Pharmacokinetic (PK) and toxicokinetic (TK) bioanalysis presents challenges at all stages of development for the safety and efficacy of biologics. Early in development, there is a need to support multiple therapeutic candidates and multiple programs. Preclinical development is subject to aggressive timelines and large sample numbers in a variety of species with limited volumes for both samples and reagents. In regulated bioanalysis, more robust methods with higher throughput and assay precision are essential for decision making in compressed project timelines. Application of Gyrolab technology for PK and TK bioanalysis provides versatility and flexibility at all stages in an automated, nanoliter-scale format.
Three full PK profiles from three rodents; IV administration of a therapeutic antibody.
(Data courtesy of AstraZeneca)
Gyrolab immunoassays supporting pharmacokinetic studies offer benefits in sample volume, assay time, and broader dynamic ranges compared to ELISA and other plate-based methods:
In biotherapeutic discovery and development, a flexible assay design is critical to support multiple species and programs with large numbers of samples, conditions and limited reagents. Gyrolab Generic PK assays allow for a platform approach to quantitate multiple human mAbs in animal sera, increasing automated throughput capacity for proof of concept and rapid assessment of lead candidate identification and optimization. Where a specific PK assay development is needed, Gyrolab immunoassays dramatically reduce assay development time from weeks to days, since multiple assays and conditions can be run in parallel or on different segments within the CD consumable. Gyrolab Generic TK Kits are based on the same reagents as the PK kits but use different Gyrolab Bioaffy CDs that differ in sample volume to shift the concentration ranges higher, meeting the higher dosing requirements for TK studies.
The nanoliter volume requirements of Gyrolab systems enable researchers to obtain an entire PK from a single mouse which significantly reduces the number of mice used and the biological variability of PK endpoints. Obtaining a PK profile from a single mouse using serial sampling is an animal sparing strategy consistent with the 3R research initiative that has been established at multiple biopharmaceutical companies with the Gyrolab platform. This strategy reduces the number of mice needed by 60-80% which not only improves data quality but impacts cost reductions in maintaining animal colonies, husbandry needs/facilities and removal of biological wastes. The ability to execute a one mouse, one PK profile strategy on Gyrolab platforms is especially useful when test articles are in short supply, rank ordering of PK with more than three test articles and with rare animal disease models.
Regulated bioanalysis in support of GLP compliant preclinical and clinical PK studies require increased method robustness and reliability as these assays are continually validated and used for long-term study support. Automation of PK bioanalysis on Gyrolab platforms provides higher throughput, minimal staffing, faster analysis time, while reducing the manual sources of error also improves overall method robustness and facilitates assay transfer to CROs. Since reagent use is greatly reduced, validated reagent batches can be stretched for the duration of the study, avoiding the need to re-validate new reagent lots.
To hear what success looks like for one of our customers, Read the interview with Shawn Fernando, Morphotek Inc., on high-throughput PK assays in Phase II/III trials.
Want to learn more? Speak to our scientists about your application.