Table 4 Examples of quality and safety requirements of allogeneic platelet lysates and platelet extracellular vesicles (EVs; p-EVs) as medicinal preparations
Platelet lysates | Platelet extracellular vesicles | |
|---|---|---|
Blood donors | Meet health requirements for donations of whole blood or platelet concentrates (PCs) | Meet health requirements for donations of whole blood or PCs |
Whole blood or platelet concentrate donations | Meet overall quality and safety requirements for clinical use: testing of viral markers, blood cell counts within specifications | Meet overall quality and safety requirements clinical use: testing of viral markers, blood cell counts within specifications |
Pathogen-reduction treatment of individual donations | Licensed pathogen-reduction treatment of PCs (e.g., photochemical treatment) | Pathogen-reduction treatment of PCs (e.g., photochemical treatment) demonstrated to not affect EV functional activities |
Treatment of PCs | Freezing, thawing, and pooling | Freezing, thawing, and pooling |
Optional processing steps | Fibrinogen conversion (e.g., CaCl2 activation); dedicated virus-reduction treatment (e.g., gamma-irradiation; electron-beam; solvent-detergent), low-speed centrifugation; depth filtration; bacterial filtration; aseptic filling; freezing | EV generation from PCs (freeze–thaw, sonication, CaCl2 activation); low-speed centrifugation; ultracentrifugation; size exclusion chromatography; bacterial filtration; aseptic filling; freezing |
Quality control | Meet specifications: protein content; microbial sterility, endotoxins; pH; osmolality; representative growth factor content (e.g., PDGF-AB); functional assay (e.g., cell proliferation test) | Meet specifications: protein content; EV number; representative p-EV markers; microbial sterility; endotoxins; pH; osmolality; representative growth factor content (e.g., PDGF-AB); functional assay (e.g., cell proliferation test; internalization assay) |