Model Risk Assessment for Viral Safety on the Potential Sources of Risk Element on the Manufacturing of Drug Substance. O: Occurrence; D/C: Detection and Control Strategy; S: Severity
| Raw Material | Expression/Production System | Upstream Process System | Downstream Purification Process | Q5a-compliance of the Process | O | D/C | S | RPN |
|---|---|---|---|---|---|---|---|---|
| Animal- or human-derived raw materials of un-documented source or incomplete viral testing | Human and non-human Primates | Live animals (Genetically engineered animals, Ascites) | Downstream process does not have multiple orthogonal robust virus reduction steps | Q5a-non-compliant | 6 | 2,4,6 | 10 | 120,240,360 Medium to High |
| Animal- or human-derived raw materials with well-documented source and viral testing | Other Mammalian Cells: Murine, CHO | Non-bioreactor System (e.g., Roller Bottles) | Downstream process includes a virus filter and one additional robust virus reduction step | Q5a-compliant with some minor deficiency | 4 | 2,4,6 | 10 | 80,160,240 Low to High |
| No animal- or human-derived raw materials used | Insect Cells/Plants/Yeast/Bacteria | Bioreactors | Downstream process contains multiple orthogonal robust virus reduction steps including a virus filter | Q5a-compliant (Cell line Qualification, Unprocessed Bulk Testing, and Viral Clearance studies) | 2 | 2,4,6 | 10 | 40,80,120 Low to Medium |