Cundell Anthony M, Chatellier Sonia, Schumann Peter, Lilischkis Richard
Merck Research Laboratories, Union, New Jersey, USA.
PDA J Pharm Sci Technol. 2010 Mar-Apr;64(2):137-55.
The pharmacopoeias list a number of microorganisms to be used in the compendial microbiological tests for confirming the growth-promoting, indicative, and inhibitory properties of the media and demonstrating the suitability of the test for a specific test article. Major national culture collections are specified as the sources for these test strains based on their history of deposition and maintenance and use in the compendial tests. Using these microorganisms, it has long been assumed that these strains are interchangeable and that sourcing the strains from different culture collections has no impact on the result of the media quality control and method qualification tests. In order to evaluate whether this assumption is correct and to add more certainty to the procedures, we investigated whether there are detectable differences among isolates of the same strain sourced from different culture collections. Using various phenotypic and genotypic identification and strain typing methods, nine major pharmacopoeial species were analyzed. As expected, most of the species showed very uniform patterns across the isolates, indicating that the strains were indeed identical. Surprisingly, the strains of Salmonella enterica subsp. enterica serotype abony showed distinct differences at both the genotypic and the phenotypic level, suggesting that the strains sourced from the different culture collections were not identical strains, or that they have undergone detectable genetic shift from the time they were derived from the original depositor. Irrespective of the level of genotypic or phenotypic homology identified here, there are no practical consequences on their performance in compendial assays. It is concluded that the compendial strains investigated in this study are indeed equivalent and will perform identically in compendial tests, making it safe to base pharmaceutical quality control procedures on the strains sourced from any of the recognized national culture collections.
各国药典列出了一些微生物，用于药典微生物检验，以确认培养基的促生长、指示和抑菌特性，并证明该检验方法对特定供试品的适用性。主要的国家菌种保藏中心被指定为这些试验菌株的来源，这是基于它们的保藏、维护历史以及在药典检验中的使用情况。长期以来，人们一直认为使用这些微生物时，这些菌株是可互换的，并且从不同菌种保藏中心获取菌株对培养基质量控制和方法验证试验的结果没有影响。为了评估这一假设是否正确，并使程序更具确定性，我们研究了来自不同菌种保藏中心的同一菌株的分离株之间是否存在可检测到的差异。使用各种表型和基因型鉴定及菌株分型方法，对9种主要的药典规定菌种进行了分析。正如预期的那样，大多数菌种在分离株中表现出非常一致的模式，表明这些菌株确实是相同的。令人惊讶的是，肠炎沙门氏菌亚种肠炎血清型阿博尼菌株在基因型和表型水平上均表现出明显差异，这表明来自不同菌种保藏中心的菌株并非相同菌株，或者它们自从原始保藏者获得后发生了可检测到的基因变化。无论此处鉴定的基因型或表型同源性水平如何，它们在药典分析中的性能都没有实际影响。结论是，本研究中所研究的药典规定菌株确实是等效的，并且在药典检验中表现相同，因此基于来自任何认可的国家菌种保藏中心的菌株进行药品质量控制程序是安全的。
