Panel Discussion

Visible and subvisible particles are critical quality attributes for parenteral products and must be monitored. A carefully designed, executed, and controlled drug product manufacturing process including a final 100% visual inspection and appropriate end-product controls ensures that visible particles are consistently minimized and demonstrates that the injectable DP is practically free from visible particles. To gather new data on particle visibility and shed light on this decade-old challenge, a global multi-company blinded visual inspection threshold study was conducted recently using several particle types of different sizes to determine the visibility limit. The study results provide key insights into limitations and challenges of visual inspection, namely, no universal visibility limit can be applied to all particle types as the detectability varies with particle type, number, and size. The study findings underscore the necessity of setting realistic expectations on size-based visibility limits in visual inspection, robust procedures for analyst training and qualification, and harmonization of guidelines globally. Similar to control of visible particles, subvisible particles are monitored, controlled, and minimized by optimizing the manufacturing process. Silicone oil which is a lubricant for prefilled syringes and some manufacturing accessories commonly used in biotherapeutics production can impact the subvisible particle count. The new findings of potential impact on immunogenicity (or lack of) from the recent silicone oil studies as well as the threshold of aggregates that can cause an immune response will be discussed.