Abstract

Currently, limited guidance is available for the contamination control of visible particles for the manufacture of sterile devices; thus, a comprehensive guidance is warranted. Sterile devices require stringent control of visible particulates to ensure proper functionality, performance assurance of sterility, reliability, patient safety, efficacy, and product quality. This paper outlines practical and science-based strategies to prevent/minimize visible particle contamination from non-process related extrinsic and process related intrinsic sources. Witness plates are proposed as a comprehensive strategy for the real time detection of visible particles, sources of extrinsic and intrinsic visible particles, and methods to identify particle types. Implementing the control measures described herein, which include air ionization units for the control and neutralization of static charges, would maximize device yield and quality, thus reducing rework and leading to increased profitability. Installing validated air ionization systems at appropriate manufacturing and processing locations, storage, product transfer areas, and gown-up rooms can significantly reduce visible particle contamination accumulation, dispersion, and yield losses. Implementing effective material transfer practices can further minimize the risk of introduction of unwanted particles and particle dispersion within classified areas. Also described are additional control measures, such as material systems and supply chain controls, good facility design, gowning practices, manufacturing equipment and tool controls, and manual visual inspections which would further contribute to the overall reduction of particle burden. Crucial elements of an effective particle removal process are the dry and wet cleaning processes and the facility surveillance program. Process-product-particle traceability matrices can serve as effective tools to promptly identify trends and reduce device conformity defects. For this paper, the meaning of the term particle only includes particulates and particulate matter. Microbial contamination control approaches, including facility decontamination, are outside the scope of this paper.