Particulate-Matter Content of D5/NS for Injection:Manufacturer Difference and Conformance with USP Limits

Abstract

The particulate contamination of one liter solutions of D5/NS for injection was determined by scanning electron microscopy. Three vendors were compared for differences in amount of particulates as well as for conformance with USP standards. Five empty plastic containers for two of these vendors were examined for their contribution to the overall particulate load after being filled with filtered Sterile Water for Injection through a 0.2-micron millipore filter.

Three containers from each of five lots from each of the three vendors were chosen at random for counting. A 20 mL sample from each liter was filtered through a polycarbonate membrane filter with a pore size of one micron. Sample preparation and filter mounting were conducted in a horizontal laminar flow hood. Particle counts were obtained with a Cambridge S180 scanning electron microscope using a field width of 110 microns. One hundred and fifty fields were examined for each sample. The solutions were compared for each of five separate particle size ranges.

Statistical analysis using multivariate analysis of variance did not prove a mean difference between the suppliers that would be clinically significant. All manufacturers met the USP standards for particles greater than 10 microns and would meet standards comparable to the British Pharmacopoeia’s for particles less than 10 microns. The empty plastic containers did not prove to be the major source of particulate matter. An occasional bag may prove to be more heavily contaminated than others in the same lot.

A finding that all three manufacturers exceeded the USP limits for particles over 25 microns suggests that the manufacturers’ quality control counting methods may be undersizing these large particles.