From laboratory to clinic: Bridging regulatory and manufacturing gaps in stem cell-based therapies

Table 1 Representative regulatory frameworks for cell and gene therapies (non-exhaustive)

Jurisdiction	Key guidelines/regulations	Remarks
United States (FDA)	RMAT designation (21st Century Cures Act, 2016)[18]; multiple cell and gene therapy guidance documents (e.g., potency testing, viral safety)	Offers expedited development pathways; regulated under biologics framework
EU (EMA)	ATMP GMP guidelines (EudraLex Vol 4 Part IV, 2017)[17]; ATMP Regulation EC 1394/2007	Dedicated GMP annex for ATMPs; emphasizes risk-based quality management
Japan (PMDA)	Regenerative Medicine Act (2014); PMDA technical guidance on cell therapies	Conditional and time-limited approvals; includes nonclinical safety assessments, such as iPSC tumorigenicity[23]
China (NMPA)	Trial guidelines for stem cell products (2015-2023); GMP management updates (2022)[11,19]	Developing regulatory framework with a parallel “drug-like” pathway
WHO	TRS 1048 Annex 3 (2023); previous TRS 878 (1998) tumorigenicity recommendations	Defines ATMP categories and promotes regulatory harmonization[13,15]
PIC/S	GMP Annex 2A for ATMPs (effective May 2021)[12]	Supports global harmonization of GMP requirements, aligned with EU standards
ICH	Q5A(R2) Viral Safety (November 2023)[28]; additional quality modules	Emphasizes viral safety and risk-based management for biotech products

FDA: Food and Drug Administration; RMAT: Regenerative medicine advanced therapy; ATMPs: Advanced therapy medicinal products; EU: European Union; EMA: European Medicines Agency; GMP: Good manufacturing practice; PMDA: Pharmaceuticals and Medical Devices Agency; iPSC: Induced pluripotent stem cell; NMPA: National Medical Products Administration; WHO: World Health Organization; PIC/S: Pharmaceutical Inspection Co-operation Scheme; ICH: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use.