Genotoxicity and Carcinogenicity Testing of Pharmaceuticals

Introduction.- History and Current Regulatory Requirements.- Genotoxicity Testing of API and Impurities.- New Emerging Genotoxicity Tests.- Carcinogenicity Testing of Small Molecules.- Alternatives to the 2-Year Rodent Studies.- Addressing Positive Findings in Carcinogenicity Studies.- Investigating Tumor Signals in Clinical Trials.- Tumor Promoters.- Carcinogenicity Testing of Biologics.- In Silico Predictive Tests.

Michael J.Graziano, Ph.D., has more than 27 years of experience as atoxicologist in the pharmaceutical industry. He is currently Vice President ofDrug Safety Evaluation at Bristol-Myers Squibb, where he is responsible for thenonclinical safety testing for all drugs within the BMS portfolio. Within thepast 6 years, he has provided nonclinical support for 8 new drug approvals.Prior to joining BMS in 2003, he was Director of Anticancer and AntibacterialToxicology Programs at Pfizer Pharmaceutical Research, in Ann Arbor, MI, and withthe Parke-Davis Pharmaceutical Research Division/Warner-Lambert Company. He isthe author or co-author of more than 90 scientific publications and abstracts,many dealing with the nonclinical safety of new therapeutic agents. Dr.Graziano is a member of the IQ DruSafe Leadership Group, the PhRMA Clinical andPreclinical Development Committee, the EFPIA PreclinicalSafety DevelopmentCommittee, and HESI. He is also the PhRMA Deputy Topic Leader for the currentICH S1 Expert Working Group. Dr. Graziano received a B.S. in animal sciencefrom Rutgers University, a M.S. in veterinary toxicology from Louisiana StateUniversity, and a Ph.D. in toxicology from the University of Kentucky, and wasa Post-Graduate Research Toxicologist at the University of California,Berkeley. He is also a Diplomate of the American Board of Toxicology.

DavidJacobson-Kram received his Ph.D. in embryology from the University ofConnecticut; he then went on to serve as a staff fellow at the NationalInstitute on Aging. After leaving the National Institutes of Health, Dr.Jacobson-Kram joined the faculty of the George Washington University School ofMedicine and then later, Johns Hopkins University Oncology Center. During thissame period he served, on a part-time basis, asa geneticist in the Office ofToxic Substances at the Environmental Protection Agency and as Acting BranchChief in the EPA's Office of Research and Development. Dr. Jacobson-Kram servedas the Vice