The methods used in most microbiological test laboratories originated in the laboratories of Koch, Lister, and Pasteur. As
such, they are very old, typically over a hundred years. While numerous changes have occurred in the chemistry laboratory,
there have been limited improvements in methods used for microbiological testing. In the past decade, the focus of many researchers
has been the study and implementation of improved methods for the isolation, early detection, characterization, and enumeration
of microorganisms and their products. In common language, this translates to better methods, automated methods, miniaturized
methods, and methods that require less time or expense.
All of these methods are collectively grouped into the category of rapid microbiological methods (RMM). In some compendia,
these are also called alternative microbiological methods. The methods range from simple dip-stick-type tests to very complex
automated systems that perform a variety of tests using a variety of techniques. The prices for these methods vary greatly,
from a few dollars to hundreds of thousands of dollars. Although these methods are called rapid microbiological methods, many
have their roots in other sciences, e.g., chemistry, molecular biology, biochemistry, immunology, immunochemistry, molecular
electronics, and computer-aided imaging.
Rapid microbiological methods provide significant opportunities for pharmaceutical companies to obtain data that may be significantly
better than that obtained via traditional methods, may be more cost effective, may provide marketing advantages, and may allow
for coordinated process analytical technologies to be fully integrated within a facility.
SLOW TO ADOPT NEW METHODS
While science moved forward in developing new microbiological methods, industry was slow to accept and implement these methods.
One of the greatest concerns was that regulators would not recognize these methods as superior to traditional ones. Another
concern was that companies would not be allowed to change test limits based upon the test method — i.e., they would use a
superior method that was likely to detect more organisms, and they would not be allowed to adjust limits to accommodate the
sensitivity of the new method. A further concern was that the first company to submit a new technology for regulatory approval
would have a much more difficult time obtaining approval than companies that submitted later.
REGULATORY FRAMEWORK
In recent years, a variety of documents has been issued or drafted to help the microbiologist select, purchase, implement,
and regulate the submission of rapid microbiological methods. We discuss six.
Parenteral Drug Association Technical Report Number 33
The Parenteral Drug Association (PDA) was one of the first organizations to develop guidance for evaluating, implementing,
and validating rapid microbiological methods. Guidance information was published as Technical Report 33 (PDA TR No 33).1 This document was developed by a committee of individuals from industry, regulatory agencies, compendial groups, and instrument
vendors. This guidance provided definitions, in microbiological terms, for validation criteria similar to the information
in United States Pharmacopeia (USP) <1225> for chemistry methods.2
USP Proposed Chapter <1223> on Alternative Microbiological Methods Validation
The USP proposed a draft monograph <1223>, Validation of Alternative Microbiological Methods, which defines various validation
criteria that may be used for rapid microbiological methods and defines these criteria in terms of microbiology. Additionally,
the proposal identifies how to determine which criteria apply to different technologies, based on the type of testing being
performed.3
