Risk Analysis with Cell Therapy Products Related to Input Materials—Cell Transformation and Expansion
| Input Materials | Risk Identification | Risk Rating | Risk Mitigation/Critical Process Controls |
|---|---|---|---|
| Single-use consumables | Open (e.g., transfer bags, roller bags, cassettes, etc.) | High | Sterile, disposable consumables |
| Closed | Low | ||
| Cell banks | Contamination | Moderate | Sterility, mycoplasma and infectious agent screening |
| Transduction | Viral and bacterial vectors | Low to Moderate | Infectious agent screening; Sterile filling/sterility testing |
| Cell expansion | Multiple aseptic manipulations | Low to Moderate | BSC, RABS and isolator systems; Bioburden Monitoring |
| Culture media | Fetal bovine serum and other components | Low to Moderate | Source certification; Adventitious agent screening; Terminal sterilization (pasteurization, chemical treatment or irradiation) |
| Microcarrier | Immunomagnetic beads | Low | Terminal sterilization |
| Utilities | Pharmaceutical-grade water | Moderate | GMP and compendial compliance; Microbial monitoring, Endotoxin monitoring |
| Compressed gases | Moderate | Sterile filtration at Point of use | |
| Facility | Containment | Low to Moderate | BSC, isolators, RABS, etc. |
| Segregation of process steps | Labelling, consideration for dedicated work areas for high-risk contamination steps, appropriate disinfection between steps, process flows, and HVAC cascades | ||
| Personnel and materials flow | Clearly defined and physically separate or procedurally segregated entry and exit. Transfer disinfection procedures for materials, adequate protection of sterile materials for transfer | ||
| Cell harvesting | Digestive enzymes (e.g., trypsin, collagenase, DNase/RNase, restriction endonucleases), growth factors, cytokines, and monoclonal antibodies | Low to Moderate | Terminal sterilization; Use of non-animal-derived materials |
| Cell storage solution | Buffers; saline; surfactants; cryo-protectants | Low | Sterile filtration |