Understanding and Implementing Efficient Analytical Methods Development and Validation

Analytical methods development and validation play important roles in the discovery, development, and manufacture of pharmaceuticals. The official test methods that result from these processes are used by quality control laboratories to ensure the identity, purity, potency, and performance of drug products.

By Jay Breaux, Ph.D., Kevin Jones, Pierre Boulas, Ph.D.

To ensure compliance with quality and safety standards, the United States, Europe, Japan, and other countries have published compendia, or pharmacopeias,that describe official test methods for many marketed drug products. For example, compendial analytical methods found in United States Pharmacopeia 25 (USP 25) are legally recognized analytical procedures under section 501 (b) of the Federal Food, Drug, and Cosmetic Act. For these compendial methods, USP provides regulatory guidance for method validation (1). In addition, validation of analytical methods is covered by the United States Code of Federal Regulations (CFR). Specific references are 21 CFR 211.165 (e) and 21 CFR 211.194 (a).

Method validation is defined as the process of proving (through scientific studies) that an analytical method is acceptable for its intended use. Recent guidelines for methods development and validation for new noncompendial test methods are provided by the FDA draft document, "Analytical Procedures and Methods Validation: Chemistry, Manufacturing, and Controls Documentation" (2). This recent document applies to the method development and validation process for products included in investigational new drug (IND), new drug application (NDA) and abbreviated new drug application (ANDA) submissions. Therefore, expectations from regulatory agencies for method development and validation are clear.

In recent years, a great deal of effort has been devoted to the harmonization of pharmaceutical regulatory requirements in the United States, Europe, and Japan. As part of this initiative, the International Conference on Harmonization (ICH) has issued guidelines for analytical method validation. The recent FDA methods validation draft guidance document as well as USP both refer to ICH guidelines (2). Analytical guidance documents recently published by the ICH are the following:
-- stability testing (Q1)
-- validation of analytical procedures (Q2)
-- impurities in drug substances and products (Q3)
-- specifications for new drug substances and products (Q6).
Additional regulatory guidance can be found on the FDA Web site www.fda.gov/cder/guidance and on the ICH Web site www.ich.org.

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