Docket Management
Docket: 00N-1484 - Safety Reporting Requirements for Human Drug & Biological Products
Comment Number: EC -1

Accepted - Volume 1

Comment Record
Commentor Dr. James Nickas Date/Time 2003-03-14 19:40:35
Organization Genentech, Inc.
Category Health Professional

Comments for FDA General
1. General Comments COMMENTS ON PROPOSED SADR DEFINITION The Agency is proposing to incorporate the terms suspected adverse drug reaction (SADR) and serious adverse reaction (SAR) into applicable pre- and post-marketing safety reporting regulations to replace the terms associated with the use of the drug, adverse drug experience and adverse experience. The proposed definition for a SADR is said to include adverse events for which a causal relationship cannot be ruled out. The proposed SADR definition intimates that classifying a case as possibly related, probably related, remotely related, or unlikely related to a drug or biological product (as is commonly done by investigators participating in clinical trials) would signify that a causal relationship between the product and the reported adverse event could not be ruled out and, thus, the adverse event would be considered a SADR. Although the Agency has indicated that the proposed SADR definition is consistent with the ICH definition of an adverse drug reaction (ADR), the i.e. notation in the ICH ADR definition that suggests an adverse event should be considered an ADR when a possible causal relationship cannot be ruled out has been considered problematic by many Pharmacovigilance specialists. Since it is rarely possible to rule out a causal or contributory relationship with absolute certainty until cumulative unblinded study data are analyzed, implementation of the proposed SADR definition in clinical trials could significantly increase the number of expedited safety report submissions to the Agency with questionable gain. Submitted for consideration is the following alternative definition for SADR, which may be more consistent with industry's interpretation of an ADR: A noxious and unintended response to any dose of a drug or biological product for which a causal or contributory relationship is suspected, reasonably established or inferred based on facts (evidence) or plausible arguments to suggest a causal or contributory relationship.

EC -1