Cirion has extensive experience performing PK and immunogenicity assays to support preclinical and clinical trials.
“You can analyze a biomarker in a variety of ways,” explains Lorella DiDonato, Ph.D., vp of R&D. “We focus on making sure that we have a diversity of technologies to ensure that the most appropriate technology is available to perform the analysis for each biomarker.”
A major challenge, according to Dr. DiDonato, is when the sponsor does not have a clear idea of the intended purpose of the biomarker analysis—whether it is exploratory in nature or part of a clinical endpoint.
“With PK assays, the intended purpose is, in a majority of cases, a primary endpoint. At an early stage in the drug development program, the analysis of several biomarkers is often exploratory in nature since it is unclear which of the biomarkers is the key marker that will support efficacy or safety of the drug in development.
“At this stage, it is appropriate to qualify the assays and analyze the samples to evaluate the levels present in healthy versus patient populations, as well as how the levels are affected pre- and post-administration of the drug. Once a biomarker is qualified, full validation, which will be performed exactly as a PK assay, is required.
“If there are commercially available kits to perform the analysis in an exploratory analysis, we will not challenge the methodology of the kits but will evaluate in a feasibility testing whether the kits are performing according to manufacturer’s specifications. Should the results concur with the kit specifications, we will then proceed with the analysis and discuss with the client whether the results are informative.
“At this point, the list of biomarkers to analyze is reduced to just several biomarkers. We will then challenge the methodology of the kits to ensure that the assay is enhanced in terms of robustness, precision, and accuracy. We will also prepare quality controls and not use the controls of the kits. In addition, we will perform stability evaluations and not rely on the manufacturer’s stability data.”
Dr. DiDonato will talk about one instance when a commercial kit was available to perform a biomarker assay validation, but it didn’t perform as expected.
“We ended up developing an assay from scratch similar to that of a PK assay. Often the perception is that a biomarker assay, especially when a commercial kit is available, should not require the same time and cost as a PK assay. Therefore, the challenge we face is: how do you present to the sponsor that the development and validation of a biomarker assay will cost as much as if it were a PK assay, which is a primary endpoint?” concludes Dr. DiDonato.