Issue link: https://www.e-digitaleditions.com/i/1192284
Pharmaceutical Technology REGULATORY SOURCEBOOK DECEMBER 2019 33 units, a common response is, "it's not my job," among others that were touched upon in the second article of this series (1). Given the span of control where SMEs reside across the company, the understanding, commitment, and support by executive leadership and functional area management across the company is important in ensuring routine SME participation in this surveillance process to ensure compliance. The ongoing effort to keep all stakeholders involved and up to date with ever- changing pharmacopoeial requirements is quite a task and should not be underestimated in resource planning for the compendial affairs group. Proposed changes: Evaluate, develop a response, and plan for implementation. Typically, for global pharmacopoeias as well as many of the national pharmacopoeias, new and revised requirements are first published as proposals, with an opportunity for public review and comment prior to becoming of f icial. At the pharmacopoeia proposal stage in the industry surveillance process, two important actions are undertaken, usually in parallel, for items with potential impact to the company: develop a response to the proposal and plan for implementation of the changes ( Figure 1). Submitting comments to pharmacopoeia proposals requires a company decision to pursue this proactive approach to the overall process. There are clear benefits in doing so, but the trade-off is the resources needed by the company to perform this work. Not every revision proposed by the pharmacopoeia requires a response; indeed, the vast majority do not. The assessment step in the surveillance process helps to identify the changes where a response may be beneficial. For these proposed changes, developing appropriate comments can require significant time and effort. This is particularly true, for example, when laboratory work is needed to evaluate a proposed change to an analytical method, or when data-mining of release and stability information is required to determine whether a company can comply with a proposed tightening of an impurity limit. For the first action, when a response is needed, the compendial affairs function works with SMEs and impacted stakeholders to evaluate the change and prepare scientifically-based comments to submit to the pharmacopoeia authority. In most companies, the compendial af fairs function is responsible for this advocacy, aimed at influencing decisions about the official content that will be published in the pharmacopoeias. The compendial affairs advocacy may be associated with a company's larger regulatory intelligence activities. Ef fective advocacy requires the compendial affairs function to clearly define what is needed from the SME assessment of a change and in what manner the information is provided back to the compendial af fairs group (e.g., comments, suggestions, data). The compendial affairs function must let the SME know when the assessment is due, typically at least 14 days before the response is due to the pharmacopoeia. This allows the compendial affairs function to work through and follow up on internal comments received. It is important that SMEs understand that sound scientific rationale and data (where appropriate) are required to support a request for change to a proposed general chapter or monograph. It is not enough for a scientist to disagree with a statement or requirement without offering the reason for the objection, a suggestion for a change in the statement or requirement, and the appropriate rationale for the suggestion. To enable effective and appropriate commenting, it is recommended that the compendial affairs function develop a training program to help their SMEs in this work. Without this training, the compendial affairs group may spend significant time rewriting or interpreting the comments from SMEs prior to sending them to the pharmacopoeia authority. One possible outcome of the rewrite is that the original intent of the SME comments could be lost. Af ter these internal comments have been received, potentially from multiple stakeholders, the compendial affairs function then shapes the information into a consistent, coherent, and hopefully compelling response that is provided to the pharmacopoeia agency before the established comment deadline. For commenting to the national pharmacopoeias, the connection to a company's local contact group is essential so comments can be translated into the local language prior to submission. For countries such as China, where turn- around times for review and commenting can be short, this process and expected roles must be well-defined ahead of time to maximize the chances for the company to be successful in their advocac y. At this stage in the surveillance process, a company has usually filtered and determined which proposed changes may have the greatest potential impact. These major changes often benefit from the effort required by a company to develop and submit comments in response to the proposal. For the remaining items identified with potential impact, an assessment serves to look further into the details of the change to determine whether there is minor impact or no impact to the company. It may be surprising, but true, that this deep dive into details is needed to make this final determination of impact. As illustrated in Figure 2, the remaining 400 items each year are assessed and filtered to find about 100 with minor Bio/pharmaceutical industry surveillance of compendial changes: Process in detail (cont.) Proposal Published New Edition/ Supplement Published Comment Deadline Pharmacopoeia Activity Official Date 0 3 Total Time (months) 12 18 12 months to plan for implementation 6 months to implement Figure 3. Typical timeline for pharmacopoeia revisions to move from proposal to official.