Exploratory Biomarker Assays & Validation: Evolving definitions of Fit-for-Purpose and Context-of-Use (COU)

Biomarker assay development is essential for creating a robust bioanalytical method for quantifying a specific response in a chosen matrix. A biomarker ligand binding assay needs to be validated for the clinical studies in drug development. The adoption of biomarkers is impeded by the limited experience of the interpretation of biomarker data. 

Extreme challenges of authorising biomarker assays follow an integrated approach irrespective of assay validation guidelines for bioanalytical assays. This is because of a lack of standard references. A vague understanding of a biomarker’s biological aspect, like isoforms, protein truncations, modifications in the biomarker with anomalies, and deficiency of specific samples interfere throughout the assay development. 

It is therefore vital that biomarker assay developmentis suited for the intended purpose. Having a single type of biomarker assay and validation is not appropriate. A disparity in covering the spectrum of possible biomarker assays and their use led to the development of a more practical and iterative fit-for-purpose approach. 

This biomarker method development and validation approach keep the intended use of the data and the attendant regulatory requirements in mind. The sample analysis within this context of fit-for-purpose method development and validation helps in successful biomarker implementation, allowing increased use of biomarkers in drug development.

Fit-for-purpose can be defined as a conclusion that the validation level associated with a medical product development assay is sufficient for supporting its context of use (COU). Context-to-use addresses the context in which assay data is utilised. 

To ensure data integrity and reproducibility, which are fundamental to each clinical trial's success, there is a requirement for fit-for-purpose biomarker validation and assay characterisation depending on expected context-of-use. This is important for the US FDA and other regulatory agencies. 

Fit-for-purpose validation helps identify the best strategy for protein biomarker assay—the spike in personalised medication. The two concepts help biomarker assay testing services decide whether a biomarker assay can be qualified and validated when used in conjunction.

Biomarker assay and validation based upon fit-for-purpose validation practices may bring variations either because of organisational practices or due to various challenges involved. However, technical experts take the lead to determine what establishes a COU-related fit-for-purpose validation. Generally, in biomarker assays, there may be a lack of assay performance data using endogenous samples. 

The standard curve and quality control (QC) samples are analysed by employing purified recombinant or synthetic protein. A dependable biomarker testing service generates reproducible and accurate data with fit-for-purpose validation for meeting the goals of the investigation. 

Bioanalytical companies use a fit-for-purpose or custom biomarker development in consultation with biomarker lab experts who determine the analytes of interest, quantity, sample matrix, and assay platform. An initial run constituting a standard curve and QC samples is performed to assess project feasibility with the desired dilution. 

Once a method is developed, and the protocol is optimised, biomarker validation services measure bioanalytics parameters in the context-of-use. With this, bioanalytical companies ensure that the fully validated and robust biomarker assay is reliable.