Microorganisms compendial

Incubation time and temperature should be adjusted so that macroscopic microbial growth of a wide range of common isolates will be detected. This should be routinely demonstrated by including positive control imits inoculated with a low level of compendial microorganisms. Additional testing is desirable to demonstrate that the incubation time and temperature selected promote the growth of isolates obtained from machine operating environments. Incubation of 14 days at 25-32°C is recommended by the Pharmaceutical BFS Operators Association. 

The sterility test is applicable for determining whether drug substances, preparations, or other pharmacopeial articles are sterile as defined by the compendial method. A satisfactory result only indicates that no contaminating microorganisms have been found in the sample examined rmder the conditions of the test. Therefore, the result is a function of the efficiency of the adopted sampling plan. Compendial references to sterility testing include USP 24 Chapter (71) Sterility Tests the Ph. Eur. 3rd ed.. Biological Tests 2.6.1, Sterility and the JP Xlll 45, Sterility Test. 

As an alternative to compendial microorganisms, isolates frequently encountered in the manufacturing environment may be used to challenge the medium. 

A combination of compendial organisms and indigenous organisms may be used as controls. In all cases, however, microorganisms used in growth promotion testing should include both bacterial and fungal species. 

Data from newer technologies is challenging even the basic assumptions of the traditional definition of viability and the compendial approach to determining nonsterilily. Many types of common microorganisms, including E. coli, Salmo-nelia, and Streptococcus faecalis [2,3] have been shown to be capable of developing viable but nonculturable forms in stressed environments. 

Table 3 lists the sterilization cycle specifications currently recognized by the three major pharmacopoeias ( compendial cycles ). A body of knowledge exists to support the view that products that are properly exposed to any one of these compendial cycles will be free from all viable microorganisms. The origins of the compendial cycles are lost in history except to say that they were probably based on available technology (121 C is achieved by saturated steam held at a pressure of 15 lbs per inch, which is equivalent to 1 bar or one atmosphere). 

Doolan and coworkers [18] used three compendial recovery conditions to construct survival curves for naturally contaminated medical devices soybean casein digest medium incubated at 20-25 C, the same incubated at 30-35 C. and fluid ihioglycollatc medium incubated at 30-35 C for 14 days. Three tests for sterility therefore constituted the basis for observing the presence of viable microorganisms in three replicate conditions making up one sample. 

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