Cleanliness assessment of supplier-cleaned stoppers

The particulate levels found on supplier microcleaned rubber closures were compared to those of stoppers processed by a pharmaceutical manufacturer. The particle monitoring was performed using two official compendial methods: light blockage using a HIAC/ROYCO counter, and optical microscopy using a polarizing research microscope. The supplier-microcleaned stoppers were found to contain relatively few particles per stopper by both instrumental and microscopic counting. The cleaning process used by the pharmaceutical manufacturer was effective in reducing the particle load on their stoppers by factors of 2 to 20 fold as compared to the unwashed stoppers for the different size ranges measured. However, the supplier-microcleaned stoppers were found to be cleaner than those processed by the pharmaceutical manufacturer by a factor of 10 to 20 times for particle sizes greater than 10 microns using the instrumental method. Differences in the counts by microscopic and light blockage methods were attributed to the sampling and agitation procedures. Both the supplier-microcleaned and manufacturer's processed closures were found to meet the USP XXI limits for allowable particulate contamination in small volume parenterals.