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16 BioPharm International eBook March 2020 www.biopharminternational.com Eur.), have published monographs for some biologicals since the 1990s, including human insulin, somatro- pin, interferon, erythropoietin, and vaccines (9). For vaccines, there are typically only a few manufacturers for a specific product, limiting the applicability of the monograph to these companies. Despite this, the public quality standard contained in the vaccine monograph can be beneficial to regulatory agencies and medicine control laboratories involved with batch release of the product. For other, simpler biologi- cal products, including peptides and some proteins, the size and structure of the material itself can often be well-characterized by the tests typ- ically listed in a monograph, which would be applicable to multiple man- ufacturers for these products. For more complex biotherapeu- tic products, in particular monoclo- nal antibodies (mAbs), the greater complexity of the material and the associated challenges in prod- uct development and manufacture create potential challenges in the development 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 requirements for acceptability of "similar" biological products, risk- ing the false assumption of prod- uct equivalence. This is in conflict with regulatory guidance and patient safety considerations. Even while the pathways for regulatory approval of biosimilar products continue to evolve around the world, there is ongoing debate regarding the appli- cability of specific monographs to these complex products. The phar- macopoeias are also considering dif- ferent approaches to public standards for complex biotherapeutic prod- ucts, 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 estab- lishment of performance-based stan- dards (10, 11). The perceived value of specific monographs by a particular com- pany will likely guide the compa- ny's willingness to participate 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-mole- c ule dr ug substances and dr ug products and the development of new monographs for these materi- als. The concepts and approaches, 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). Pharmacopoeias contain mono- graphs for specific drug products and ingredients, which serve as the public standard, prov iding minimum qualit y requirements that all manufacturers must meet for the material. A n e n d - t o - e n d c o mp e n d i a l framework was provided in the second article of the series to aid in understa nd ing t he ra nge of activities that may be carried out by the compendial affairs function within a company to help ensure pharmacopoeia compliance (2). The upstream strategic activities in the process were termed "pro- active compliance" and included participation in the development of new monographs in the phar- macopoeias. Bringing together the history, the regulatory and legal frame- work, the need for a company to comply, and the opportunity for proactive engagement with the pharmacopoeias, there is one fun- damental consideration to keep in mind: monographs happen. This simple truth conveys the reality that monographs will be developed and published by the pharmaco- poeias 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 elaborate a monograph. The deci- sion also determines if a company is going to be proactive or reactive in its approach to the development of compendial standards. There are pros and cons for a company to consider with each approach. Proactive approach The reasons to proactively partic- ipate in monograph elaboration include the ability to influence the outcome of the public standards that are developed. For an inno- vator company in particular, the submission of monographs is part of a strong advocacy program that brings the company's knowledge and experience to bear for its prod- uct. Proactive participation should result in a monograph that has minimal impact to the innovator company, because the core quality Regulatory Sourcebook Pharmacopoeia Compliance Series