The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Abstract for TestSmart--Pharmaceuticals: An Efficient and Humane Approach to Predictors of Potential Toxic Effects of Drugs

Requirements For Safety Evaluation Of Pharmaceuticals--What Do We Need To Know? How Do We Obtain The Information Today?

James T. MacGregor
National Center for Toxicological Research, US Food and Drug Administration

The general requirement for approval of a new human pharmaceutical is demonstration of the safety and efficacy of the proposed use. Preclinical safety studies currently rely heavily on animal studies. These usually consist of studies of various durations, depending on the length of clinical exposure and the endpoint being evaluated. Traditional biomarkers of general organ and tissue damage include morphological alterations (histopathological evaluation), serum markers of cell integrity (loss of cytoplasmic AST,ALT, ALP, etc.), indicators of homeostasis (BUN, creatinine, electrolytes), and the presence of host-defense cells in tissues (macrophages, lymphocytes, etc.). Special testing is conducted to evaluate developmental and reproductive toxicity, carcinogenicity, mutagenicity, and neurotoxicity. Advances in our understanding of the molecular basis of cellular damage and response have created new opportunities for improved molecular biomarkers of cell and tissue damage and have led to new laboratory models based on our mechanistic understanding of molecular pathology. Of particular importance is the possibility of employing "bridging biomarkers" that permit assessment of subpathological damage in both humans and laboratory models. These new biomarkers offer the potential to improve both the efficiency of laboratory animal testing and the reliability of extrapolations of laboratory findings to the human.