Large Molecule PK Assays: Optimizing Bioanalysis For Preclinical Through FIH

During drug development, a fluid transition from preclinical research to clinical trial is key for generating high quality, decision-critical data while adhering to budget and timeline. However, bioanalytical differences in focus and scale between preclinical and clinical investigations can make this changeover a challenge.

Preclinical studies are designed to evaluate whether a compound has the potential to move from lab to bedside. During this phase, understanding the drug’s safety and toxicity is the primary goal. Typically, large dosages of the compound are administered to laboratory models to generate preliminary data. Even though multiple animal models are often tested, the preclinical phase has a relatively short duration.

In contrast, the clinical trial journey is long and has a broader focus: not only safety, but also, efficacy. In order to prevent clinical incidents and minimize clinical size effects, these studies must progress stepwise from low drug dosages and small subject pools to higher dosages and greater numbers of subjects. Ultimately, a large cohort is required to make statistically valid conclusions regarding drug safety and efficacy.

Because of these differences in scale and purpose, many preclinical assays are not suitable for transfer to clinical studies. During the clinical stages, careful planning is required to select appropriate assays and prevent unnecessary roadblocks and delays.

In this article, the key parameters (e.g., assay design, matrix interference, assay sensitivity and assay range) of preclinical and clinical assays are compared. Recommendations are then provided to facilitate the transfer of assays from preclinical to clinical phases, whether that means optimizing the preclinical assay, redeveloping the assay or changing the assay platform altogether to perform as needed for clinical development.