(T1330-06-31) Development of Cell-Based Bioassays for Measuring the Potency of Biological Drug Products

Purpose: Bioassays are essential for the development of biopharmaceuticals as they provide critical data on the potency and stability of biological drug products, and are frequently utilized to ensure quality of manufacturing processes and for lot release testing. The purpose of this study was to develop cell-based analytical methods for measuring the potency of biological substances through their effects on living cell systems.

Methods: Cell line systems and analytical methods were evaluated and selected upon numerous factors such as cell stability, intrinsic background signal, analytical sensitivity, dynamic range of dose response, etc. Selected cells were cultured in multi-well plate format, exposed to a biological substance along with a reference standard at multiple doses. Cellular responses were measured by flow cytometry, high content imaging, and/or mass spectrometry (LC-MS) methods. The relative potency of a test biological substance in comparison to a reference standard was determined using the parallel logistic potency assay methods built in biostatistical software PLA 3.0 (Version 3.0.4, Stegmann Systems, Germany).

Results: Using a well-established bioassay, cells exhibited dose-dependent responses, data results were fitted by 4- or 3-parameter logistic model, and the relative potency of a drug product was determined with confidence.

Conclusion: Developing and optimizing cell-based bioassays is a multi-step process and involves multidisciplinary studies. Thorough evaluation of factors that influence assay performance is critical for the success of assay development.