Regulatory Concerns at Various Phases of Drug Development

Abstract

This review of US Food and Drug Administration regulatory concerns at each phase of drug development, based on precedents in the area of prevention and treatment of atherosclerosis, is undertaken in anticipation of future pharmaceutical developments in this field. These include new drugs based on modifications of currently available agents, enabling increased potency in lipid lowering; drugs acting through novel mechanisms to alter plasma lipoprotein levels and structure; and therapies whose presumed salutary actions in decreasing atherosclerotic disease risk are via nonlipid effects (perhaps therefore to be used in combination with lipid-altering agents or in patients ineligible for or intolerant of these agents). Only clinical regulatory aspects will be addressed. Those interested in nonclinical technical requirements should consult directly with the FDA. General guidelines on the timing and duration of nonclinical safety studies needed to support human clinical trials at each phase of drug development are also under development through the International Conference on Harmonization (ICH). 1. Timing of nonclinical studies for the conduct of human clinical trials. International Conference on Harmonization M3, May 1997. Google Scholar Specific ICH guidelines in the areas of carcinogenicity, 2. Guideline on the need for carcinogenicity studies of pharmaceuticals. International Conference on Harmonization S1A, November 1995. Google Scholar reproductive toxicity, 3. Detection of toxicity to reproduction for medicinal products. International Conference on Harmonization S5A, June 1993. Google Scholar and genotoxicity are currently available. 4. Genotoxicity: standard battery testing. International Conference on Harmonization S2B, April 1997. Google Scholar