Comparison of Combination Product Regulations: Challenges and approval pathway in the US and Europe

Abstract

A complex regulatory issue related to the combination products, which combine drugs, device, or biologics, is found in the United States (US) and the European Union (EU). In this review, this paper compares their unique regulatory systems that involve, among other things, classification and approval channels. The Office of Combination Products (OCP) at the FDA regulates in the US based on Primary Mode of Action (PMOA), whereas in the EU, there is not a single definition but on the Medical Device Regulation (MDR), Medicinal Products Directive, frequently a Notified Body Opinion (NBOp) is required, under MDR Article 117. Though their products present greater therapeutic efficacy and patient adherence, there are obstacles such as PMOA determination, intercenter cross-coordination, and Notified Body capacity which present challenges to the products. Subsequent regulatory development should aim at harmonization, integration of digital health, real-world evidence and possible EU centralization as a way to simplify development and make it safe.