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Introduction
Rapid microbiology methods have long been essential tools of the clinical and food industry microbiology
laboratories. Swift diagnosis of infectious diseases by clinical labs and the need for prompt test results from
perishable food items have been strong incentives for the use of rapid methods. The pharmaceutical
industry, however, has not been as quick to embrace rapid microbiology despite the potential advantages.
Faster microbiology test results would provide better control over the manufacturing process. More rapid
microbiology assays would also allow for earlier release of product. One of the explanations offered by the
pharmaceutical industry for not using rapid microbiology methods is the uncertainty over regulatory
acceptance. The process of evaluating, validating and implementing rapid microbiology test methods can
be an expensive and time consuming task. Industry has been reluctant to expend precious resources when
regulatory approval of the new method may be in doubt.
This article will provide an overview of microbiology testing in the pharmaceutical industry and will look at
where rapid microbiological testing methods could fit into the manufacturing process. The issues involved
with validation of rapid microbiology methods will be considered with regard to CDER review expectations.
Finally, current FDA initiatives that could facilitate the use of rapid microbiology will be described.
Advantages of RMMs
The implementation of RMMs also provides interesting economic features, because of the significant
reductions in time to result over conventional methods. Normally, the production cycle is stopped or a
product is kept until checking the absence of contamination. If the time to result is shortened, the product
would be more rapidly released. Moreover, RMMs allow continuous sampling and data collection and
provide time-sensitive outputs and real-time data analysis. Therefore, more screenings and repeat tests
could be performed in all stages of production, improving the surveillance process.13 Real-time control and
early warning of contamination are essential before introducing raw materials and other product
components to the process, validating manufacturing, or distributing finished products.
RMMs involves an easy-to-handle protocol, with a negligible production of waste, minimal operator
variability, reduced staff training requirement, and possibility of automation. They also facilitate research
through generating earlier results. Moreover, the shorter analysis time reduces the probability of
contamination, improving the robustness. A shorter time to result facilitates replication of an analysis if a
contamination or a strange result occurs. Thus, RMMs can improve manufacturing consistency by
permitting faster implementation of corrective actions and fostering opportunities to improve the safety of
the process. Moreover, RMMs also show improved sensitivity, efficiency, selectivity, accuracy, high
throughput, and low false-positive rate, leading to higher efficiency.13 These features of RMMs provide an
opportunity to assess the significance of viable but nonculturable or stressed microorganisms.
The Four Key Benefits of Rapid Micro Methods

1. Considerable time-savings
   For an alternative method such as an RMM to be used as a replacement for a traditional method, the new
   technology must be validated and perform as well as, or superior to, the original method. In the case of
   RMMs, this superiority usually translates as faster time-to-result and increased efficiency.
   Traditionally, growth-based methods require growing microorganisms in media, which microbiologists must
   examine visually, looking for colony-forming units (CFU) in solid media types and measuring turbidity in
   liquid broths. Both of these processes can take days due to the limitations of the human eye—
   microorganisms must develop and become large enough for a microbiologist to be able to examine. RMMs,
   on the other hand, usually use markers that can be detected by an instrument at a low number of CFU. By
   eliminating the lengthy colony-forming step, RMMs are able to produce results much faster, even within
   hours.


2. Immediate reactions to contamination
   Corrective actions can be taken earlier because RMMs provide faster results, thus enabling a more
   proactive response to instances of microbial contamination and out-of-trend situations. With traditional
   methods, results can take days, making it difficult to pinpoint exactly when and where a contamination
   issue may have originated. Additionally, RMMs can assist in the design of more robust, automated
   processes that could reduce the opportunity for contamination altogether.


3. Financial savings and brand protection
   The speed and efficiency that RMMs can bring to an operation can have a significant effect on an
   organization’s bottom line. From a manufacturing perspective, a faster time to result can enable companies
   to release raw materials quickly, transfer in-process work to the next stage, and bring finished products to
   market, which can shorten the production cycle, reduce inventory requirements, and free up working
   capital.
   As mentioned above, RMMs offer the ability to quickly detect, control, and recuperate from contamination
   issues—and any delay in identifying a contamination event can have a major financial impact. Thus, the
   added speed and agility that RMMs offer may facilitate substantial financial savings and brand protection.


4. Optimization of staff time and labor Traditional microbiological methods are not only time-intensive, but labor-intensive. Automating key processes with RMMs can free up staff to focus on more impactful activities that can bring more value to the organization.
   Along the same lines, with automation usually comes enhanced objectivity. Some rapid methods can help laboratories reduce worker subjectivity, and automated systems that provide test results in a clear, pass–fail approach can take the guesswork out of plating and waiting.