Celsis' Rapid Microbiological Method (RMM) has been included in GlaxoSmithKline's (GSK) successful Veramyst New Drug Application (NDA), paving the way for broader acceptance of the time saving technique.
The inclusion of Celsis' RMM as part of GSK's Veramyst (fluticasone furoate) nasal spray submission is the first time a pharmaceutical company has referenced the technology in an NDA as the end product testing method to ensure that the final product is microbe free.
The technology, which reduces the microbial assay time from a week to a day, has seen widespread use in the consumer goods industry; however the pharmaceutical industry has been somewhat reluctant to incorporate the test into NDA testing protocols.
Celsis believes this relative reluctance was due to the pharmaceutical companies being unclear on the regulatory requirements for the validation of RMM and uncertain of regulator's acceptance of alternative methods.
The method has been used in a number of post-market supplements or appendices after a drug had been approved.
"This approval by the FDA is demonstrating the growing acceptance of regulatory agencies for these methods; globally RMM detection methods have been recognised by regulatory agencies but this is the first NDA where the RMM is specified," said Dr Diane Younker, manager of global regulatory affairs at Celsis.
"For companies considering implementing a RMM they should feel fairly comfortable that the regulatory agencies will accept these methods and that the validation process is fairly straightforward."
Within the last year both the United States Pharmacopeia (USP) and the European Pharmacopeia (EP) have released official chapters that describe how to validate the method, with the FDA also providing guidance on the process for validation and submission.
"Outside of end product testing the technology has huge potential in testing raw materials and in-process testing," said Dr Younker.
"This is especially important in biologics manufacturing as the products are very high value and if there is a contamination event you need to detect it as quickly as possible to minimise revenue loss."
The company has developed an assay to specifically address the needs for in-process testing in the bioprocessing industry, the RapiScreen Biologics test which pretreats the sample to reduce non-microbial sources of ATP to deliver results in 24 hours or less.
The technology uses the same chemical reaction to detect the presence of microbes as what causes a firefly's tail to glow - bioluminescence.
The reaction occurs when luciferase and luciferin come in to contact with the adenosine triphosphate (ATP) which is present in all living organisms. The reaction releases light which can then be detected using a sensitive light detector known as a luminometer.
Celsis has enabled this well known reaction to be used in a broad range of manufacturing industries by developing selective extraction agents.
In addition, the company has also developed an even more sensitive method which uses the enzyme Adenylate Kinase (AK) to generate ATP from the microbes, further enhancing the sensitivity of the technique as well as increasing the speed of the test dramatically.
The company claims that as a general guide, the AK enzyme can be made to produce approximately 40 times more ATP in one minute than the bacterium originally contained.
The most common method of testing for sterility is the USP's Microbial Limit Test which can take up to 7 days to produce a result; in contrast, the RMM using AK can be as quick as 18 hours.
According to Dr Younker, the test workflow is relatively simple and does not need a trained microbiologist to perform the assay.
A sample is simply incubated in a microbial broth - in many cases the same broth that was used for a company's traditional method.
A portion of the sample is then placed in a cuvette and loaded in the liminometer which can hold up to 164 samples.