How To Perform Rapid Bioanalytical Assay Development And High-Quality Fit For Purpose Method Validation?
Currently, much of the early drug development studies are conducted in small or mid-size bioanalytical testing services. Several large biopharma companies have started working with them for services such as early developmental studies, bioanalysis of samples, and method development services. Outsourcing drug development work means the focus shifts on analytical method transfer in pharma. Test method transfer helps to ensure that the results generated are carried out using methods meeting all the expectations of the sponsor and regulatory agencies.
Regulatory guidelines for late-stage studies require full analytical method development and validation for GLP or human clinical studies. Although bioanalytical assays should be adequately developed, method validation generally is done through fit-for-purpose approaches. Let us understand how to perform method development and fit for purpose method validation.
Bioanalytical method development
Bioanalytical method development defines the study design, operating parameters, study limitations, method suitability and ensures method optimization for subsequent assay validation. Before developing any bioanalytical method, sponsors should first consider researching aspects of any prior methods that may deem suitable. Moreover, sponsors should determine fundamental characteristics of the analyte, which include in vitro-in vivo characteristics, protein binding, and physicochemical properties.
Method development optimizes assay protocols and experimental conditions that are concerned with analyte extraction and detection. To ensure method suitability for validation, method development optimizes several parameters, including critical reagents, reference standards, QC samples, calibration curve, sensitivity, selectivity and specificity, precision, accuracy, recovery, and analyte stability.
Extensive notation or record-keeping is not needed for bioanalytical method development. However, if sponsors change any aspect of the assay method, they should record those changes along with any related issues that may have arisen during assay modification.
Fit for purpose method validation
Fit for purpose assay validation means the validation level should suit the intended use of the assay. Compared to full assay validation, fit-for-purpose validation is much easier to perform and matches all the client’s requirements. The primary goal of fit for purpose assay validation is to conduct studies while fulfilling GLP regulations. Bioanalytical testing services employ fit-for-purpose validation for evaluating the accuracy, precision, sensitivity, selectivity, and stability throughout the drug development process.
Does the assay quantify the analyte of interest? Is there any associated variability? What is the measurement range? Does the logistics affect assay reliability? These are some of the vital questions to consider before initiating fit for purpose assay validation. As mentioned earlier, this approach focuses on the intended use of an assay. So critical studies such as the ones involved in BLA, NDA, and ANDA submissions that are critical for regulatory decisions will require a fully validated bioanalytical assay. Exploratory assays such as assays for candidate selection that do not support regulatory criteria will not require a full stringent method validation. Fit for purpose assay validation is considered for biomarkers, and drugs and their metabolites.
The road ahead
A thoroughly developed and validated bioanalytical assay is a prerequisite for a successful drug development process. Hence, method development services should have an open discussion with sponsors to decide the extent to which an assay validation is needed.