OBJECTIVES : Combination products (CPs), combining two or more drug, device and/or biologic, have the potentials to enhance therapeutic advantages. While CPs are becoming increasingly complex, the challenges faced by the drug regulatory authorities (DRAs) in ensuring their quality, safety and effectiveness are immense. To better address the regulatory issues, DRAs have developed and adopted regulatory science (RS). However, little is known about how RS is driving the advancement in CPs regulation. This research aimed to analyze the experiences of RS development in CPs based on a cross-country comparison.

METHODS : DRAs in China (National Medical Products Administration, NMPA), the United States (Food and Drug Administration, FDA) and the European Union (European Medicines Agency, EMA) were the study targets as they had officially launched initiatives in RS. Documentary analysis of government documents were conducted for data collection.

RESULTS : DRAs have seen a steady increase in CP applications in recent years. The definition, classification and regulatory requirements of CP are different across DRAs. Product classification and the corresponding review process are determined based on the primary mode of action at the discretion of the assigned department in charged of drug, medical device or biologics. With the adoption of RS, FDA mainly focused on post-marketing adverse-event reporting, good manufacturing practices and developing adaptive equivalence standards; EMA created an integrated evaluation pathway for product assessment and developed network-led partnerships with academia to facilitate integration of science and technology in product development and evaluation; NMPA clearly indicated CP was among the one of the 9 prioirty of actions and had developed a guidance on CP classification and a database of CP regulatory requirements and decision-making algorithm.

CONCLUSIONS : Consideing the globalization of pharmaceutical products nowadays, RS should be adopted by DRAs in a collaborative manner to help achieve standardization of regulatory requirements.