Bioanalytical Method Development and Validation: from the USFDA 2001 to the USFDA 2018 Guidance for Industry

Abstract

Recently, the USFDA issued the new 2018 guidance document for industry on bioanalytical validation. Due to this occasion, it would be worthy to look back in time as well into the (near) future on potential practical impacts the 2018 guidance document might have on bioanalytical method validation and laboratory operations. Bioanalytical method development and validation is the most important part in regulated bioanalysis. Validated bioanalytical methods are used for the quantitative measurement of drugs and their metabolites, endogenous compounds, and biomarkers in biological fluids. Drug concentrations are indispensable for the evaluation and interpretation of pharmacokinetic (PK), toxicokinetic (TK), and bioequivalence (BE) study data. The bioanalytical methods are not only applied for quantification of small molecules (molecular weight ≤ 900 Da) but also for larger molecules such as proteins, antibodies, and peptides. Bioanalysis can be quite challenging due to the complexity of the biological sample matrix. In addition to the sample complexity, data quality obtained from analyzed samples is directly related to the bioanalytical method’s performance. Without any doubt, it is of utmost importance that bioanalytical methods used in bioanalysis have to provide reliable data. According to the USFDA is the purpose of bioanalytical method validation: 1) to validate operation conditions, limitations, and 2) to determine the method suitability for its intended purpose and 3) to ensure that the bioanalytical method is optimized for sample analysis. For a long time, method validation procedures and strategies used in bioanalysis, as well as acceptance criteria needed for validation procedures, were a matter of personal prejudice. Many years there existed a lack of guidance uniformity on bioanalytical method development and validation within the bioanalytical community. This suddenly changed when industrial committees and regulatory agencies initiated the development and introduction of guidance documents on bioanalytical method validation for industry [1]. The first USFDA guidance document for industry on bioanalytical method validation was issued as a draft guidance in January 1999. Two years later this draft guidance document was finalized after incorporation of public comments, and the guidance was released as an official guidance document in May 2001. The guidance docuMLM Medical Labs GmbH, Dohrweg 63, 41066 Mönchengladbach, Germany.