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22 BioPharm International eBook March 2020 www.biopharminternational.com Regulatory Sourcebook Pharmacopoeia Compliance Series One reason given for proactive participation and earlier submission of a monograph was the possibility of prospective or informal harmonization across multiple pharmacopoeias. It is instructive to take a closer look at this harmonization process. Some practical aspects of following the process to develop harmonized monographs are discussed in the companion article on BioPharmInternational.com, which can be accessed by clicking here. Historically, the development of a new monograph began with the submission of information by a company to one pharmacopoeia. This information would include specifications (e.g., the list of tests, reference to analytical procedures, and acceptance criteria), as well as select details contained in product development reports, method validations, and drug product registrations. Typical timing for the initiation of the monograph elaboration was driven by requests from the global pharmacopoeias, resulting in submissions going first to either the United States Pharmacopeia (USP) or the European Pharmacopoeia (Ph. Eur.). Later, perhaps several years later, the same information would be provided by the company to the other pharmacopoeia, which had not been part of the original submission. Even later, the information would potentially be provided to additional pharmacopoeias, including the British Pharmacopoeia (BP) and the Japanese Pharmacopoeia (JP). One practical outcome of this sequential approach to monograph development was that the resulting standards would often differ, sometimes in significant ways, regarding methods and limits that were listed in the monographs of the different pharmacopoeias. Recognizing the compliance challenges resulting from divergent standards contained in the various pharmacopoeia monographs for a particular material or product, the industry partnered with the pharmacopoeial authorities in a pilot project to develop "prospectively harmonized" monographs in the USP and Ph. Eur. The approach taken was to submit the necessary information and materials (samples and reference standards) to both USP and Ph. Eur. at the same time, with collaboration among the participants throughout the monograph elaboration process. The industry perspective on the details of this prospective harmonization approach was provided in an article published in the USP and Ph. Eur. pharmacopoeia forums (1, 2). With JP as an interested observer to this new approach for monograph development, the industry article was also translated into Japanese and published in the JP forum (3). The work was also shared with the authorities of other pharmacopoeias, including BP, the Indian Pharmacopoeia (IP), the Korean Pharmacopoeia (KP), and the Chinese Pharmacopoeia (ChP), through individual discussions and presentations at the Global Summit of the Pharmacopoeias (4). The outcome of the initial pilot project was the publication of four new monographs for drug substances that were prospectively harmonized in the USP and Ph. Eur. However, the conclusions published in a press release from the pharmacopoeias pointed to the difficulty posed by the coordination of the monograph development work between the pharmacopoeias using the formalized process that had been established (5). They determined that achieving pharmacopoeia harmonization remained an important goal, and both organizations were fully committed to continue collaboration on prospectively harmonized monographs, but this would be done using an "informal harmonization" approach. Prospective/informal harmonization of pharmacopoeia monographs Collaboration…then Expansion Scope: APIs and Products USP KP JP IP Ph. Eur. + BP ChP Secondary Work: PDG, MOUs, Observers GPhPs (Adopt / Adapt) Bio/ Pharmaceutical Company FBras SP RF Primary Harmonization Work Figure 1. Prospective/informal harmonization: current perspective. USP is United States Pharmacopeia. FBras is Brazilian Pharmacopoeia. KP is Korean Pharmacopoeia. IP is Indian Pharmacopoeia. ChP is Chinese Pharmacopoeia. JP is Japanese Pharmacopoeia. SP RF is Russian Pharmacopoeia. GPhP is Good Pharmacopoeial Practices. FIGURES COURTESY OF THE AUTHOR.