Issue link: http://www.e-digitaleditions.com/i/1222740
Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 31 using both methods until all approvals are received, with ob- vious impact on the laboratory. Another option is to continue to use the currently approved methods until a fixed imple- mentation date or until approvals are received in key markets, then switching over to the monograph methods, while still waiting for approval in the remaining markets. This approach carries some risk in ensuring compliance with both methods, but relieves the laboratory from having to perform duplicate testing in the interim. The compliance risk can be mitigated by the documented equivalency between the two methods, mentioned earlier. Another compliance risk can emerge if the regulators in one country reject the updated registration, forcing the company to continue duplicate testing to ensure global compliance and release of the product to all countries. Given the range and nuance of compliance challenges associated with the "replace" option, it is clearly import- ant that all impacted stakeholders across the company, in- cluding analytical, quality, and regulatory, work together to develop and align on the strategy and then execute the implementation plan for adopting the monograph, while ensuring compliance with product registrations. As noted previously, despite the challenges, one benefit of the "replace" option is that the company can remove many of the details of the analytical methods from the registration to refer in- stead to compliance with the monograph. This simplifies the information detailed in the registration and enables the company to more easily implement subsequent revisions to the monograph, which ensures ongoing compliance with "current pharmacopoeia requirements", as expected by reg- ulatory agencies around the world (3). Keep. The other option, with a significantly different method in the monograph compared to the approved reg- istration, is to "keep" the currently approved method in- stead of switching to the monograph method. There may be a strong preference for a company to continue using an analytical procedure that has been used for many years to ensure the quality and stability of the drug substance and product. Again, the equivalency of the approved method and the monograph method must be demonstrated. The General Notices in most pharmacopoeias allow the use of alternative methods that are equivalent or better than those in the monograph. Because of this, for most countries, there would be no need to update the product registration if the decision has been made to keep using the currently approved method instead of the monograph method. The demonstration of equivalency would be shown upon facility inspection, if requested, as evidence of compliance with the monograph requirements. However, if the new or significantly different method is listed specifically in a monograph of the Ph. Eur., then submission of a variation is required in European coun- tries that are members of the EMA or signatories to the Ph. Eur. convention. The reason for this is the specific lan- Throughout this series of articles, it has been emphasized that the bio/pharmaceutical industry must comply with requirements published by pharmacopoeias around the world. Several considerations have been presented to illustrate that pharmacopoeia compliance can be difficult. A previous article highlighted compliance challenges resulting from the elaboration of monographs for drug substances and products. These challenges can be considered ex ternally-based, driven by decisions made by the pharmacopoeias during the monograph development process. There are other compliance challenges that are internally-based, resulting from decisions made by one functional area in the company without consideration of the broader impact to other functional areas throughout the organization. One such example can be found with raw materials and excipients, where a consistent, cross- functional approach is needed to ensure the appropriate selection, sourcing, testing, and filing of the materials used to manufacture bio/pharmaceutical products in a global environment, ensuring compliance with applicable compendial and regulatory requirements. This case study is based on the experience of one of the authors but is applicable to all companies across the broader industry, illustrating the potentially surprising point that some compliance difficulties may be of the company's own making. Click here to read the full case study at PharmTech.com. A Case Study in Pharmacopoeia Compliance: Excipients and Raw Materials The General Notices in most pharmacopoeias allow the use of alternative methods that are equivalent or better than those in the monograph.