Drug development companies consistently apply for IND, NDA, and ANDA applications to the US FDA. For a successful drug application, sponsors have to conduct clinical and nonclinical studies, BA/BE evaluations, and pharmacokinetic/pharmacodynamic assessments. The successful conduct of these studies needs a thoroughly developed and validated bioanalytical assay. Assay development and validation are crucial because these methods are primarily responsible for analyzing proteins, peptides, and drug compounds and their metabolites in biological matrices such as blood, plasma, serum, and urine.
Bioanalytical assay validation ensures that the assay of interest is adequate for conducting studies in the drug discovery and development process. Assay method validation further provides vital data related to the efficacy and reliability of bioanalytical studies. As assay development and validation lay the foundation for accurate analysis, sponsors constantly need tools that can further support assay development. Biomarkers are one such emerging tool for robust bioanalytical assay development and validation. Let us dive deep into how biomarkers can help develop and validate assays and explore their role in different phases of a drug development process.
Biomarkers for assay development and validation
Biomarkers are widely used as surrogate endpoints in drug discovery and development. These endpoints include exploratory, primary, and secondary endpoints and can be used while developing and validating bioanalytical assays. Exploratory biomarkers are usually standard panels assessing a specific safety signal or early efficacy signals. Primarily endpoints are often safety signals and sometimes related to efficacy factors, such as in Phase I clinical trials. Alternatively, secondary endpoints are usually the pharmacokinetic properties of a drug product.
Regulatory bodies have specific expectations with biomarker assays in clinical trials. In 2018, the FDA introduced a Fit-for-purpose approach for the development and validation of biomarker assays. This approach suggests that the level of validation will depend on the intended use of the biomarker. For instance, studies producing data for regulatory submission will need a fully validated assay. Contrarily exploratory studies for internal assessments will not require a rigorous assay method validation.
Biomarkers can sometimes be used only for exploratory studies, such as while making internal decisions or for research purposes. These assays may detect just the presence or absence of a cytokine and thus require partial assay validation. Besides, most early studies focusing on tolerability and safety need early clinical efficacy readouts. In such cases, sponsors may measure a specific biomarker and correlate it to therapeutic levels.
On the other hand, assays with a secondary endpoint will require a full method validation. A full assay validation needs robust bioanalytical methods with adequate development and validation to provide sensitive and selective analysis of study compounds. Moreover, they should be supplemented with well-developed reference standards and experimental controls.
Conclusion
Bioanalytical assay development and validation is an evolving space. Sponsors constantly search for tools and solutions to support the development and validation of bioanalytical methods. And biomarkers have emerged as a promising solution for alleviating substantial barriers in assay development and validation.
