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PHARMACEUTICAL INDUSTRY

high quality is standard

RMM AT PHARMACEUTICAL COMPANIES

Rapid and sensitive detection and quantification of microbial contamination is of utmost importance for Pharmaceutical and biotechnology companies. Process monitoring, including compound testing, product testing, environmental monitoring and WFI analyses, is key for highest quality of pharmaceutical and biotech end products.

To meet the high industry standards with low limitations of bioburden, large volumes need to be evaluated for microbial contamination to enable reliable analysis. Each Rapid Microbial Method used must be highly sensitive, applicable for larger volume testing and reliable, giving same day results.

The MuScan(TM) technology meets these requirements.

VALIDATION OF MUSCAN(TM) TECHNOLOGY

The Sieve-ID(TM) method with MuScan(TM) analysis is validated according to USP[1223] and Ph.Eur 5.1.6 at Innosieve Diagnostics, but is also being internally evaluated and validated at major pharmaceutical companies. The results show to be at least non-inferior to the compendial methodology for bioburden testing. All pharmacopoeia recommended reference strains have been evaluated, giving great precision and highly reliable quantification. The overall limit of reliable detection was found to be 1-5 FFU per volume with accurate quantification up to high contamination levels.

A comparison of a direct rapid method like the MuScan(TM) method with a reference growth-based method requires additional statistical needs and experimental approaches. As a growth-based method measures the counts in CFU (Colony Forming Units), the number of counts is highly dependent on growth parameters like pH, nutrients, temerature etc. Next to that, a microbe might be dormant or as so-called VBNC (Viable but Non Culturable) and will thus not form a colony. This is in high contrast with a direct microbial method, as these measure in FFU (Fluorescense Forming Units). All microbes that are viable are detected, including VBNCs. As of this contrast, during validation studies good care should be taken in experimental design to avoid misinterpretation of either methods.

At Innosieve we have put much emphasis on proper approaches to compare the growth-based compendial method with our direct MuScan method. These include the essential criteria specificity, sensitivity, accuracy, precision, robustness and ruggedness. Even when using artificial microbial spiking studies, the MuScan method has shown to be at least non-inferior to the compendial method.


SEE WHAT IS REALLY THERE

A growth-based method will grow microbes that can proliferate under the used environmental conditions and present nutrients. If conditions don’t match the microbial requirements for growth, that particular microbial species or strain will not show growth and will lead to an underscore or even a false negative result.

The MuScan method is not dependent on cell growth. The direct method simply detects and quantifies the number of microbes present in a sample. As it is not growth-based, the environmental conditions are not relevant and there is no limitation due to required presence of nutrients. The MuScan method will actually show all viable cells in a sample. No high underscore or missing of cells but an accurate quantification of present viable microbes.

Reference: Relationship between the Viable but Nonculturable State and Antibiotic Persister Cells. Mesrop Ayrapetyan, Tiffany Williams, James D. Oliver. Journal of Bacteriology Sep 2018, 200 (20) e00249-18; DOI: 10.1128/JB.00249-18

In another study, water samples were analysed using the compendial method R2A / TSA plating and the MuScan(TM) method. The MuScan(TM) method revealed a 1-2 log more viable cells compared to the growth-based method. NGS analysis on these water samples indicated high microbial diversity where TSA showed a low diversity. Only a small portion of microbial water organisms was able to grow on TSA or R2A. The MuScan(TM) method detects the microbes that can grow on plate, but also the large portion of VBNCs.


VALUE OF A RAPID MICROBIAL METHOD

For each company, the value of a RMM can be different. Where one company is requiring an intermediate testing of compounds before mixing, another company is using the RMM for testing the cleaning efficiency of a bio-column. A next company will use the RMM for process monitoring and trend analysis, while the other will use it for environmental testing or product testing.

Either case, the requirement for implementing a RMM is that it must provide an additive value. Upon implementation the additive value of an RMM is often shown quickly in two improvements: saving money and increasing speed of analysis. In many cases the application of an RMM method will lead to a rapid return on investment and saving costs. Therefore a RMM can be of high interest for each company producing high value products.

The MuScan method provides all of the mentioned needs. No concessions are made in view of sensitivity, quantification, speed or ease of use. All without the need for microbial growth. Next generation RMM.

Are you interested in our RMM for the direct detection and quantification of microbes in your products within 1 hour?

Let's discuss!