Bioanalytical Method Validation: What does the FDA expect?

FDA has published a draft guidance for industry with the title "Bioanalytical Method Validation" in September this year. In this guidance the content of the original guidance issued in 2001 has been revised to reflect advances in science and technology related to the area of bioanalytical methods.

This guidance explains the course of action for the validation of analytical procedures such as gas chromatography; high-pressure liquid chromatography; GC-MS; LC-MS; ligand binding assays, immunological assays and microbiological procedures. In doing so the specific features of these methods in the quantitative determination of drugs and metabolites in biological matrices, such as blood, serum, plasma, urine and different tissues are taken into account. There may be circumstances under which the method has to be modified depending on the specific conditions and therefore the guidance gives the indication that it is possible to deviate from the requirements described.

One of the most important updatings of this guidance is a chapter on incurred samples reanalysis, ISR. This analysis is carried out using the same method on different days in order to demonstrate its reliability. The procedure used for carrying out such a reanalysis is described in detail.

The other enlargements of the content of the guidance are summarised in the chapter "Additional Issues" and concern the distinction between the endogenous and the therapeutic compounds to be determined, the analysis of biomarkers, the particularities of the use of diagnostic kits (a new validation may be required with regard to a special analytical problem) as well as validation aspects for the latest bioanalytical technologies.

This guidance is directed to companies that submit investigational new drug applications (INDs), new drug applications (NDAs), generics applications (ANDAs) and biologic license applications (BLAs). This guidance also applies to analytical methods used for nonclinical pharmacological/toxicological studies. Its scope of application also includes studies on bioavailability, bioequivalence as well as pharmacokinetic studies on blood and urine related to the veterinary drug approval process.

As usual in the case of FDA draft-guidances you can comment the content within 90 days by means of the eRulemaking program.