide Product Safety
Merck & Co., Inc.

2. Agenda Importance of Safety Surveillance Regulatory Requirements
Role of the Adverse Experience (AE) Information Professional
Future Opportunities

3. Importance of Safety Surveillance
Compliance with Government Laws and Regulations
Timely and Accurate Monitoring of the Safety Profile of Products
Limitation of human data in clinical trials
Small study populations
Restricted enrollment
Limited long term safety data
Widespread use of the product in the post-marketing environment
Benefit–risk safety profile changes over time

4. Adverse Experience Reporting to FDA
Pre-Approval - To IND
7 calendar day reports (telephone or facsimile)
Unexpected fatal or life-threatening experience associated with the use of the drug
15 calendar day reports to IND
From All Studies Worldwide (Serious, Drug-Related and Unexpected)
Findings from tests in laboratory animals suggesting a significant risk to humans (mutagenicity, teratogenicity, carcinogenicity)
Spontaneous Reports from Marketing Outside the U.S. (Serious and Unexpected)
Reports in the scientific literature including unpublished manuscripts (Serious and Unexpected)
Reports from foreign regulatory authorities (Serious and Unexpected)
Annual IND reports
From Studies Worldwide (Serious)

5. Adverse Experience Reporting to FDA
Post-Approval - To IND
15 calendar day reports to IND
From IND Studies (Serious, Drug-Related and Unexpected)
Annual IND Report
From IND Studies (Serious)
Post-Approval - To NDA
15 calendar day reports to NDA
From All Studies Worldwide (Serious, Drug-Related
and Unexpected)
Spontaneous Reports Worldwide (Serious and Unexpected)
Periodic Reports to NDA

6. Failure to Report Pre-Approval - Termination of IND 21 CFR 312.44
Phase 1, 2 or 3
(b)(1)(vii) “The sponsor fails promptly to investigate and inform the Food and Drug Administration and all investigators of serious and unexpected adverse experiences in accordance with part 312 section 32 or fails to make any other report required under this part.”

7. Failure to Report Post-Approval- Withdrawal of NDA 21 CFR 314.80 (K)
“If an applicant fails to establish and maintain records and make reports required under this section FDA may withdraw approval of the application and, thus, prohibit continued marketing of the drug product that is the subject of the application.”

8. Business Impact Product People Monetary Loss
Penalties per Violation (Section 303 FD&C Act)
Fines and/or Jail

9. AE Information Management
Call Center
Reports / Queries
Data Mining Applications
Regulatory Submission database
Clinical (MedDRA) / Drug Dictionaries
Investigator Portal
AE database
Clinical Risk Mgt.
Clinical Trial data
Regulatory Agencies
Imaging System
Business Partners
Product Labeling
Clinical Literature

10. Role of the AE Information Professional
Helpful Experience:
Clinical terminology
Worldwide safety regulations
Technology
Six Sigma Methodology

11. Role of the AE Information Professional
Safety Database Oversight
Reference Data Management
Document Management
Dictionary Management
Queries / Reports
Quality Control

12. Role of the AE Information Professional
Safety Database Oversight
Information moving electronically between business partners and regulatory agencies
Managing large datasets (over a million episodes)
Mapping data fields across systems
What data are required by safety department and regulatory agencies
Algorithms for information flow
Routing algorithms for data entry
Routing to countries / agencies / business partners
Rules for reportability

13. Role of the AE Information Professional
Safety Database Oversight – ICH E2B
ICH = International Conference on Harmonization
ICH E2B - Standardized essential data elements for electronic transmission of individual case safety reports:
Patient characteristics
Reactions/Events
Results of tests and procedures relevant to investigation of patient
Drug(s) Information (e.g., status, generic, tradename, marketing authorization number)
Narrative Case Summary (e.g., case summary, sender’s opinion of overall diagnosis/syndrome or reclassification of reporter terms)

14. Role of the AE Information Professional
Reference Data Management
Clinical Trial protocol and site numbers
Allocation schedules
Drug formulations
Routes of administration
Country Lists
NDA / IND numbers
Journal Titles
etc.

15. Role of the AE Information Professional
Document Management
Record Retention Policy
“Official” Files – paper / electronic records
Patient Privacy
Access to shared procedures
Access to training material

16. Role of the AE Information Professional
Dictionary Management
Medical Dictionary for Drug Regulatory Activities (MedDRA*)
Company procedures related to global standard dictionary
Feedback to MedDRA Maintenance and Support Services Organization (MSSO)
Participation in Industry User Group
Drug Dictionary *
MedDRA® is a registered trademark of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA).

17. Role of the AE Information Professional
Queries / Reports
Provide output for monitoring product safety and responding to safety questions.
Ensure proper validation and testing (21 CFR Part 11)
Information Specialist can provide input on:
What data fields are available ?
Search all versions, latest versions, or latest completed versions?
Have the data values changed over time as regulations, procedures, and databases have changed ?
What MedDRA terms / term groupings should be used to query the database ?
What is the best format for the output?
What is correct skill set required for writing and executing database queries?

18. Role of the AE Information Professional
Quality Control
Data Entry sampling
Coding Review
Electronic submission tracking
Compliance monitoring

19. Future Opportunities Evolving Regulations Global Harmonization
Electronic Transfer of Data
Links to External Databases
Data Mining