Increasingly, biologic drugs are used to treat an expanding list of complex diseases and the development, monitoring, validation and revalidation of bioassays to measure their potency are critical. On Dec. 4-5, 2012, the United States Pharmacopeial Convention (USP) will host the Fifth Bioassay Workshop at its headquarters in Rockville, Md. Manufacturers, regulators and other stakeholders in the biopharmaceutical arena will present on key bioassay-related topics including the replacement of animal-based assays with cell-based approaches; USP’s documentary standards for bioassays; and software selection for bioassay analyses.
Unlike conventional pharmaceuticals that are chemical molecules synthesized through chemical routes, biologics—especially modern products such as recombinant proteins and monoclonal antibodies—are derived from living cells or organisms. Biologic drugs are also larger and more complex in their molecular makeup compared to chemical drugs, and often are heterogeneous in structure. For these reasons, it is generally not possible to fully characterize many biologics using commonly-applied and well-established analytical techniques employed in the characterization and control of chemical molecule drugs. Instead, manufacturers of biologics often rely on bioassays to monitor and maintain drug potency; to validate that a drug is continuing to work in the manner in which it is intended, usually by comparison to a known standard; and to establish stability and batch-to-batch consistency.
In August 2012, the informational “USP Bioassay Chapters”—General Chapters <1032> Design and Development of Biological Assays; <1033> Biological Assay Validation; and <1034> Analysis of Biological Assays became official. These new chapters describe the lifecycle management of bioassays for drugs, ranging from development to post-licensure stages. While the chapters have only recently become official, many manufacturers have already started drawing upon them as a resource and putting concepts from the chapters into practice. At the workshop, USP will seek feedback from attendees as to the utility and usefulness of the chapters. Additional opportunities will include understanding of chapter elements that may require further development. Assay-specific case studies will be presented. Other session presentations will include parallelism testing for biological assays; quality by design (QbD) for bioassays—from development to use; and regulatory perspectives on the development and validation of bioassays suitable for intended use.
The December workshop will also consider the role of emerging technologies. Newer technologies that can measure a molecule’s potency and are tied to its mechanism of action are important for manufacturers to consider in the development of future bioassays. Some newer assay methods that may be more precise in measurement and easier to execute in the laboratory include physicochemical tests and cell-based assays that have the potential to replace traditional animal-based approaches. In order to successfully replace animal-based assays, manufacturers must be able to demonstrate that new methods are suitable throughout the shelf life of the product and that potency values obtained with the new assay can bridge to that obtained with the previous assay and drug batches. Regulatory perspectives on the implementation of new methods will also be considered, and presentation topics include alternatives to animal testing in the quality control of erythropoietin, and a comparability study of the structure of filgrastim and mutants using nuclear magnetic resonance fingerprint assays.
Because manufacturing processes may change during the lifecycle of a biologic drug, well-validated bioassay procedures may be particularly useful to assure unchanged performance of a biologic medicine. The qualification of critical reagents and reference materials used during a product lifecycle also are important considerations Strategies for monitoring and replacing these materials will be discussed during the workshop.
The application of relevant bioassay development software will be a focus of the workshop. In an open-forum question-and-answer session, attendees will have an opportunity to interact with software vendors about their product capabilities. In addition, small group sessions with vendors will allow users to elaborate on their own in-house needs and determine how specific software offerings can address them.
A scientific, nonprofit organization, USP develops standards for the identity, strength, quality and purity of drug substances, drug products and excipients. Documentary standards are published in USP’s compendia—United States Pharmacopeia and National Formulary (USP–NF). Standards appear in the form of monographs and general chapters in USP–NF, and as companions to these documentary standards, USP also offers reference standards—typically well characterized physical materials—used for tests and procedures in USP–NF.
Release Date: Nov. 27, 2012
Filed Under: Drug Discovery