Biomarkers play an important role in disease identification and have now gained a more comprehensive role in drug discovery and development. The primary function of a biomarker in drug development is to facilitate early and robust drug efficacy and safety measurements. For a biomarker to take its rightful place in drug discovery and development, bioanalytical companies should focus on understanding disease mechanisms and therapeutic intervention, along with biomarker study validation and application. To understand the complete picture of pharmacodynamic biomarker drug development and biomarker discovery, let us explore each of its facets.

Biomarkers representing disease mechanisms

By definition, biomarkers should associate with the mechanism of a disease. Early during biomarker drug development and biomarker discovery, a biomarker assay should try to review the theoretical mechanism of a disease, which could later be banked upon to illustrate the disease mechanism in the development phase.

An ideal biomarker assay should be able to identify fundamental molecular and biochemical alterations occurring in disease progression and therapeutic interventions. Even if a biomarker does not become a surrogate clinical endpoint, it should at least provide radical insights into the disease mechanism during early bioanalytical studies.

Inputs for pharmacokinetics and pharmacodynamics modeling

Pharmacokinetics (PK) and pharmacodynamics (PD) are two decisive characteristics of drug/body interactions. In simpler terms, PK assesses how the body reacts with the drug, and PD assesses how the drug reacts with the body. PK/PD data help bioanalytical companies gain deep insights into the relationship between drug concentrations and their effects on the body. Biomarker assays provide great value by facilitating inputs and early decision-making for PK/PD modeling. PK/PD models should not be more complex than needed and should comprise only the mechanism-based and rate-limiting components of the study structure.

Importance of selecting an appropriate biomarker assay method

Bioanalytical companies primarily use binding assays or chemical assays for biomarker method validation and biomarker assay development. Compared to general drug assays, biomarker assays are more complicated. Biomarkers are made of distinct complex molecular structures. These structures range from simple amino acids and electrolytes to vast proteins and whole microorganisms such as bacteria and viruses. Thus several factors contribute to biomarker assays’ complexity.

Therefore, for a bioanalytical company, it is difficult to validate a biomarker study by following good laboratory practices.

Bioanalytical companies consider key steps while selecting an appropriate biomarker assay method. The first step is to identify a suitable and meaningful sample matrix for the biomarker study. Bioanalytics prefer accessible matrices such as a serum, plasma, and urine to samples that are difficult to get, such as biopsies. Another aspect of biomarker assays is to obtain analyte-free/biomarker matrices for preparing calibration standards and validate performance similarity between both the authentic and non-authentic matrices.

Biomarkers are present in both heterogeneous and varied bound states. Therefore, instead of definitive quantification, bioanalytical companies use relative quantification approaches that provide some leniency in accuracy and rely on reproducibility, precision, and robustness of the biomarker assay validation.

Opportunities in biomarker drug development and biomarker discovery

The future of drug development bioanalysis lies in the optimum utilization of biomarker assays. Although preclinical biomarker studies will help in establishing a foundation for clinical models, only augmenting on this foundation can help in the development of a drug and its smooth transition from clinical trials to the marketing phase.