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16 Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 P h a r mTe c h . c o m value of the monographs emerges with the approval of subse- quent generic versions, helping to ensure consistent quality, es- pecially as the availability of the product grows across today's global supply chain. It is here that the ultimate value for pa- tients is realized, with the quality standard in the monographs for the drug substance and product applying to all companies. Biologics and vaccines. There is, perhaps, even less agreement throughout the industry on the value or benefit of mono- graphs for biological products and vaccines. The pharmaco- poeias, and in particular the European Pharmacopoeia (Ph. Eur.), have published monographs for some biologicals since the 1990s, including human insulin, somatropin, interferon, erythropoietin, and vaccines (9). For vaccines, there are typi- cally only a few manufacturers for a specific product, limiting the applicability of the monograph to these companies. De- spite this, the public quality standard contained in the vac- cine monograph can be beneficial to regulatory agencies and medicine control laboratories involved with batch release of the product. For other, simpler biological products, including peptides and some proteins, the size and structure of the mate- rial itself can often be well-characterized by the tests typically listed in a monograph, which would be applicable to multiple manufacturers for these products. For more complex biotherapeutic products, in particular monoclonal antibodies (mAbs), the greater complexity of the material and the associated challenges in product development and manufacture create potential challenges in the develop- ment and application of quality requirements in product-spe- cific monographs, especially as the number of companies working in this area continues to grow. There is concern that specific monographs cannot be considered as minimum re- quirements for acceptability of "similar" biological products, risking the false assumption of product equivalence. This is in conf lict with regulatory guidance and patient safety con- siderations. Even while the pathways for regulatory approval of biosimilar products continue to evolve around the world, there is ongoing debate regarding the applicability of specific monographs to these complex products. The pharmacopoeias are also considering different approaches to public standards for complex biotherapeutic products, with the Ph. Eur. and Chinese Pharmacopoeia (ChP) developing product-specific monographs, while the British Pharmacopoeia (BP) and the United States Pharmacopeia (USP) are exploring alternate approaches to quality control, including the establishment of performance-based standards (10, 11). The perceived value of specific monographs by a particular company will likely guide the company's willingness to par- ticipate in monograph development. Given the broad range of products across the bio/pharmaceutical industry, it should be noted that the focus of this article is on small-molecule drug substances and drug products and the development of new monographs for these materials. The concepts and ap- proaches, however, may also be applied to the development of monographs—whether new or revised—for the broader industry, including over-the-counter medications, dietary supplements, herbals, traditional medicines, and excipients. The information provided here may also be extrapolated to the development of new and revised general chapters in the pharmacopoeias. Benefits of proactive engagement to develop monographs Pharmacopoeias are embedded in the legal and regulatory framework in countries around the world (1, 3). Pharmaco- poeias contain monographs for specific drug products and ingredients, which serve as the public standard, providing minimum quality requirements that all manufacturers must meet for the material. An end-to-end compendial framework was provided in the second article of the series to aid in understanding the range of activities that may be carried out by the compendial affairs function within a company to help ensure pharma- copoeia compliance (2). The upstream strategic activities in the process were termed "proactive compliance" and included participation in the development of new monographs in the pharmacopoeias. Bringing together the history, the regulatory and legal framework, the need for a company to comply, and the op- portunity for proactive engagement with the pharmacopoe- ias, there is one fundamental consideration to keep in mind: monographs happen. This simple truth conveys the reality that monographs will be developed and published by the pharma- copoeias whether a specific company chooses to participate in the process or not. Foundational to any company's compendial process is the strategy it chooses to follow with monograph elaboration. This critical strategy decision affects resourcing of the compendial function, because it can require significant resources to elabo- rate a monograph. The decision also determines if a company is going to be proactive or reactive in its approach to the de- velopment of compendial standards. There are pros and cons for a company to consider with each approach. Proactive approach. The reasons to proactively participate in monograph elaboration include the ability to inf luence the outcome of the public standards that are developed. For an innovator company in particular, the submission of mono- graphs is part of a strong advocacy program that brings the company's knowledge and experience to bear for its product. Proactive participation should result in a monograph that has minimal impact to the innovator company, because the core quality standards contained in the monograph should closely align with the requirements in the approved drug product registrations. The resulting standards in the monograph for a drug substance can be used for multiple product formulations and dual-active products. Proactive engagement in the monograph development process helps build a strong collaborative relationship with the pharmacopoeia authorities and enables those involved in compendial activities in a company to become acquainted with individual scientists at the pharmacopoeias. This in- Pharmacopoeia Compliance Series