Evaluation of acceptance criteria for particulate limits for small-volume parenteral products.

The precision of and correlation between the USP membrane filtration-microscopic method and the instrumental method for sizing and quantifying particulate matter in small-volume parenteral products were determined using simulated products. The total variance for the instrumental counts was lower than the USP method for all products in the 10--25-mum particle range and for most products in the greater than or equal to 25--50-mum range. A linear relationship between the instrumental counts and the USP counts was demonstrated for the 10--25-mum particle range. However, the instrumental reading was higher than the USP method for counts of 10 or more particles/ml. The instrumental and the USP methods failed to correlate on particulate sizes greater than 25 mum. The content of particulate matter in over 100 small-volume parenteral products was sized and quantified by the USP and the instrumental methods. From the instrumental data, a statistical treatment for the analysis of particulate data is presented as an objective method of evaluating acceptance criteria on particulate matter in small-volume parenteral products.