Cleanliness assessment of supplier-cleaned stoppers.

Area of Science:

• Pharmaceutical manufacturing
• Materials science
• Analytical chemistry

Background:

• Particulate contamination in pharmaceutical closures is a critical quality attribute.
• Ensuring low particle counts on rubber stoppers is essential for parenteral drug safety.
• Existing cleaning processes require rigorous evaluation for particle reduction efficiency.

Purpose of the Study:

• To compare particulate levels on supplier microcleaned rubber closures versus those processed by a pharmaceutical manufacturer.
• To evaluate the effectiveness of different cleaning methods in reducing particle load on stoppers.
• To assess compliance with United States Pharmacopeia (USP) XXI particulate contamination limits.

Main Methods:

• Particle monitoring using light blockage (HIAC/ROYCO counter) and optical microscopy (polarizing research microscope).
• Comparison of particle counts between unwashed, manufacturer-processed, and supplier-microcleaned stoppers.
• Analysis of particle distribution across different size ranges.

Main Results:

• Supplier-microcleaned stoppers exhibited significantly lower particle counts than manufacturer-processed stoppers, especially for particles >10 microns (10-20 times cleaner by instrumental method).
• The pharmaceutical manufacturer's cleaning process reduced particle load by 2-20 fold compared to unwashed stoppers.
• Both cleaning methods resulted in stoppers meeting USP XXI limits for particulate contamination.

Conclusions:

• Supplier microcleaning offers superior particle reduction for rubber closures compared to standard pharmaceutical manufacturer processing for larger particles.
• Both evaluated methods achieve compliance with USP XXI particulate limits.
• Discrepancies between instrumental and microscopic methods highlight the impact of sampling and agitation procedures on particle detection.