The FDA regulatory methods validation program for new and abbreviated new drug applications

This article describes the U.S. Food and Drug Administration (FDA) methods validation program for proposed regulatory methods submitted through the New and Abbreviated New Drug Application processes. The program is conducted by the Center for Drug Evaluation and Research (CDER) and the Office of Regulatory Affairs to ensure that scientifically well-founded regulatory methods are available to assess the quality of the CDER-approved products. The industry, FDA, and United States Pharmacopeia and National Formulary have the common objective of ensuring that drugs in the U.S. marketplace have consistent standards for drug substances and drug product regardless of the synthesis and manufacturing process. This may be accomplished by assuring that the analytical methods for new drug products are submitted for adoption as public standards soon after approval for marketing. The public standard provides a yard-stick for the named product which allows conscientious practitioners and consumers to determine if a product is as purported and thereby be able to detect spurious and sub-standard products in the marketplace. INTRODUCTION Validation of the analytical methods cited in a New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) is an important part of the U.S. Food and Drug Administration (FDA) drug review process. This validation effort, which is usually performed in two FDA laboratories, together with the validation performed by an applicant provides up to three independent assessments of an applicant’s methods to reliably determine the identity, strength, quality, purity, and potency of an approved new drug product. This article provides an overview of the FDA methods validation program conducted by the Center for Drug Evaluation and Research (CDER) in collaboration with the Office of Regulatory Affairs (ORA) for approved new and generic drugs. This article was developed as part of an effort to improve the efficiency of this program. 1 With the repeal of Section 507 of the Food Drug & Cosmetic Act, the antibiotic designations, which distinguished them from other drug products, have been eliminated. Methods validation approaches and issues for antibiotic drug products continue as those for all other new drugs currently approved under 505(b) and 505(j). 2 The United States Pharmacopeial Convention, 12601 Twinbrook Parkway, Rockville, MD 20852.