On May 21, 2018, FDA issued final guidance on Bioanalytical Method Validation. The guidance incorporates public comments to the revised draft published in 2013, which followed an initial release of guidance in 2001, and reflects advances in science and technology. The guidance describes the elements of bioanalytical method development and validation that are needed to ensure the quality of an assay and the reliability of the data it generates.
The guidance is meant to help when validating bioanalytical methods used in human clinical pharmacology, bioavailability, and bioequivalence studies and applies to bioanalytical procedures such as chromatographic assays and ligand binding assays that quantitatively determine the levels of drugs, their metabolites, therapeutic proteins, and biomarkers in biological matrices such as blood, serum, plasma, urine, and tissue such as skin. The guidance may also inform the development of bioanalytical methods used for certain nonclinical studies.
Before the development of a bioanalytical method, FDA recommends the sponsor understand the analyte of interest (e.g. the physiochemical properties, metabolism, binding) and consider aspects of any prior analytical methods that may be applicable. The sponsor should then optimize the procedures and conditions involved with extracting and detecting analyte with an emphasis on certain bioanalytical parameters, such as references standards, critical reagents, calibration curve, quality control samples, selectivity and specificity, sensitivity, accuracy, precision, recovery, and stability.
FDA also identifies recommended steps for bioanalytical method validation. Specifically, the sponsor should:
- conduct a full validation of any new bioanalytical method for the analysis of a new drug entity, its metabolite(s), or biomarkers;
- conduct a full validation for any revisions to an existing validated method that adds a metabolite or an additional analyte;
- establish a detailed, written description for the bioanalytical method before initiating validation;
- document and report all experiments used to make claims or draw conclusions about the validity of the method; and
- validate the measurement of each analyte in the biological matrix.
The elements and acceptance criteria of method development and validation are summarized in Table 1 of the guidance. Recommended documentation for method validation and bioanalytical reports are specifically described in Table 2.