Whyte W, Niven L, Bell N D
J Parenter Sci Technol. 1989 Sep-Oct;43(5):208-12.
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.
对43种小容量产品（主要是注射剂）进行了无菌灌装药品支持微生物生长能力的测试。这些产品接种了多种已知与药品污染相关的微生物。一般来说，发现革兰氏阴性菌比革兰氏阳性菌更易生长。几个细胞的接种物有可能繁殖到高达10(7)/mL的水平。防腐剂的存在也影响生长的可能性，19种无防腐剂药品中有12种（63%）支持一种或多种微生物生长；有防腐剂的24种药品中只有3种（12%）支持生长。结合无菌灌装产品的配方、环境采样和生产所需洁净室条件的质量，讨论了这些观察结果的重要性。建议对于那些设计为无菌但非最终灭菌的药品，在生产开始前应测试其支持微生物生长的能力。通过这种方式，可以确定无菌灌装所涉及的风险。提出了一种测试方法，其中“指示”微生物将预测药品制剂支持生长的可能性。
