Regulatory Review

Within the Center for Drug Evaluation and Research (CDER) of the FDA, the regulatory review of clinical pharmacology and biopharmaceutics studies is the responsibility of the Office of Clinical Pharmacology and Biopharmaceutics (OCPB). The mission of OCPB has patient care and therapeutics as center stage, and this is reflected by the scientific goals of clinical pharmacology and biopharmaceutics, that is, to critically study, thoroughly understand, and successfully identify (1) the right dose, in (2) the right dosage form, for (3) the right patient. The final step is to responsibly translate this knowledge to the product label with appropriate information about the use of the drug/drug product in the clinical pharmacology, precautions, warnings, contraindications, and/or dosage and administration sections of the package insert. This is indeed a critical step in the review process, since labeling a drug for use in the manner that is intended for patients to use it (or not use it) is one of the most important ways of risk management for ADRs.

OCPB's review process is based on a paradigm known as the Question-Based Review, or QBR [10]. It recognizes that it would be unreasonable to expect that everything will be known about the clinical pharmacology (CP) and biopharmaceutics (BP) of a drug/drug product at the time of NDA submission. Accordingly, the QBR emphasizes the importance of the reviewer's responsibility to ask the right questions related to the efficacy and safety of new medicines based on the clinical pharmacology and biopharmaceutics database provided by the sponsor in a NDA, and also to identify what is important but not known about the drug. The latter may be the basis for postmarketing studies (phase IV commitments). There are many critical principles in applying the QBR but two stick out the most when reviewing CP and BP studies: (1) analyzing study results and integrating knowledge thoughtfully across studies, and not just reviewing studies in isolation from one another, or necessarily in the chronological order in which they were conducted, and (2) interpreting results of CP and BP studies in the overall context of what is also known from the nonclinical chemistry, pharmacology and toxicology data, and the clinical efficacy and safety information, and not just to focus on providing a narrow-focused CP/ BP report to medical officers. To meet these responsibilities, reviewers are strongly encouraged to act credibly and to communicate extensively with other professionals during the review process.

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