Abstract A34: Cancer prevention in practice at FDA

Most major categories of products reviewed at the U.S. Food and Drug Administration (FDA) undergo assessment for cancer hazard, which generally is accomplished by using qualitative findings from genotoxicity tests. In some instances, two-year rodent bioassays are used for quantitative risk assessment. In the attempt to minimize the use of animals, more recently alternative approaches have included the assessment of data from chemical characterizations, QSAR, and toxicology risk assessments. Although the focus is primarily on hazard identification, or classification of agents as genotoxic or nongenotoxic, the scope of consideration is broader, including identification of potential nongenotoxic carcinogens and consideration of negative factors for carcinogenesis, such as the absence of hormonal action, rodent neoplasia, and certain histopathologic risk factors. For many (but not all) product categories, review generally includes a risk/benefit assessment. A diversity of laws, regulations, standards, and products affects the approach to cancer risk assessment in different FDA centers. Other than tobacco, little is known about the actual human risk of many products or combinations of foods, drugs, medical devices, and other exposures, over days, years, or a lifetime, relative to cancer risk. Thus, it is difficult to find yardsticks against which to consider new products. In thinking about risks to human health and the potential for tumor development, it is useful to consider the factors generally understood to be important from animal and human studies in carcinogenesis, especially from human experience with tobacco: dose, frequency, and duration of exposure; multiple exposures to agents acting via different mechanisms; inflammatory or proliferative responses; susceptible systems (based on genetics, age, or development); and time available for tumor development. High-dose single-agent testing in animals has been validly criticized as a poor model for human cancer risk, particularly given the expense, time, and large numbers of animals required. Replacement models suitable for FDA premarket product safety review are needed, particularly representing the real world of multiple exposures and individual human susceptibilities. Citation Format: Rosalie K. Elespuru. Cancer prevention in practice at FDA [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A34.