As the application for biomarkers continues to increase in drug discovery and development, expedited timeframes for therapeutic products are more possible than ever. Biomarkers assist in accelerating drug development by helping to identify disease targets, better understand the mechanism of action of the drug candidate, and assess the effectiveness of the drug during the clinical trials, which not only cuts costs to the companies and teams behind them, but also allows patients to receive the life-saving drugs they need faster.

The ability to expedite processes also creates more pressure to use biomarker data to make early decisions on drug candidates, such as whether to “kill” or “save” a drug program. The need for speed brings with it the risk of overlooking pivotal factors to ensure the biomarker assay is set up to actually be of use to support the intended study. And what key consideration is most often overlooked? The answer is simple yet surprising: biology.

Biology’s Direct Impact on the Context of Use

Today many bioanalytical scientists are feeling the heat to simply validate a biomarker assay with as much sensitivity as possible. But, they often don’t know the exact context of use (COU) for the assay they must develop. Full consideration of the COU must focus on practical considerations of the assay’s design, such as: who is the patient population? What are their specific characteristics in terms of age, gender, and ethnicity? Are there patient population comorbidities? How will the samples be acquired?

This is because there is no doubt that our genetic makeup is different. Transcription factors that turn our genes “on” or “off” vary from person to person; the presence or absence and/or the level of many proteins in our bodies vary; and our age, the environment we live in, what we eat, and even how much we exercise dictates our biomarker levels. Therefore, we need to always keep in mind that “Biology Matters” and ask the appropriate questions to help determine the performance characteristics for the assay early in its design process. This will help guide the development of an assay that can meet the intended study’s specific objectives and the biomarker’s intended purpose.

Biology Impacts Fit-for-Purpose Validation Too

Fit-for-Purpose (FFP) is defined as a conclusion that the level of validation associated with an assay is sufficient to support its context of use. As discussed by Lee et al. (2006), the FFP status of a biomarker method is deemed acceptable if the assay is capable of discriminating changes that are statistically significant from the intra- and inter-subject variation associated with the biomarker.

For example, an assay with 40% total error allowable determined during validation may be adequate for statistically detecting a desired treatment effect in a clinical trial for a certain acceptable sample size, but this same assay may not be suitable for a clinical trial involving a different study population that has much greater physiological variability. Again, “Biology Matters” in setting up acceptance criteria.

Accounting for Biology in Our Bioanalytical Processes

A hallmark of BioAgilytix’s biomarker assay development and validation services is that we work to understand the intended use of the assay in our earliest discussions, and in particular, learn as much as we can about the patient population that will be taking part in the clinical trials. It is this attention to detail and level of awareness that drives proven, high-quality results that stand apart among biomarker service offerings worldwide, enabling us to deliver the best assay solutions for each customer’s unique study and specific patient population.

BioAgilytix and Biomarker Assay Validation

The importance of biology in biomarkers development and validation is just one topic among many in the field of biomarkers. In our upcoming blog series, we’ll be discussing biomarkers in all of their facets, ranging from biological underpinnings to other contemporary and futuristic topics. In the meantime, you can learn more about our biomarker services here, or schedule a discussion with our scientists to talk through your biomarker needs and how we can support them.