Docket Management
Docket: 00N-1484 - Safety Reporting Requirements for Human Drug & Biological Products
Comment Number: EC -3

Accepted - Volume 1

Comment Record
Commentor Dr. James Nickas Date/Time 2003-03-15 11:15:51
Organization Genentech, Inc.
Category Health Professional

Comments for FDA General
1. General Comments COMMENTS ON PROPOSED SADR DEFINITION The proposed SADR definition intimates that any observed adverse event (presumably limited to treatment emergent adverse events) for which a possible causal relationship cannot be ruled out is potentially drug related. The proposed SADR definition could be interpreted to imply that all reported SADRs should be included in applicable reference safety informaton documents (e.g., package inserts, investigator brochure, informed consent form, etc) if a causal relationship cannot be ruled out. Possible causal relationships can almost never be excluded with 100% certainty for events that have multiple potential causes (e.g., disease-related events). Implementation of the proposed SADR concept without further clarification could encourage the inclusion of long laundry lists of irrelevant adverse events in applicable reference documents , with the assumption that this makes them expected for regulatory reporting purposes. This would significantly dilute the quality and usefulness of safety information in product labeling. Previously published FDA and CIOMS V safety labeling guidance encourages inclusion of adverse events in product labeling only when a causal or contributory relationship is suspected, reasonably established or inferred based on facts (evidence) or plausible arguments that point to such a relationship. The Agency is encouraged to clarify in regulations and/or guidance documents 1) the bar for spontaneous and clinical trial reporting of observed adverse events to the Agency, manufacturers and sponsors (e.g., serious +/- nonserisous treatment emergent adverse events regardless of causal attribution), 2) general casuality assessment guidance that can be applied to individual case safety reports for expedited reporting purposes to the Agency, and 3) clearer guidance on what is considered expected or unexpected for regulatory reporting purposes. With respect to the latter, only events that are listed in applicable reference safety information documents and cleary positioned as true adverse drug reactions (e.g., possibly related based on data) should be considered expected for regulatory reporting purposes. Codifying this concept in safety reporting regulations will normalize and improve the meaningfulness of expedited safety reports to the Agency.

EC -3