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POTENCY TESTING


Potency Testing of Biopharmaceutical Products


Weihong Wang, PhD


Technology Development Manager Eurofins Lancaster Laboratories


Submitted: 08/25/2014 Accepted for Publication: 09/02/2014 Introduction


Potency determination refers to the quantitative measurement of the biological activity of a given product. Biological activity is a critical quality attribute; therefore, potency testing is an essential component of quality control. Various procedures, including animal-based assays, ligand and receptor binding assays, cell culture-based assays, or other biochemical assays (such as enzymatic assays), may be used for potency testing based on the mechanism of action of the product. This article provides a review of the more commonly adopted assays—specifically ligand and receptor binding and cell-based potency assays, as well as recent advancements in statistical analysis for potency determination and strategies for phase appropriate method development and validation.


Ligand and Receptor Binding Assays


Dr. Weihong Wang is Technology Development


Manager for Eurofins Lancaster Laboratories’ Molecular and


Cell Biology group. She oversees assay development/validation projects and serves as a subject matter expert and direct technical contact to assist clients with testing needs. Dr. Wang has 12 years of experience developing


and characterizing biopharmaceutical products and has extensive experience with ELISA and


cell based assays. Dr. Wang earned a PhD in Cell and Molecular Biology from Brandeis University and completed postdoctoral research at Harvard Medical School.


Many biological products, such as monoclonal antibodies, exert their function via binding to a cellular or soluble target, which subsequently triggers appropriate downstream cellular events. For these products, a binding assay offers direct measurement of the product’s affinity to its intended target and may be suitable for potency testing. The most common type of binding assays is the Enzyme Linked Immuno-Sorbent Assay (ELISA), which can be developed relatively quickly and typically offers robust performance. With the advancement of technology, various “homogeneous” immunoassays have been developed and successfully utilized for potency measurement in QC settings.


Examples are Time Resolved Homogeneous Fluorescence


Resonance Energy Transfer assays, Amplified Luminescence Proximity Homogeneous assays (such as AlphaLISA) and Proximity Based Electrochemiluminescence Immunoassays.


These


homogeneous immunoassays eliminate the need for wash steps, and the simple “mix and go” procedures result in decreased assay time and potential analyst error.


In some cases, superior


signal-to-noise ratio and better overall assay performance, as compared to traditional ELISA, may be achieved. However, custom protein conjugation may be required, and assay performance is much dependent on the quality of these critical reagents (tagged proteins, donor and acceptor beads, etc).


In addition to immunoassays, Surface Plasmon Resonance (SPR) assays have also


been utilized to measure product binding to its intended target. In an SPR assay, protein-protein interaction is detected in real time through changes in mass due to adsorption at the chip surface. Data generated can be used to calculate the binding constant; therefore, SPR assays can be particularly useful during product development. To date, SPR assays have not been used as widely as QC methods for potency measurement but have been adopted sometimes for product


8 American Pharmaceutical Review | Biopharmaceutical Supplement 2014


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