Bioanalytical Method Validation

Bioanalytical Method Validation is the backbone of drug discovery and development. Studies requiring validated methods include human clinical and pre-clinical studies, bioavailability, bioequivalence, and pharmacokinetic studies, as well as non-human pharmacokinetic/toxicology and pre-clinical studies falling under the scope of Good Laboratory Practices (GLPs), as outlined in 21 CFR 58. A validated method ensures that study sample analysis of biological matrices for quantitative determination of drugs and/or metabolites will be reliable, rugged, and repeatable. The FDA Guidance for Industry, Bioanalytical Method Validation, lists a number of elements contributing to the establishment and verification of an analytical method. In addition to prescribing specific laboratory studies, there are a number of documentation and reporting requirements for demonstrating the validity of a method for bioanalytical sample analysis. Method validation practices and documentation are a central focus of FDA audits; many Form 483 findings relate directly to the integrity of the validation process.

Quality by Design

Bioanalytical method validation relies on more than accuracy, precision, and repeatability. Regulatory focus is shifting to a lifecycle approach for method validation, which reflects how the method will integrate with its intended operating environment and includes provisions for continued monitoring and improvement. The method becomes a functional unit of your whole quality system. Qualified facilities and equipment, validated systems, and properly-trained personnel are the foundation of high-quality method performance. By linking the method validation project to your Validation Master Plan, all elements of your quality program can be cited in direct support of your method validation activities.

Additional Resources

Additional information is available on specific types of validation: