Over the past 25 years the criteria required for bioanalytical methods has evolved significantly. The harmonization of bioanalytical methods requirements started in 1990 during the AAPS and FDA Crystal City Meetings. In 2000 the Crystal City II Meeting laid the foundations of the 2001 FDA Guidance on Bioanalytical Method Validation. In 2011 EMA launched his own guideline on bioanalytical method validation which provides recommendations for the validation of bioanalytical methods applied to measure drug concentrations in biological matrices obtained in animal toxicokinetic studies and all phases of clinical trials. These guidelines harmonized the bioanalytical method validation involved in preclinical, clinical and bioequivalence studies. However, the requirements to fulfil the guideline are costly and time consuming and do not match with the industry needs when the bioanalytical assays are designed to take low relevance decisions in earlier phases of drug development and when used in special matrixes.
Since 2006, the concept fit-to-purpose approach has became part of bioanalytical discussion when a tiered approach to bioanalytical method validation was proposed in Crystal City III. The tiered approach concept involves different levels of scientific validation as an alternative to apply full established regulatory validation principles. This more flexible approach allows to split between four decreasing levels of method performance and evaluation depending on the bioanalytical data final purpose: 1) Validation, intended for regulatory studies, 2) Qualification, 3) Research, and 4) Screening.
More recently, industry representatives (within the European Bioanalytical Forum) proposed rebranding this tiered approach into scientific validation aimed at emphasizing the quality of the data generated by this alternative validation workflows, while adhering to the goal of optimizing science and resources. They defined a practical application of this concept into five key areas of bioanalytical support: 1) Quantification of metabolites in early development (as recommended in Crystal City III), 2) Urine analysis in all stages of development, 3) Tissue (homogenate) analysis also in all stages of development, 4) Clinical studies in early stages of drug development, and 5) Non-pivotal early preclinical GLP studies.
The qualification plan for fit-to-purpose scientific validation should be properly justified to meet the study objectives with an adequate level of data reliability and quality.