Four Decades of History & Evolution of Clinical Pharmacology at US Food and Drug Administration (FDA)-Part II: Dose Individualization and Approvability Evidence.

The Office of Clinical Pharmacology (OCP) is a part of the Center for Drug Evaluation and Research (CDER) at the FDA. OCP is likely the largest group of scientists with expertise in the evaluation of all aspects of clinical pharmacology in new drug development, approval, and life cycle management. This article details the growth of this office over the last 40 years from one small Division of Biopharmaceutics (DB) in 1986, with staff of about 30 members carrying a large backlog of applications, to the current OCP of approximately 270 scientists with needed resources to carry out thousands of reviews and industry meetings in a timely manner. The growth of OCP is detailed with milestone developments in the areas of biopharmaceutics (BP) and CP science, which became a part of the review focus of new drug and biological applications over the last 40 years. Part I covered the organizational evolution of the OCP and the first segment of its scientific growth, i.e., bioanalysis, specific topics in the areas of bioavailability (BA) and bioequivalence (BE), biosimilars, and new drug applications (NDAs) on the basis of Sect. 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDC Act). Part II covers the areas of metabolism and drug‒drug interactions (DDI), including DDI-induced fatal terfenadine cardiotoxicity, special populations, pediatric efficacy extrapolation, pharmacogenomics, quantitative clinical pharmacology (QCP), and conclusions.