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Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 17 volvement can be beneficial in other compendial activities for the company, including greater effectiveness with re- sponses submitted to other proposed revisions published by the pharmacopoeias. Another potential benefit of proactive participation is the possibility of establishing a harmonized monograph across multiple pharmacopoeias (see Sidebar). Proactive participa- tion, however, comes with a higher upfront resource cost to prepare the monograph submission and respond to ques- tions during its elaboration. Additionally, the outcome of the monograph is not guaranteed, so there could be impact to the company's product registrations and quality testing despite collaboration with the pharmacopoeia authorities. One important benefit of a proactive approach for an innovator company is avoidance of the development of a monograph by a competitor, which can create compliance challenges. There are benefits to an innovator company having the public standard in the pharmacopoeia based on the quality standards in their approved drug product reg- istration, rather than having to comply with monograph requirements developed by another company. Additionally, physical reference standard materials supplied by the inno- vator company to support the monograph provide similar benefits and potentially simplify the processes for the com- pany, eliminating the need to perform comparison testing with an in-house standard. Reactive approach. On the other hand, the case against ac- tive participation in monograph development is that fewer resources are needed upfront during the elaboration process. No work is required to pull together the information needed for submission of the monograph. During the time when there is no monograph, each company having regulatory ap- proval must comply with its own active registrations, mean- ing no work is needed to demonstrate equivalence or imple- ment new methodologies from the monograph. A company can still comment when the proposal of the monograph is first published, providing specific feedback on items of con- cern. This approach, which is more reactive, requires higher resource commitment once the draft monograph is pub- lished, with rapid evaluation needed for any new methods it may contain. It can be difficult for a company to signifi- cantly influence the draft publication given the work already invested by the pharmacopoeial scientists. Once published as an official monograph, this reactive approach potentially makes compliance more difficult for the company. In the authors' experience, there is a benefit in proactive participation in the monograph development process. How- ever, neither approach is right or wrong; it simply comes down to a company's decision. The consequences can best be summed up as "pay me now or pay me later". Either ap- proach, whether proactive participation or a reactive posi- tion, will require periods of resource-intensive effort. Either approach can have an impact on the outcome of the final monograph, determining how much laboratory work or how many filing updates may be needed to remain compliant. It is useful for a company to determine its "typical" ap- proach to monograph development, while understanding that it is not a one-size-fits-all outcome. There are scenarios where it may not be advisable for a company to participate in monograph development for a particular product, de- pending on scientific, regulatory, or business drivers. For example, if a product is expected to have a short lifetime in the market with limited utility to patients because there are better treatments in development, then a company may choose not to work on monograph elaboration for that ma- terial. Additionally, for older compounds (more than 25–30 years), if a monograph does not already exist, the benefit of creating one may not justify the resource cost needed to complete the elaboration process. Ultimately, it is important for a company to decide whether and how they will participate in monograph development. This choice will shape how the compendial affairs function is staffed and empowered for the company. The compendial affairs function should communicate the risks and benefits of a proactive or reactive approach to monograph development to management and critical internal stakeholders. It is common to have to educate the product support team—product director, regulatory support, quality—as to the reasons why monograph elaboration is needed. It is a daunting task to get approval for each new monograph submission, with the scientific data re- quired to support the elaboration activities. It is best to embed the monograph strategy into established compendial processes, so it becomes a "routine" activity that requires limited internal approvals to proceed. Consideration of appropriate timing for monograph submission The GPhP guidance states that pharmacopoeial standards should be available for drug products and their active ingre- dients at an appropriate time to support and benefit patients through the availability of medicines with consistent quality (8). The critical question within this statement is what is an "appropriate time". If a company decides to participate in the development of a new monograph, they must ask when they will start the process. The appropriate timing will typically vary for each company, for each situation, or even for each product in a company's portfolio. As with the prior question of whether a company should participate in monograph development, ex- ploring the subsequent question of when to participate reveals there is not necessarily a consistent, single answer. Focusing on the question of timing, two perspectives should be considered: that of the pharmacopoeia and that of the industry. Pharmacopoeia timing. The process to develop a new mono- graph in the pharmacopoeia typically takes two to three years. Figure 1 shows the preferred timing for new monograph de- velopment from the viewpoint of various pharmacopoeias, reflecting several considerations. Typically, the Ph. Eur. and USP monographs are the earliest to be elaborated, with the preferred Ph. Eur. timing stated as five years post-approval to take advantage of its P4 procedure (12), in which the necessary