Microbial growth in small-volume pharmaceuticals.
The ability of aseptically filled pharmaceuticals to support microbial growth was tested on 43 small-volume products (mainly parenterals). These were inoculated with a variety of microorganisms which were known to be associated with contamination of pharmaceutical products. In general, Gram-negative bacteria were found to be much more likely to grow than Gram-positive. It was possible for an inoculum of a few cells to multiply to levels up to 10(7)/mL. The presence of preservatives also influenced the likelihood of growth, 12 out of 19 (63%) of the pharmaceuticals without preservatives supporting growth of one or more microorganisms; only 3 out of 24 (12%) of those with preservatives supported growth. The importance of these observations is discussed with reference to formulation of aseptically filled products, environmental sampling and the quality of cleanroom conditions necessary for production. It is suggested that those pharmaceuticals which are designed to be sterile but not to be terminally sterilized, should be tested before production begins, for their ability to support microbial growth. In this way, the risks involved in aseptically filling can be ascertained. A test is proposed in which "indicator" microorganisms would predict the likelihood of pharmaceutical formulations supporting growth.
Whyte
W
W
Niven
L
L
Bell
N D
ND
D004340:Drug Contamination; D006090:Gram-Negative Bacteria / Q000254:growth & development*; D006094:Gram-Positive Bacteria / Q000254:growth & development*; D006801:Humans; D007263:Infusions, Parenteral