Serum sample stability in ligand-binding assays: challenges in assessments of long-term, bench-top and multiple freeze-thaw.

Abstract

Chris Macaraeg has been a lead scientist for method development, validation, and study support intended for regulated pre-clinical/clinical studies within the Pharmacokinetics and Drug Metabolism department at Amgen Inc, Thousand Oaks, CA. He joined Amgen in 2006. His expertise also includes automation and method transfer to CROs. Chris received his BS degree in Physiological Science and Neuroscience from the University of California, Los Angeles, CA and MS in Forensic Science from Pace University, New York, NY. Stability of therapeutic proteins in biological matrix is an important parameter to evaluate in bioanalytical support of regulated nonclinical or clinical studies. Despite industry guidance publications, many questions still arise as to how these practices are implemented to establish therapeutic protein stability in bioanalytical method validations. This article presents findings from long-term, bench-top and freeze-thaw stability assessments for three therapeutic monoclonal antibodies using either ELISA or electrochemiluminescent technology. Studies illustrate the principles and challenges in stability tests which represent scenarios that samples will likely encounter during sample analysis. Thoughtful consideration of each study requirements and a fit-for-purpose approach is essential in successful establishment of the sample stability parameters in method validation.