Adverse Experience Information Management

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Transcript Adverse Experience Information Management

The Information Professional’s
Role in Product Safety
Jack Leitmeyer
Director, Adverse Experience Information
Worldwide Product Safety
Merck & Co., Inc.
Importance of Safety Surveillance
Regulatory Requirements
Role of the Adverse Experience (AE)
Information Professional
Future Opportunities
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
Benefit–risk safety profile changes over time
Adverse Experience Reporting to FDA
Pre-Approval - To IND
7 calendar day reports (telephone or facsimile)
15 calendar day reports to IND
Unexpected fatal or life-threatening experience associated with the use
of the drug
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
Reports in the scientific literature including unpublished manuscripts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)
Adverse Experience Reporting to FDA
Post-Approval - To IND
 15 calendar day reports to IND
 From IND Studies (Serious, Drug-Related and
 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
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.”
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.”
Business Impact
Monetary Loss
Penalties per Violation (Section 303
FD&C Act)
Fines and/or Jail
AE Information Management
Call Center
Reports / Queries
Data Mining
Clinical (MedDRA) /
Drug Dictionaries
Submission database
Investigator Portal
Clinical Risk Mgt.
Clinical Trial data
Regulatory Agencies
Imaging System
Business Partners
Product Labeling
Clinical Literature
Role of the AE Information Professional
o Helpful Experience:
• Clinical terminology
• Worldwide safety regulations
• Technology
• Six Sigma Methodology
Role of the AE Information Professional
o Safety Database Oversight
o Reference Data Management
o Document Management
o Dictionary Management
o Queries / Reports
o Quality Control
Role of the AE Information Professional
o 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
Role of the AE Information Professional
o Safety Database Oversight – ICH E2B
• ICH = International Conference on Harmonization
• ICH E2B - Standardized essential data elements for
electronic transmission of individual case safety reports:
1. Patient characteristics
2. Reactions/Events
3. Results of tests and procedures relevant to investigation of
4. Drug(s) Information (e.g., status, generic, tradename,
marketing authorization number)
5. Narrative Case Summary (e.g., case summary, sender’s
opinion of overall diagnosis/syndrome or reclassification of
reporter terms)
Role of the AE Information Professional
o Reference Data Management
• Clinical Trial protocol and site numbers
• Allocation schedules
• Drug formulations
• Routes of administration
• Country Lists
• NDA / IND numbers
• Journal Titles
• etc.
Role of the AE Information Professional
o Document Management
• Record Retention Policy
• “Official” Files – paper / electronic records
• Patient Privacy
• Access to shared procedures
• Access to training material
Role of the AE Information Professional
o 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).
Role of the AE Information Professional
o 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
Role of the AE Information Professional
o Quality Control
• Data Entry sampling
• Coding Review
• Electronic submission tracking
• Compliance monitoring
Future Opportunities
o Evolving Regulations
o Global Harmonization
o Electronic Transfer of Data
o Links to External Databases
o Data Mining