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www.biopharminternational.com eBook December 2019 BioPharm International 35 move forward from proposal to official without significant change from what was initially proposed. In the authors' experience, 90% or more of proposed changes move forward 90% of the time with no major change to the proposal. If there are significant changes, as sometimes seen with proposals for new or significantly updated general chapters, the pharmacopoeia will typically publish another draft for review and comment before becoming official. Given this situation, the sooner a company can assess the impact of a pharmacopoeia revision (i.e., at the proposal stage), the better they are able to plan for a smooth implementation of the change, especially given the challenges associated with official change control processes in many companies. This evaluation also enables the submission of comments to the pharmacopoeia, when necessary, advocating in regard to changes that may be unacceptable or unachievable for the company. O f f i c i a l c h a n g e s : E v a l u a t e a n d p r o c e e d w i t h implementation. The pharmacopoeia process to introduce new and revised monographs and general chapters continues from the proposal stage to the subsequent publication of updated requirements that become official through new editions and supplements. The publication of these updated requirements triggers the final phase of the industry surveillance process. The specific steps performed by a company at this official stage are essentially the same as described for the proposal stage: monitor the publications, filter for impact, communicate, and evaluate the changes. The ultimate goal, however, shifts to focus on implementation. If the revision was previously evaluated at the proposal stage, a re-evaluation is performed by SMEs or responsible groups to identify changes that may have been introduced from the proposal to the official publication. Any changes from proposal to official are taken into account to adjust the implementation plan that was developed at the proposal stage; changes from proposal to official are also documented in the change control process to properly implement the official revision. The work then progresses to execution of the implementation plan, thereby providing compliance with the updated official pharmacopoeial requirements. If the pharmacopoeia revision was not previously evaluated when it was proposed, this is the first time a company will identify the update, and all the steps of the impact assessment detailed earlier in the process must be accomplished in the six-month timeframe typically allowed between publication of the new edition or supplement and the official date. The evaluation must now focus on what has changed from the previous official requirements, including how these are reflected in the company's documentation, to the newly updated official requirements. Failure to accomplish all this activity on time, including any laboratory evaluation or data-mining, culminating in the completion of change control, results in a potential compliance gap for the company, which may be revealed upon inspection by regulatory agencies. A change control process is challenging at best but is a critical part of the compendial process to ensure compliance with current pharmacopoeia requirements. The change control process ensures input from impacted stakeholders, including the quality and regulatory groups, which is especially important when the change will impact multiple sites, multiple products, and potentially hundreds of product registrations around the world. The timing necessary to submit registration updates and receive any needed approvals from the health authorities, potentially over a time horizon of many years, must be considered and managed properly during this interim period. Although the functional organization and details of the overall surveillance process may vary from one company to the next, there are common elements among the approaches that are effective: having multiple SMEs assist in the assessment; starting at the proposal stage; providing responses to the pharmacopoeia; and planning for implementation of updated requirements. Even in the best compendial affairs programs, there are occasions when a company may have difficulty complying with some of the specific, updated official pharmacopoeial requirements. To address this situation, the last step of the industry process, when needed, is for a company to submit a request for revision to the pharmacopoeia authority, advocating for further revision of the general chapter or monograph that was just made official. This request may not be received favorably by the pharmacopoeia if the company did not provide any comments when the revision was first proposed. Similar considerations as those for developing a company's response to a proposal also inform the development of a request for revision to an official update, complete with scientific rationale and data needed to support the requested change. This input from a company starts the entire pharmacopoeia revision process from the top, which again triggers the industry surveillance process. As noted before, pharmacopoeias continually evolve and given all the different viewpoints of the impacted stakeholders in a company, one can begin to get an appreciation of the challenges and complexity faced by all. References 1. J. M. Wiggins and J.A. Albanese, "Why Pharmacopoeia Compliance Is Difficult," BioPharm International Regulatory Sourcebook eBook, 26–34 (September 2019). the focus of their discussion is on changes that have broader impact to the entire industry, as seen with general chapters, which are used by many companies. Key benefits of engaging with industry groups include recognizing you are not in this alone; that it is helpful having many eyes look at the information; and there is power in numbers. Par ticipating in these g roups as par t of the compendial pro - cess increases a company's abil- Contin. from page 29 Regulatory Sourcebook Pharmacopoeia Compliance Series Bio/pharmaceutical industry surveillance of compendial changes: Process in detail (cont.)