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18 Pharmaceutical Technology ® Regulating Innovation, Quality, and Risk eBook January 2024 PharmTech.com Regul ations Regul ations lieu of conducting an FDA site inspection. The 2012 Food and Drug Administration Safety and Innovation Act gave FDA the authority to enter into these agreements if FDA determines that a foreign authority is capable of conducting inspections that meet US requirements. Under MRAs, FDA now collaborates with European in- spectorates, including those of the United Kingdom and Switzerland, to avoid conducting duplicate inspections and focus resources on inspecting drug manufacturing facilities with higher US public health risks. The power of MRAs was on full display at the height of the global COVID-19 public health emergency; critical data from MRA partner inspections enabled facility assessments and product approvals despite the travel restrictions imposed by various governments. FDA is also part of the International Coalition of Medicines Regulatory Authorities (ICMRA), a group of 39 regulatory authorities that provides strategic direction to jointly address common challenges, such as those posed by the COVID-19 pandemic. ICMRA is working to establish a new capability for Pharmaceu- tical Quality Knowledge Management that ensures participating regulators have timely and complete information related to an applicant's qualit y and risk management. ICMRA's knowledge management strategy could enable the simultaneous submission of harmonized pharmaceutical manufacturing infor- mation from sponsors and the simultaneous access to that information by multiple regulators. International convergence of this scope requires the collaboration of many, and ICMRA is calling on the international com- munity of regulators, legislators, and manufacturers to advance this strategy for the benefit of patients. International regulatory divergence can not only keep manufacturers from pursuing new treatments and technologies, but it can also complicate executing a manufacturing change after FDA approves a drug. One manufacturing facility may supply drug product to many different countries, and it can be difficult to move a manufacturing process to a new facility unless all of those countries agree to it. Consider the impact of COVID-19 on supply chains and the need for manufac- turing agility. Many manufacturers needed to quickly move or modify their manufacturing processes to re- spond to challenges posed by COVID-19. In the years prior to 2020, FDA would assess around 7000 applica- tion supplements for human drugs. In 2020 alone, FDA approved more than 10,000 application supplements for quality-related changes for human drugs. To improve international manufacturing agility, FDA is part of two ongoing pilot programs with ICMRA on collaborative international assessments of postapproval changes and collaborative hybrid inspections to inform assessments. The objective of the pilot program on po- stapproval changes is for multiple regulatory authorities to engage in a single interactive, collaborative assess- ment of proposed postapproval changes. The collabora- tive hybrid inspection pilot of a manufacturing facility will use a combination of on-site inspection and remote assessment for regulators to collaboratively assess a fa- cility. This pilot will provide information on how to pre- pare, execute, and report the inspection and how stake- holders can engage surrounding the inspection. Ideally, the pilots will identify potential areas for alignment or harmonization across participating regulatory regions in the context of manufacturing lifecycle management and find potential conditions (e.g., products/cases) for future collaborative assessments. To be clear, the world is still very far from a single reg- ulatory position on quality, and barriers undoubtedly exist between the unoptimized present and the desired future. Yet, the technical barriers may be less signifi- cant than the 'people' barriers. Consider that technol- ogy advancements enable many organizations to use international cloud-based data systems to collaborate globally. The hardest challenge may well be the 'people' challenge: getting people from different countries with different regulations to agree to change the way they do things. Current international efforts suggest that this change may have begun. References 1. Cox, B. Woodcock: The US FDA Sets the Stage for Global Quality Dossiers. Pink Sheet. Jan. 10, 2020. 2. Fisher, Adam C., et al. An Audit of Pharmaceutical Continuous Manufacturing Regulatory Submissions and Outcomes in the US. International Journal of Phar- maceutics 2022 622: 121778. 3. ICH. M4: The Common Technical Document. www. ich.org/page/ctd (accessed Jan. 20, 2023). 4. Beierle, J.; Cauchon, N.S.; Graul, T., et al. Toward a Sin- gle Global Control Strategy: Industry Study. Pharma- ceutical Engineering January/February 2022. ■ Ed itor 's Note: T h i s a r t ic le w a s pre v iou sly publ i shed i n Pharmaceutical Technology's February 2023 issue. A regulatory future could include harmonized regulatory expectations for data elements and standards.