PK/PD assays play a crucial role in drug development. PK/PD analysis can identify in vivo drug properties that allow researchers to characterize and predict drug characteristics under pathological and physiological states. Today, evaluating PK/PD properties has moved from a descriptive approach to a mechanism-based evaluation. This approach considers the causal path between drug effect and drug administration.
Recent advancements in systems biology and pharmacology are providing newer insights into drug complexity. This understanding has given rise to opportunities for testing new drug combinations that can only be developed with adequate data from PK/PD assays. On the other hand, bioanalytical solution providers are focused on bringing new and reliable biomarkers with a broad utility in healthcare and research settings. Indicators such as PK biomarkers provide measurable data about specific biological states. Moreover, for example, blood glucose levels are used to monitor diabetes, whereas tumor biomarkers can help diagnose cancer and develop therapies. Hence, the current article focuses on advances in PK/PD analysis and the importance of biomarkers in drug development.
Advances in PK/PD assays
The primary goal of PK/PD analysis is to identify in vivo drug properties. Earlier PK/PD modeling had an empirical approach consisting of the pharmacokinetic model, the pharmacodynamic model, and a link model that assesses the delayed drug effect in plasma concentrations. These models have been crucial in developing drug products. However, targeted distribution kinetics for drug products is more complex. These complications gave rise to physiologically based PK models.
Today, PK/PD analysis incorporates a more mechanism-based approach. This method characterizes the causal pathway between drug effect and administration. Besides, this approach includes target site distribution, pharmacodynamic interactions, binding and activation, homeostatic feedback mechanism, transduction, and disease progression. A crucial feature of this approach is the distinction between system-specific and drug-specific properties. Such an explicit description seems to be critical for assessing drug effects in vitro and animal models.
Moreover, PK/PD assay is crucial for immunogenicity assay development. Biological products may induce unwanted immune responses. Hence, ADA methods such as MesoScale ADA bridging assay and ADA ELISA assay are vital for assessing drug immunogenicity. The US FDA recommends a multi-tier approach that includes confirmatory ADA assay, drug tolerance ADA assay, and NAb assay development for testing immunogenicity. Therefore, advances in PK/PD analysis will remain crucial in developing biological drug products.
Role of Biomarkers in drug development
Bioanalytical biomarker services are constantly involved in discovering and developing novel biomarkers that can help accelerate drug development. Biomarkers have several applications in the drug development process, such as:
• Accelerating drug development for specific therapeutic areas
• Monitoring drug safety
• Determining the potential of therapeutic solutions in achieving desired results
• Predicting drug efficacy
• Potentially saving time, costs, and resources during preclinical and clinical studies
The US FDA allows including new biomarkers via two approaches: the biomarker qualification program and the drug approval process. Drug developers often integrate new biomarkers by employing the concept of context-of-use. This approach focuses on developing biomarkers that are fit for the intended application. Hence, advances in PK/PD assays and biomarker development will be vital to bring safe yet effective drug products.