Waivers for Carcinogenicity Studies? Not So Fast!

The recently published request for comments regarding the Proposed Change to Rodent Carcinogenicity Testing of Pharmaceuticals signals intent by regulatory agencies to alter what Sponsors consider in many cases to be unnecessary testing. However, it will be years before any actual waivers may be granted.

For now, FDA is proposing a pilot program in which Sponsors of pharmaceuticals currently subject to carcinogenicity testing under ICH S1A, prepare waiver requests but proceed with carcinogenicity testing as required. The purpose of this pilot program is to allow regulatory agencies participating in ICH to review: (1) the predictive potential of the waiver requests against actual carcinogenicity data, and (2) the concordance of decisions across regulatory agencies (U.S., Japan, E.U.) of the approvability of waiver requests. After approximately 50 of these “practice” waiver requests have been reviewed across ICH delegations, and evaluated for their ability to correctly predict carcinogenicity, FDA will decide whether to grant waivers in the future. It is estimated that the pilot program will take about 2 years to yield enough data to adequately evaluate the program. However, that time frame depends on the willingness of Sponsors volunteer to participate. Ultimately, the full implementation of a carcinogenicity testing waiver program for industry could take quite a while.

The need for beta-testing of the waiver program is a bit puzzling given that the agencies have used actual data from drug submissions in their databases to examine the predictive power of surrogate endpoints (e.g., mutagenicity, hormonal activity, and hyperproliferative lesions) and the feasibility of a waiver program. If consistency across regulators in the different regions was in question, it seems that existing data could be used to develop test cases for review by the different regulatory agencies. As for the ability of Sponsors to correctly predict potential carcinogenicity, this depends more on the state of the science than the ability of Sponsors to accurately frame an argument. If the science is there, the waivers should be able to be granted.