Vaccine Pre-clinical Toxicology Testing

About the authors

Polly Chang, Ph.D., Director of the Molecular Toxicology Program at the Biopharmaceutical Division, SRI International (http://www.sri.com/biopharm/), currently serves as Principal Investigator (PI) on the NIAID HIV vaccine contract NIAID-N01-AI-95375 and has supervised the successful preclinical safety testing of 6 candidate HIV vaccines under this program. Working closely with the project management and regulatory compliance teams in the preparation of the INDs, several of these vaccines have been approved by the FDA for Phase I clinical trials. Dr. Chang received her B.A. in mammalian physiology and her M.S. in Bioradiology/Biophysics, both from the University of California, Berkeley. She worked as a researcher at Lawrence Berkeley National Laboratory (LBNL), eventually attaining the position of Principal Research Associate before returning to the University of California at Berkeley to obtain her Ph.D. in Biophysics. The focus of her research was on the interactions of two clinical treatment modalities (hyperthermia and radiation) and the impact of de novo protein synthesis in in vitro cellular responses. Her global scientific experience during the 1990s includes working as a Visiting Scientist at the National Cancer Center, in Tokyo, Japan, and as a NIH Fogarty Fellow at the Cancer Biology Department, University of Tokyo Medical Center in Japan, examining the differential expression of a conserved family of homeotic genes in multi-step chemical carcinogenesis. In 1997 Dr. Chang joined SRI where, in addition to her vaccine work, she is currently the PI on a grant from NASA to apply transgenic mouse mutation models to study the mutagenic potential of charged particle radiation that mimics exposure that space travelers will receive. She is examining the expression of key genes that are involved in cell functions, linking perturbations in cellular systems after treatments with genotoxic agents to the misregulation of normal differentiation and pathophysiology. She also supervises a variety of molecular biology-related projects and serves as Study Director on several NCI studies to evaluate chemopreventive therapeutics. She is author or coauthor of over 30 publications.

CDR Rebecca Sheets, Ph.D., (USPHS) (http://www.niaid.nih.gov/vrc/key_sheets.htm) obtained her B.S. degree in Biology from the California Institute of Technology; M.S. degree in Cellular, Viral, and Molecular Biology from the University of Utah School of Medicine, and Ph.D. in Pathology from the University of Southern California School of Medicine. During 12 years of laboratory experience, she performed research in virology and viral pathology. Rebecca Sheets also worked in the pharmaceutical industry as a Clinical Research Associate, prior to obtaining her Ph.D. Her responsibilities were in the development, monitoring, and data auditing of clinical trials for cancer adjunct therapy with a biological cytokine. Dr. Sheets served for 9 years (1993-2002) as a Scientific Reviewer in the Viral Vaccines Branch of the Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review, CBER/FDA, reviewing Investigational New Drug Applications and Biologics License Applications. In 1994, to foster her commitment to public health, she became a Commissioned Officer in the U.S. Public Health Service (Scientist Category), in which she has been promoted to the rank of Commander (CDR). Since April 2002, Dr. Sheets is currently assigned as a Vaccine Scientific and Regulatory Specialist in the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. In this role, she serves the Division of AIDS and the Vaccine Research Center supporting the pre-clinical development of research concepts into HIV vaccine candidates suitable for human clinical trials.

Stuart Z. Shapiro, M.D., Ph.D., is currently a Medical Officer in the Preclinical Research & Development Branch, Vaccine & Prevention Research Program, Division of AIDS, National Institute of Allergy & Infectious Diseases where he provides scientific, clinical, technical, and budgetary planning, monitoring and management of grants, contracts, and cooperative agreements that support HIV/AIDS vaccine development with a focus on programs designed to facilitate the rapid transition of new vaccine designs through preclinical development into phase I human trials. Dr. Shapiro obtained his B.A. degree in Biochemistry from the University of California at Berkeley (1969), and his Ph.D. (Molecular Biology; 1976; thesis research on retrovirus protein synthesis) and M.D. (1977) degrees from Albert Einstein College of Medicine of Yeshiva University. He underwent medical internship training at Los Angeles County Harbor General Hospital after which he was a postdoctoral fellow and then a core Staff Scientist in tropical parasitic disease vaccine development for eight years at the International Laboratory for Research on Animal Diseases (ILRAD) in Nairobi, Kenya. He continued in parasitic disease vaccine research as an Assistant Professor of Veterinary Microbiology/Immunoparasitology and taught immunology and parasitology at the University of Illinois (Urbana-Champaign) from 1987 to 1993. In 1993 Dr. Shapiro joined the Division of Viral Products, Office of Vaccines, CBER, FDA as a laboratory-based reviewer and Senior Staff Fellow in retrovirology. In 1998, following 4 years at the FDA, Dr. Shapiro made a brief foray into industry as the sole proprietor of a regulatory affairs consultancy and vaccine design company. He came to his present position in DAIDS in September 1999 more fully aware of the difficulties vaccine developers face in getting their products into clinical trials. He is the author of a recent review (Shapiro, S.Z., Vaccine 2002; 20: 1261-1280) that attempts to explain to academic HIV/AIDS vaccine researchers, in plain English, what the FDA wants from them.

Sally J. Hargus, Ph.D., is currently a Toxicologist in the Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US FDA. She was recruited to FDA in July, 2001, following 5 years working in the pharmaceutical industry as a toxicologist. Dr. Hargus was a Fellow at the NIH from 1992-1996, in the laboratory of Lance Pohl, Pharm.D., Ph.D. She graduated from the University of Rochester School of Medicine and Dentistry in 1992, with a Ph.D. in Pharmacology.

Marion F. Gruber, Ph.D., is a scientific reviewer in the Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review (OVRR), Center for Biologics Evaluation and Research (CBER), FDA. Dr. Gruber received her B.Sc. in Microbiology from the University of Ulm, Germany in 1982, and her Ph.D. in Microbiology from the Christian Albrecht University of Kiel, Germany, 1986. She joined CBER in 1989 as a research scientist in the Office of Therapeutics Review and Research. Research interests have included the regulation of growth factor and cytokine expression of human B cells and monocytes. Dr. Gruber joined the Office of Vaccine Research and Review of CBER in 1995, where she is serving as scientific and regulatory reviewer for numerous Investigational New Drug applications and Biologic License applications. Dr. Gruber is chairing an inter-agency committee charged with developing policy and guidance for developmental toxicity study for preventive vaccines and serves on a number of national and international committees addressing preclinical safety assessment of these products. Dr. Gruber has presented CBER at a number of national and international meetings to discuss CBER policy pertaining to nonclinical safety evaluation of preventive vaccines and biological products.