Validation of Alternative Microbiology Methods for Product Testing Quantitative & Qualitative Assays

The validation of alternative microbiological methods for pharmaceutical testing is a very confusing topic, the more so as people use phrases such as “alternate sterility test” or “alternate microbial limits test.”What we have to agree to from the outset is that in fact we are not looking for “alternate” compendial tests.What most people actually mean is that we are looking for an alternative (and usually more rapid) means to determine whether a sample would meet the requirements of the compendial test. In most cases, the major components of the compendial test will be respected, it is only one or two particular aspects of the test that will be changed to increase the reliability or speed of the test. The sterility test by membrane filtration is an appropriate example.

To simplify this discussion, the compendial test is assumed to be the standard against which others are to be compared. But what does it mean to have an alternate sterility test? Should 50 samples be taken rather than 20? Increasing the sample size will result in a more sensitive test but also a fundamental change in the compendial test.However, this is not supportive of the goal of finding a real-time test that will provide a high degree of confidence that the sample will pass the compendial test. One could change the nominal porosity of the filter, arguing that a smaller pore will retain “small bacteria” and so presumptively result in a more sensitive test. Few people are arguing for this modification. Finally, one could change the method used to determine whether the filter has retained viable cells.

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