ICH V2 An FDA Update Susan Lu Office of Drug Safety Center for Drug Evaluation and Research FDA January 21, 2003

V2 Draft Version 3.0 POST-APPROVAL SAFETY MANAGEMENT: DEFINITIONS AND STANDARDS FOR EXPEDITED REPORTING AND GOOD CASE MANAGEMENT PRACTICES

Background Topic adopted February 2002 (Brussels) Meetings of Expert Working Group to date: June 2002 London Sept 2002 Washington D.C. FDA representatives –CDER - Susan Lu, Min Chen (back-up) –CBER - Tim Cote

Principles Expansion of ICH E2A to post-approval phase  Consistency with E2A document in content Inclusion of relevant CIOMS-V recommendations where applicable

Current Status Step 1- discussion and consensus building among EU, Japan, and U.S. Moving towards finalization of draft for Step 2

Overview of FDA Goals and Comments Consistency with U.S. regulations -definitions Sound Good Reporting Practices Editorial Clarification and further discussion

Overview of V2 draft document I. Introduction II. Definitions and Terminology Associated with Post-approval Drug Safety Experience III. Standards for Expedited Reporting IV. Good Case Management Practice

I. Introduction “ To establish an internationally standardized procedure to improve the quality of post- approval safety information, to harmonize the way to gather information, and if necessary, to take action”

II. Definitions and terminology associated with post-approval drug safety experience Basic terms - Adverse event (AE), Adverse Drug Reaction (ADR) Serious AE/ADR Expectedness and Listedness of ADR Other definitions Sources of Individual Case Reports

Definition of Adverse Event An adverse event is an untoward medical occurrence in a patient administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment

Definition of adverse reaction A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease or for modification of physiological function. (WHO technical report 498, 1972) All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase” responses to medicinal products” means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e. the relationship cannot be ruled out. (ICH E2A)

Definition of Expectedness of an Adverse Drug Reaction An “unexpected” adverse reaction is one, the nature, severity, specificity or mechanism is not consistent with the term or description in the local product labeling. “Class ADRs” should not automatically be considered to be expected for the subject drug…expected only if the product is itself implicated.

Sources of Individual Case reports Unsolicited sources- spontaneous reports, consumer reports, literature, internet, other non medical sources (lay press) Solicited sources- study reports, organized data collection systems Licensor-licensee interaction Regulatory authority sources

III. Standards for Expedited Reporting A. What Should be Reported? B. Reporting Time Frames

III. A. What Should be Reported? As a rule, cases of adverse drug reactions that are both serious and unexpected are subject to expedited reporting.

III. B. Reporting Time Frames Time clock start point Minimum Criteria for Reporting

IV.Good Case Management Practice Assessing Patient and Reporter Identifiability Role of Narratives Single Case evaluation Follow up information How to report