Why Context Matters in Validating Biomarker Assays for Bioanalysis

To learn more about how method validation is performed for biomarker bioanalysis, Pharmaceutical Technology® spoke with Steve Lowes, senior director of Scientific Affairs at IQVIA Laboratories, as part of our coverage of AAPS PharmSci 360 2025.

Biomarker assays should be established and validated depending on how the data are being used, according to Lowes. “A fixed set of generic a priori criteria, as has served us well for drug pharmacokinetic bioanalysis, is just not appropriate for biomarkers due to the variances in the purpose of the biomarker data itself, and subsequently the required performance of the asset,” Lowes explains.

“Recently, this has been encompassed in the philosophy of context of use, and there are well-respected publications that walk us through such strategy,” Lowes says. “But fundamentally, you still need to understand your asset in terms of accuracy, precision, sensitivity, selectivity, and stability of the biomarker during analysis and indeed the reproducibility of the data that has been generated. An inherent challenge of biomarkers, of course, in comparison to say the xenobiotic drugs, is the endogenous presence of the analyte in the biological matrix.

“All bioanalytical assays need to be validated in the biological matrix representative of a study sample. Essentially matrix parallelism needs to be demonstrated to show that the control matrix used for calibrators and quality control, represents study samples in terms of its influence on that quantitation. There are now well described approaches to demonstrating matrix parallelism that can be found just with a simple literature search.”

Lowes stresses that one should be aware of the regulations and standards for bioanalytical method validation but should “characterize them during validation and ensure they meet the intended use of the data.”

Steve will be monitoring the Rapid Fires: AI/ML in Bioanalysis session on Monday, Nov. 10, 2025 at 3PM CT at AAPS PharmSci 360 2025, being held Nov. 9–12 in San Antonio, Texas.

About the speaker

Steve Lowes is Senior Director, Scientific Affairs at IQVIA Laboratories. Steve has 30+ years’ experience in bioanalysis with a focus on LC-MS and regulatory aspects and has been with the legacy LC-MS regulated bioanalytical lab of IQVIA Laboratories in Ithaca, NY since 1995. He is a regular presenter and author of publications on regulated bioanalysis, is co-editor of the text “Regulated Bioanalysis: Fundamentals and Practice,” and is the primary contributor to the popular Fit the Curve bioanalysis blog from IQVIA Laboratories. His most recent interests are the application of LC-MS to regulated bioanalysis of biologics and biomarkers. He received his bachelor’s degree in Analytical Chemistry at Sheffield Hallam University in the UK (1987) and a PhD in Biochemistry from the Open University, Milton Keynes, UK (1991).