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www.biopharminternational.com March 2020 BioPharm International eBook 17 standards contained in the mono- graph should closely align with the requirements in the approved drug product registrations. The result- ing standards in the monograph for a drug substance can be used for multiple product formulations and dual-active products. Proactive engagement in the monograph development process helps build a strong collaborative relationship with the pharmaco- poeia authorities and enables those involved in compendial activities in a company to become acquainted with individual scientists at the pharmacopoeias. This involvement can be beneficial in other com- pendial activities for the company, including greater effectiveness with responses submitted to other pro- posed revisions published by the pharmacopoeias. A not her potent ia l benef it of proactive participation is the pos- sibility of establishing a harmo- nized monograph across multiple pharmacopoeias (see Sidebar, page 22). Proactive participation, how- ever, comes with a higher upfront resource cost to prepare the mono- graph submission and respond to questions during its elaboration. Additionally, the outcome of the monog raph is not g ua ra nteed, so there could be impact to the company's product registrations and quality testing despite collab- oration with the pharmacopoeia authorities. One important benefit of a pro- active approach for an innova- tor 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 qual- ity standards in their approved drug product registration, rather than having to comply with monograph requirements developed by another company. Additionally, physical reference standard materials sup- plied by the innovator company to support the monograph provide similar benefits and potentially simplify the processes for the com- pany, eliminating the need to per- form comparison testing with an in-house standard. Reactive approach On the other hand, the case against active participation in monograph development is that fewer resources are needed upfront during the elab- oration process. No work is required to pull together the information needed for submission of the mono- g raph. D u r i ng t he t i me when there is no monograph, each com- pany having regulatory approval must comply with its own active registrations, meaning no work is needed to demonstrate equivalence or implement new methodologies from the monograph. A company can still comment when the pro- posal of the monograph is first pub- lished, providing specific feedback on items of concern. This approach, which is more reactive, requires higher resource commitment once the draft monograph is published, with rapid evaluation needed for any new methods it may contain. It can be difficult for a company to significantly influence the draft publication given the work already invested by the pharmacopoeial scientists. Once published as an official monograph, this reactive approach potentially makes com- pliance more difficult for the com- pany. In the authors' experience, there is a benefit in proactive partic- ipation in the monograph devel- opment process. However, neither approach is right or wrong; it sim- ply comes down to a company's decision. The consequences can best be summed up as "pay me now or pay me later". Either approach, whether proactive participation or a reactive position, will require periods of resource-intensive effort. Either approach can have an impact on the outcome of the final mono- graph, determining how much lab- oratory work or how many filing updates may be needed to remain compliant. It is useful for a company to determine its "typical" approach to monograph development, while understanding that it is not a one- size-fits-all outcome. There are scenarios where it may not be advis- able for a company to participate in monograph development for a particular product, depending 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 bet- ter treatments in development, then a company may choose not to work on monograph elaboration for that material. 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 elabo- ration process. Ultimately, it is important for a company to decide whether and how they will participate in mono- graph development. This choice will shape how the compendial af fairs f unc tion is staf fed and empowered for the company. The compendial affairs function should communicate the risks and benefits of a proactive or reactive approach to monog raph 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 monog raph elaboration is Regulatory Sourcebook Pharmacopoeia Compliance Series