Challenges in application of new approaches to carcinogenicity testing for pharmaceuticals

Both evolutionary and revolutionary changes in testing and evaluation of the carcinogenic potential of pharmaceuticals have recently been embodied into guidances generated under the auspices of the International Conference on Harmonisation (ICH). These have formally been implemented and have changed the acceptable approaches available to industry and the evaluation necessary by regulatory authorities. The guidances increase flexibility, obligating industry and regulatory authorities to use more scientific, evidence-based decision making in their processes. The changes are anticipated to significantly improve the relevance of the assessment of carcinogenic risk for humans. The increased flexibility, the numerous decision points, the lack of comprehensive direction in the guidances, and the need for scientific justification of the testing approach, however, have led to confusion and occasional disagreement on appropriate test strategies for specific drugs. To address this problem in the United States, CDER engages in dialogue with industry to reach agreement on approach and dose selection prior to initiation of pivotal studies. Internationally, however, agreement on test approaches will only be achieved by broader communication between regulatory authorities that also involves industry. Published by Elsevier Science Ireland Ltd.