The diversity in regenerative medicines regulations in Europe, USA and Japan
Cell & Gene Therapy Insights 2019; 5(8), 1031–1042.
Substantial efforts have been made to increase harmonization across regulatory authorities for the regulation of regenerative medicines (RMs), yet variations still exist in market authorization (MA) processes with regards to terminology, product classification, and evidence requirements. Regulatory and MA processes were examined in the EU, the USA and Japan. RMs are evaluated under similar regulatory frameworks as either traditional medicines or biologicals by the Food and Drug Administration in the USA, with a risk-based approach acknowledging the RM’s specificities. In the EU, RMs are regulated under the centralized procedure by European Medicines Agency (EMA), with an additional step that a draft opinion is prepared by Committee for Advanced Therapies (CAT) prior to a final MA opinion from Committee for Medicinal Products for Human Use (CHMP). The Pharmaceuticals and Medical Devices Agency (PMDA) in Japan has shifted the regulatory paradigm of RMs with a time-limited, conditional MA pathway to accelerate patient access and increase global competitiveness. Opponents argue that such a system may be too permissive in potentially exposing vulnerable patients to treatments with questionable efficacy and safety. The FDA and EMA have shown more willingness to accept real world evidence (RWE) to support MA applications. RWE was more commonly used in post-market surveillance by the PMDA in the past, but efforts are underway to explore the possibility of using patient registry data for MA application. To avoid the use of unauthorized RMs, the FDA has temporarily established the Tissue Reference Group (TRG) Rapid Inquiry Program (TRIP) to support sponsors in the regulation of specific RMs, along with the release of final guidelines to explain the principle of ‘minimal manipulation and homologous use’. The PMDA requires a specific expert committee review for RMs (including autologous RMs for homologous use) administered in medical practices and research based on effects on human health. The ‘hospital exemption’ rule in the EMA still needs more clarification to ensure its harmonious implementation across different Member States. Expedited approval programs in three jurisdictions showed disparities in eligibility criteria, application timelines and incentives provided to sponsors.