Analytical Methods Validation: Bioavailability, Bioequivalence, and Pharmacokinetic Studies

Abstract

0 This is a summary report of the conference on "Analytical Methods Validation: Bioavailability, Bioequivalence and Pharmacokinetic Studies." The conference was held from December 3 to 5,1990, in the Washington, D.C., area and was sponsored by the American Association of Pharmaceutical Scientists, the US. Food and Drug Administration, Federation International Pharmaceutique, Health Protection Branch (Canada), and the Association of Official Analytical Chemists. The report presents our assessment of the major agreements and issues discussed at the conference. The report is also intended to provide guiding principles for validation of analytical methods used in bioavailability, bioequivalence, and pharmacokinetics studies in humans and animals. The objectives of the conference were as follows: (1) to reach a consensus on what should be required in analytical methods validation and the procedures to establish validation; (2) to determine processes of application of the validation procedures in bioavailability, bioequivalence, and pharmacokinetics studies; and (3) to develop a report on analytical methods validation that may be referred to in developing future formal guidelines. Acceptable standards for documenting and validating analytical methods with regard to processes, parameters, or data treatments are discussed because of their importance in assessing pharmacokinetic, bioavailability, and bioequivalence studies. Other topics that were considered essential in the conduct of pharmacokinetic studies or in establishing bioequivalency criteria, including measurement of drug metabolites and stereoselective determinations, are also discussed. ___ -. ~. ~ _ _ Analytical methods that are used for the quantitative determination of drugs and their metabolites in biological samples play a significant role in evaluation and interpretation of bioavailability, bioequivalence, and pharmacokinetic data. It is essential to use well-characterized and fully validated analytical methods to yield reliable results that can be satisfactorily interpreted. Analytical methods and techniques are constantly being changed and improved; in many instances, these methods are at the cutting edge of the technology. It is also important to emphasize that each analytical technique has its own characteristics, which will vary from drug to drug. Moreover, the appropriateness of the technique may be influenced by the ultimate objective of the study. Specific validation criteria are needed for methods intended for analysis of each analyte (drug and/or metabolite). Although validation of each method will be independent of those of other methods, there may be situations in which comparison of the methods will be necessary (e.g., when more than one method has been used in a long-term study). When sample analysis is conducted at more than one site, it is necessary to validate the analytical methodb) at each site and provide appropriate validation information for different sites to establish interlaboratory reliability. Unless a method is used on a regular basis, providing confidence in its continued validity, it is essential to document that the method is still valid before analysis of samples in the study. Adequate validation for methods not used on a regular basis often consists of running a standard curve with new quality-control samples to show that the responses, relationship, and general characteristics of the method are similar to previous valida-