Surface engineering of particulates used in the quality control processes of the pharmaceuticals industry (with Mallinckrodt Pharmaceuticals)

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The Canadian pharmaceuticals industry, particularly its sub-sector on the preparation of parenteral (injected) drugs, is highly dependent on both automated and operator-driven visual inspection methods to detect the presence of foreign particulates or other defects. These inspection methods must be regularly validated to ensure appropriate quality control of the final products. As a result of recent significant improvements to the prefilled syringe process at the Mallinckrodt Pharmaceuticals plant in Pointe-Claire (Québec), the 500-um polymer beads used to challenge the visual inspection methods have been found to be too easy to detect. The company would like to challenge its validation processes using either smaller standardized polymer beads (150 um for immediate use, smaller particles to future-proof the process), or actual potential contaminants sampled from the process line. However, such smaller particulates suffer from dispersion issues: when they are placed within challenge syringes, they stick to the syringe walls, thus preventing detection from the motion-based automated sensors. The company has attempted (both in-house and with an outside contractor) to use surfactants to stabilize these challenge particle suspensions, but their efforts have been unsuccessful - the surfactants either have poor shelf life or lead to the stabilization of air bubbles (once again making the challenge syringes too easy to detect). Rather than use surfactants to stabilize the finer challenge particles, we propose a photochemical surface functionalization method (PICVD) developed at École Polytechnique de Montréal. This low-cost, scalable surface engineering method shows great promise to promote stable dispersion of fine particulates, thus providing significant cost savings to the company. The development of stable challenges syringes will be transferrable to a wide range of Canadian pharmaceutical companies, and the synthesis of "native contaminant" challenge syringes should prove to be a highly novel contribution to the state of the art.