Worldwide Regulatory Reliance: Results of an Executed Chemistry, Manufacturing and Control Post Approval Change Pilot

Abstract

Post-approval changes (PACs) are integral to pharmaceutical product lifecycle management ensuring that the product remains safe, effective, and compliant with evolving standards. However, managing these changes across multiple regulatory jurisdictions remains a challenging endeavor due to diverse regulatory requirements and timelines across national regulatory authorities (NRAs). This results in delays obtaining approval from NRAs, impacting global supply chains, and ultimately jeopardizing timely access of essential medical products to patients. In 2021, the WHO issued the Good Reliance Practices (GReIP) guidance to encourage streamlined PAC review and approval process while maintaining access to quality-assured, safe, and effective medicinal products. NRAs are encouraged to rely on the assessment completed by a reference authority that agrees to provide the outcomes of its regulatory expertise. The ultimate objective of this guidance is to accelerate the overall process for PACs, ultimately fostering more equitable and timely access of medical products to populations who need them. This approach was tested in a CMC PAC pilot to determine the feasibility of using the principles of regulatory reliance based on the recommendations outlined in the GReIP with the goal of establishing a predictable, 6-month approval timeframe across multiple NRAs. The design and management of this pilot is described in Gastineau et al.

This paper describes the outcomes of the pilot which demonstrates that regulatory reliance is feasible. Of the 21 Regulatory NRAs that agreed to participate, 55% were able to complete the review within 6 months; within 10 months, 95% of approvals were received and, after 16 months, all participating countries had approved the PAC. The use of a Q&A SharePoint Tool allowed for visibility of the questions raised and company responses amongst NRAs. Feedback on this reliance pilot was solicited from the participating NRAs and provides further support for future CMC PAC reliance cases.