Supporting preclinical and clinical studies through innovative biomarker analysis and solutions: Insights from a recent Japan symposium (Part 3)
Effective drug development is driven by robust clinical trials, which depend on collecting and analyzing individual biomarker data. Biomarker analysis is key to developing targeted, personalized therapies. However, given the diverse types of biomarkers and their context-dependent performance, validating biomarkers is still complex. Innovative solutions can help support biomarker analysis through a fit-for-purpose approach based on the context of use (CoU). Recently, at the Japan Symposium 2023, Dr. John Mu, head of immunology and immunotoxicology at Labcorp Early Development Research Laboratories, and Dr. Christopher Cooper, manager of science and reporting for immunotoxicology at Labcorp, discussed the considerations of biomarker analysis and CoU in delivering appropriate interpretation for preclinical and clinical studies at the symposium.
Why is CoU an important consideration?
Applying CoU to biomarker validations generates more meaningful data. CoU influences technology selection as well as assay design. It also defines validation criteria based on factors such as study population, sample type and testing environment. This science-based approach provides clients the right information to make decisions while clearly conveying any limitations. The two case studies below presented by Dr. Cooper and Dr. Mu describes our innovative approaches.
Case study: ELISpot validation for gene therapy
Labcorp supported a human interferon-gamma enzyme-linked ImmunoSpot® (ELISpot) validation to assess T-cell response to an adeno-associated virus gene therapy vector. ELISpot was chosen for its superior sensitivity in detecting single-cell cytokine secretion. While we achieved the required performance, high inter-individual variability meant we couldn't define a fixed cut point to determine a positive or negative response. Instead, we used a floating cut point with a donor-specific correction factor. This case showcases our fit-for-purpose approach based on CoU.
Case study: Validation of receptor occupancy assays
We worked closely with a client to support the validation of a receptor occupancy (RO) assay from their preclinical to clinical studies. As with all methods utilized in drug development, validation plans for RO assays must consider the intended use of the data and follow a fit-for-purpose approach specific to flow cytometric methods. The sample-stability period in such trials is often as short as 48 hours, making it a challenging task for logistics teams. Labcorp, however, was able to maintain sample stability and deliver reliable high-quality data. We considered factors such as cell population and receptor expression, which can affect the data quality. Conducting assay development and validation during preclinical testing can save two to three months during clinical trials. The RO assay data also provided valuable reference information to aid clinical data interpretation. This case demonstrates our specialized expertise in translating biomarker assays.
Innovation in biomarker analysis
At Labcorp, we understand the importance of biomarker assays in accelerating drug development. To support our client's development programs, we provide innovative solutions through new technologies such as digital polymerase chain reaction for gene therapy support and advanced flow cytometry for receptor occupancy studies. And notably, applying CoU helps us generate biomarker insights tailored to clients’ needs.
With six central lab facilities spread across four countries, and each lab sharing standardized equipment and operating procedures, Labcorp enables quick and seamless transfer methods between labs when supporting international trials. Our scientists have specialized expertise in immunology and immunotoxicology and work among cross-functional teams, equipping us to provide specialized support.