Unleashing the Power of Reliance for Post-Approval Changes: A Journey with 48 National Regulatory Authorities

• Published in: Therapeutic innovation & regulatory science 2024-11, Vol.58 (6), p.997-1005
• Main Authors: Mangia, Francesca, Lin, Yameng (Melly), Armando, John, Dominguez, Kareny, Rozhnova, Vera, Ausborn, Susanne
• Format: Article
• Language: English
• Subjects: Analysis; Antibodies, Monoclonal - therapeutic use; Drug Approval - legislation & jurisprudence; Drug Approval - organization & administration; Drug Safety and Pharmacovigilance; European Union; Global health; Humans; Manufacturing; Manufacturing industry; Medicine; Monoclonal antibodies; Pharmacotherapy; Pharmacy; Pilot Projects; Product life cycle; Product Surveillance, Postmarketing; Public health; Regulatory agencies; Variation; World Health Organization
• ISSN: 2168-4790; 2168-4804; 2168-4804
• DOI: 10.1007/s43441-024-00677-8

Post-approval changes (PACs) to marketed products are routinely introduced to continuously enhance the product lifecycle management. However, bringing a chemistry, manufacturing and control (CMC) change through the global health authorities can be a complex and lengthy process taking up to several years, therefore negatively impacting supply continuity. In order to accelerate the review and approval of regulatory submissions and ensure continuous supply to patients, the World Health Organization (WHO) is strongly supporting the implementation of reliance among National Regulatory Authorities (NRAs). While some promising developments have been made with the use of reliance pathways for initial marketing authorizations, reliance is still not widely used for PACs. With the support of the European Medicines Agency (EMA) and WHO, Roche launched a reliance pilot based on EMA approval to file a supply critical variation for a monoclonal antibody. The variation constitutes major changes to the approved manufacturing process. Sameness of the product is ensured by submitting to all participants the same variation package as in the EU. The objectives of the pilot are to ensure continuous supply of this critical medicine by targeting global approval in 6.5 months, to promote regulatory convergence by waiving country specific requirements, and enhance greater transparency by sharing EMA Committee for Medicinal Products for Human Use (CHMP) final assessment report and Q&As to participating NRAs. Globally 48 NRAs have agreed to join the pilot. This article outlines the process of establishing the pilot project, including a planning phase and an engagement phase with the EMA, WHO and the participating NRAs.