Factors to Be Considered in Particle Risk Assessment
| Parameter | Potential Risk Factor |
|---|---|
| Patient factors | Age, gender, weight, disease being treated, underlying illness, immune status, other treatments, physical activity |
| Route of administration and use of filtration at point of administration | Subcutaneous, intramuscular, intravenous, high-volume infusions, intrathecal, intraarticular, intraocular, intraarteriol, other; use of filter (and type) at point of use |
| Volume of administration | Number of particles likely present per volume of administration |
| Size | If visible particles are present, determine the likelihood of additional subvisible particles present and the likely size. Determine if the subvisible particles are within acceptable limits |
| Fate in body | Remains at site of administration (e.g., subcutaneous or closed cavity), peripheral versus central venous administration, intrinsic reactivity (immunogenicity, pro-inflammatory, nonreactive/inert) |
| Particle type | Inherent: intact therapeutic protein, denatured therapeutic protein, degree of degradation, other protein component(s) Intrinsic: silicone, glass, rubber, stainless steel, fibers (cellulose, polyester), etc. Extrinsic/process related: autoclave tape, gowning materials, Tyvek wrap, etc. Extrinsic/foreign: hair, insect parts, clothing fragments, metal, paint, etc. |
| Characterization | Symmetrical, asymmetrical/irregular, rigid, thick, thin, fragile, flexible, malleable, charged, chemical composition, metallic components, surface characteristics, bioreactivity, leachability, infectivity, sterility, infection risk |
| Source | Process related, foreign to process |
| Amount | Number per container, number of containers per lot |
| Manufacturing process mitigation | Point of filtration, particle reduction mitigation, sterilization procedures (terminally sterilized/aseptic processing), potential for detection [100% visual inspection, acceptable quality level (AQL), alert/action limits based on trend and statistical analysis] |
| Frequency of Detection | Inspection process and product and package attributes |