Protein Therapeutics and the Regulation of Quality: A Brief History - As the biotechnology industry has matured through various stages of growth, regulatory agencies have evolved in response to the ne

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Protein Therapeutics and the Regulation of Quality: A Brief History
As the biotechnology industry has matured through various stages of growth, regulatory agencies have evolved in response to the need to define quality standards.


BioPharm International
Volume 20, Issue 10

The Critical Path and Biology. A key to the use of PAT, QbD, and risk management is defining critical product attributes and linking them to critical process parameters. Product complexity and heterogeneity suggest that critical product attributes can only be defined with a better knowledge of product–biology and structure–function relationships. Characterization of the in vivo structures of biotechnology products may be an important strategy to define critical product attributes. Although biological characterization is challenging, the benefits are not restricted to manufacturing and may play a role in other dimensions of the critical path for drug development. The FDA's critical path initiative was launched in March 2004 with the release of an important report entitled Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products. The Critical Path initiative includes industrialization as well as dimensions covering safety and medical utility. Biological characterization may enhance mechanistic understanding and inform decisions regarding product safety. This mechanistic understanding may also facilitate the appropriate selection of animal models. An understanding of molecular mechanisms using a variety of models can inform clinical trial design. Moreover, as the industry moves forward with the development of biomarkers and the use of systems biology (e.g., pharmacogenomics and proteomics), mechanistic understanding can provide plausibility for decisions based on complex data sets.

OBP Research Activities. The OBP staff reviews regulatory submissions for investigational new drugs (INDs), BLAs, NDAs, and supplements. The staff participates in meetings, pre-approval inspections, and some postapproval inspections. Many OBP reviewers are laboratory-based and involved in research programs. This gives OBP research programs direct access to emerging regulatory challenges. Areas of OBP research include: the development of bioactivity assay cell lines for products such as anthrax toxin therapeutics; the role of aggregates and residual host cell molecules in immunogenicity; viral clearance and inactivation studies; and the development of standards for virus retention filters. The research programs have internal and external reviews, as indicated earlier, and result in guidance and other publications, and facilitate effective sponsor interactions. Research on topics such as cytokine biology relate to the products the office currently regulates, however, an internal knowledge base in immunology, biology, and biochemistry also prepares the staff to deal with new developments.

FDA Commissioner Andrew von Eschenbach has highlighted the FDA as a bridge from discovery to delivery. To function as this bridge, the FDA must be a science-led agency. He instituted the Interagency Oncology Taskforce (IOTF) while still director of the National Cancer Institute to forge such a bridge. OBP has had multiple IOTF fellows in its research programs and intends to continue to strengthen the discovery-to-delivery bridge in whatever ways needed.


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