Moving towards continuous monitoring of the microbial quality of water for pharmaceutical use
19/08/2020
Water for pharmaceutical use must be regularly tested for microbial load. Pharmacopoeias note the limitations of conventional control methods and recommend the use of other procedures to determine microbial quality. State-of-the-art technologies, such as flow cytometry, are paving the way for more efficient and faster microbiology.
Compliance with pharmacopoeia specifications (USP and European Pharmacopoeia)
Water is the most widely used raw material in almost every process in the pharmaceutical, cosmetics and biotechnology industries: it is used as an excipient in the reconstitution of medicines, as a basic element in the sterilisation of equipment and the sanitisation of systems, and in the cleaning of bottles and packaging. Because it is used both as a component of products and for production purposes, water comes into direct or indirect contact with substances likely to be absorbed. This is why French and European Good Manufacturing Practices (GMP) and pharmacopoeias (USP and Ph. Eur) have defined very strict standards and requirements for the production processes, physico-chemical and bacterial qualities and analysis methods of water for pharmaceutical use. These standards require manufacturers to carry out extensive treatment to ensure that process and utility water is fit for human consumption.
The limits of traditional microbial control methods
Pharmacopoeias distinguish between the quality of water for injection (WFI) and that required for purified water (PW). In all cases, however, they require regular monitoring of the bacterial load. They note the limitations of conventional control methods for identifying, counting and reporting the exact number of bacteria present in water for pharmaceutical use. In particular, they point to the strengths and weaknesses of the UFC2 microbial quality indicator, the reference for measuring the microbial quality of PW and WFI. The systematic enumeration of bacteria on Petri dish samples requires a five-day incubation period, resulting in a relatively slow, costly and even error-prone analysis. Manufacturers are therefore advised to use new processes to analyse the microbial quality of their water and identify contamination risks at an early stage.
Flow cytometry: accurate measurements and continuous monitoring
Among these new processes, flow cytometry paves the way for faster, more efficient microbiology. This now-proven technology consists of counting and characterising the cells and bacteria present in the water by passing them at high speed through a laser beam. Characterisation is based on the study of light re-emitted by fluorescence. This technique provides an accurate count of the microbial load (Total Cell Count, TCC) and nucleic acid content (HNA/LNA), where only 0.1 to 1% of pathogens are measured using the traditional method. Backed up by an online monitoring system, the process has a dual benefit: in addition to the accuracy of the analyses, the results can be obtained in just 20 minutes, allowing action to be taken as soon as the slightest discrepancy is identified.
Fast and connected, this alternative microbiology method also significantly reduces the risks of error and false positives associated with manual sampling, culture and storage. It also reduces the costs associated with regular sampling.
As a cutting-edge technology, flow cytometry paves the way for continuous validation of the microbial quality of PW (purified water) and WFI (water for injection) production systems, as well as more frequent checks on spot samples of water storage and distribution systems. This significantly improves the level of health safety (immediate detection of organisms, suspended particles, endotoxins, etc.) and operating efficiency of water treatment facilities in the pharmaceutical, cosmetics and biotechnology industries.