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Biotech and the United States Pharmacopeial

The United States Pharmacopeial Convention (USP) was started in 1820 as a nonprofit company with a mission to improve the health of people around the world through the development of public standards and related programs.  The end goal is to help ensure the quality, safety, and benefit of foods and medicines.  USP has pushed for the establishment public standards to the benefit of consumers by: 

• Ensuring a consistent approach to quality for innovator and generic products.
• Assessing the quality of drug products in commerce.
• Providing specifications that new manufacturers can target.
• Monitoring for counterfeit and substandard products.
• Monitoring the quality of imported drug products.
• Providing information for compounding pharmacists.

While they have always worked to establish public standards, the USP wanted to strengthen its relationship with the FDA and other public and private stakeholders and explore frameworks that would enable it to provide and maintain “up-to-date” national standards for legally marketed drugs and excipients in the United States. To meet that goal, the USP set up a group of committees to improve their role.

The USP has two different expert committees responsible for biologic and biotechnology products. The Biologics and Biotechnology 1 (BB-1EC) committee is responsible for developing monographs for glycosaminoglycan, peptides/hormones, enzymes, therapeutic proteins, and monoclonal antibodies. The plan for this committee over the next five years is to update several existing monographs and chapters, draft a new monoclonal antibodies (mAb) product class quality attribute chapter, as well as, develop new product specific monographs and reference standards.

The Biologics and Biotechnology 2 (BB-2EC) committee is responsible for developing monographs for vaccines, cell-based therapies, plasma derivatives, tissue therapies, gene therapy, and potency assays.

Monographs are used to clearly define identity, strength and purity, as well as other important quality attributes at the product level. They also allow independent testing and verification based on a public standard. The FDA works with the USP on its monograph development. The USP contains standards, specifications and other requirements relating to drugs and other articles used in medical and pharmacy practice that may be enforceable under various statues. A drug recognized in the USP-NF (National Formulary) must meet all compendial standards or it will be considered adulterated and/or misbranded. Similarly, a drug is considered misbranded and/or adulterated if it is not recognized in the USP-NF.

The last committee is the Biological Analysis Expert Committee (General Chapter), responsible for developing broad standards that apply to a large group of biological products and collaborating with BB-1EC and BB-2EC. The General Chapter provides general guidance on various aspects of monoclonal structure, function, manufacturing and control, while also establishing the minimum quality standard to which all monoclonal antibodies should adhere.  Additionally, it creates a flexible approach to defining the quality attributes and tests required to assure a minimum level of quality, since there are unique attributes of each monoclonal antibody.

Biotech products are very complex, sensitive, heterogeneous mixtures of protein molecules. Each molecular entity of that mixture is characterized by specific physical, chemical and biological properties. Specifications need to be set for each biological product based on its unique manufacturing and clinical development experience. Acceptance criteria for quality attributes in a product specific monograph would need to be exceedingly broad to capture the likely range of differences in quality attributes. Compendial tests may not account for all likely quality attributes and impurities resulting from different manufacturing processes for biological products. 

Products are divided into chapters based on different things, some of them being the scope and purpose of the product. The purpose of these product class chapters is to establish consistency in characterization of critical quality attributes across products in the same class, as well as to develop analytical methods suitable and necessary to demonstrate quality.  Current product classes under consideration by USP for chapter development include monoclonal antibodies, enzymes, vaccines, and peptides. Chapters above 1000 include general information and best practices and chapters below 1000 include procedures with performance criteria and system suitability standards.

The USP is strengthening their relationship with the FDA to improve biologics and biotechnology. By forming expert committees the USP has set a standard for product quality while keeping information and monographs current and accurate. The USP and FDA are on a road to a long term partnership which should benefit the entire Life Science industry.

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