Mesenchymal stem cell-derived extracellular vesicles as next generation drug delivery platforms

Table 5 Regulatory and quality characteristics required for clinical translation of mesenchymal stem cell-derived extracellular vesicles pharmaceutical products

Quality characteristics	Regulatory expectation	Analytical method	Clinical relevance	Ref.
Identity	EV marker confirmation	CD63/CD81, WB, ELISA	Ensures correct product characterization and prevents misidentification of EV preparations	[21]
Potency	Mechanism-linked assay	Angiogenesis, T-cell suppression	Demonstrates therapeutic efficacy and supports dose selection	[180]
Purity	Removal of proteins/DNA	SEC, TFF, PicoGreen	Prevents contamination-related toxicity and improves product safety	[181]
Sterility	GMP requirement	USP <71>: Sterility tests	Required to ensure patient safety during systemic administration	[192]
Stability	Shelf-life	Freeze-thaw, lyophilization	Enables long-term storage and consistent therapeutic dosing	[182]
Process comparability	Manufacturing consistency	CMC validation	Required when manufacturing changes occur during scale-up or optimization	[193]
GMP manufacturing	Quality assurance	Process validation	Ensures consistent large-scale production suitable for clinical trials	[194,195]

EV: Extracellular vesicle; WB: Western blotting; ELISA: Enzyme-linked immunosorbent assay; SEC: Size-exclusion chromatography; TFF: Tangential flow filtration; GMP: Good manufacturing practice; USP: United States Pharmacopeia; CMC: Chemistry, manufacturing and controls.