Biomarkers are used widely in the drug development and discovery process. Irrespective of the stage of drug development, biomarker testing has become a vital necessity. But what is the drug development process? Drug development aims to identify possible compounds that can safely and effectively treat disease and medical conditions. Hence, a significant discussion is needed on the context of use so that all relevant stakeholders clearly understand the data, assay purpose, and clinical decisions.
A timely discussion between biomarker CRO and the end-user in the drug development process will facilitate the development of suitable biomarker assays. Hence, the current article focuses on the prime considerations for biomarker testing services and biomarker assay validation. Moreover, additional details are provided for a robust biomarker assay development and validation.
Types of test biomarker assays
Although PK analysis has well-defined regulatory guidance, biomarker development, and validation lack clarity. Biomarker assay are not similar to PK assays. PK assays have a well-developed and characterized calibrator material as a standard. However, most biomarker assays often don’t have a calibrated standard to compare the study results. Generally, biomarker assay services employ a synthesized or recombinant standard. Biomarker assays can either be qualitative or quantitative. Besides, the quantitative assay can further be classified as relative, definitive, and quasi-quantitative assays. Biomarker assay services must consider the following assay pillars for biomarker validation and development.
- The phase of drug development required for analysis
- Anticipated or observed concentration changes in PD data
- Decision-making based on the generated data
- And possible assay fit with regulatory expectations.
Regulatory compliance for biomarker assays
Before 2013, bioanalytical method validation solely focused on pharmacokinetic assays. After FDA’s bioanalytical method validation in 2018, the biomarker testing industry was guided to use PK approaches for biomarker assay validation. However, the drug development industry may have overlooked a prime aspect of the bioanalytical method validation guidance. It states that the industry guidance belongs to the quantitative determination of analytes in study matrices. But it is understood that only a handful of biomarker assays fall under the quantitative determination category. Although, sponsors should also consider the fact that FDA supports a fit-for-purpose approach for biomarker method validation.
Moreover, FDA supports the context of use. The FDA suggests that studies supporting regulatory decisions will require a full validation, whereas exploratory studies may not require such stringent validation protocols. Hence, sponsors must first understand their study objective and proceed with biomarker assay validation.
The context of use
The context of use in biomarker testing may change over time. Hence, sponsors must define method development and validation early in the process. Besides, method validation confirms prior results in a controlled setting. The context of use in biomarker assays depends on the purpose of the study and thereby will dictate several factors in biomarker development and validation. Ultimately, the context of use is the core element of biomarker assays. Without a complete understanding of assay objectives, sponsors can run into issues related to suboptimal development and validation issues. Such suboptimal results will often generate inaccurate data and may lead to poor decisions in drug discovery and development projects.