Assay development is foundational to the well-characterized biotechnology product paradigm. Bioassays are the best tools for drug developers to use in determining the biological activity (potency) of their products, which has been a biopharmaceutical critical quality attribute (CQA) since long before that concept had a name. Thus, these assays are vital to quality assurance and quality control (QA/QC), preclinical studies, and clinical testing — and by extension to process development and monitoring. Yet because of their complexity, bioassays are among the most challenging experiments to perform reliably with dependably accurate results. Consistency requires a controlled environment and qualified reagents, skilled analysts, and assay protocols that are intelligently developed, characterized, and validated. Depending on the use of a method, it could be required to comply with good laboratory practice, good clinical practice, or good manufacturing practice (GxP) regulations as well as electronic data security. This featured report explores how emerging technologies, including systems that enable automation, simultaneously could facilitate and complicate bioassay development and execution.

Introduction: Technologies Converge in Biopharmaceutical Laboratories
by Cheryl Scott
Making automation systems work together for reliable assay execution can be a specialty in itself. BPI’s senior technical editor speaks with Milena Stanković-Brunnera of Synthace Limited in London, UK, to explore challenges that QA/QC teams will face when implementing and integrating laboratory automation systems. The discussion also broaches the increasing importance of biostatistics in biopharmaceutical experimental design and the subsequent need for software that facilitates design of experiments (DoE) approaches and data collection and analysis.
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Automation of Potency Assays: A Strategic Journey
by Maribel Rios and Cheryl Scott, with Hermann Beck
At the CASSS Well-Characterized Biotechnology Products (WCBP) conference in May 2019, Hermann Beck (F. Hoffmann-La Roche) presented an approach to automation of potency assays under the rubric of “It’s not plug-and-play; it’s a journey.” In 2020, BPI’s managing and senior technical editors spoke with Beck to discuss the topic further. Beck herein explains that although automation is used often for high-throughput tasks such as screenings and diagnostics, automation of bioassays for QA/QC operations might not always make sense. Thus, automation should be considered strategically, ultimately balancing the costs and processes needed to implement automation systems with laboratory needs.
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HCP Assay Development: Managing Risks with Evolving Technologies
by Cheryl Scott, with Denise Krawitz
Removal of host-cell proteins (HCPs) from drug substances is critical in manufacturing high-quality drug products, and a well-developed, broadly reactive, and qualified HCP immunoassay is vital to such analyses. How well a particular assay recognizes all HCPs will depend on how well its antibodies recognize the actual HCP profile. Such antibody preparations ideally would react with all potential HCP impurities, but it is impossible for any single assay to suffice in all cases. Understanding available HCP assay methods can help biopharmaceutical analysts implement a coverage strategy that optimizes accuracy, minimizes safety risks, and prevents product-approval delays. In January 2021, BPI’s senior technical editor interviewed Denise Krawitz (CMC Paradigms) to explore emerging topics and trends in HCP assay development, including the increasing application of liquid chromatography– and tandem mass spectrometry (LC-MS, MS-MS) workflows, advances in process analytical technologies and software, and challenges with setting criteria for HCP abundance.
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Stability Testing: Monitoring Biologic Product Quality Over Time
Cheryl Scott, with Nadine Ritter
Industry consultant and long-time BPI editorial advisor Nadine Ritter herein explores considerations for stability assay development. After contextualizing the complex interrelations of potency, lot-release, and stability assays, she describes what kinds of stability testing occur at each part of a biopharmaceutical’s lifecycle — and how information from each stage influences later assay design and processing. Ritter also calls attention to special analytical requirements for novel modalities and gives an update on technical and regulatory developments relating to bridging methods for release and stability testing.
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