The need for new control strategies for particulate matter in parenterals

AbstractAn undesirable characteristic in lyophilized parenteral products is the potential presence of particulate matter in the final product, which may affects the patient safety. In this study, quality risk management tools described in the International Conference on Harmonization Guideline Q9 were used to estimate the risks for a pharmaceutical manufacturing line, based on three critical quality attributes: 1) visible particulate matter; 2) lyo-cake collapse traces; and 3) lyo-cake melt-back traces. Together with a Process Failure Mode Effect Analysis (PFMEA), an input-output analysis of the individual unit operations identified seven major material classes of extrinsic particulate matter. In addition to the process assessment, an experimental investigation of the location of impurities in lyophilized products was performed. To that end, intentionally contaminated vials were examined to locate the particulate matter and its possible migration. The results emphasize the importance of a full transmissio...