Reason for the invitation to the information exchange under experts was the discussion persisting since the 90s, to approve the manufacture of WFI via the membrane process in Europe as well - as it is basically approved in the US and in Japan. So far the concerns on the authority side have always been prevailing. For them the membrane process does not ensure microbiological safety, especially when using the reverse osmosis as main part of the processing.

Between 2004 and 2010 the three Pharmacopoeias Japan, USA and Europe collected quality data from membrane systems. However, not all of these systems worked solely with reverse osmosis but, e.g., in combination with ultrafiltration. The result showed that the values of the three studies regarding TOC, conductivity, endotoxin and total microbial count are comparable and correspond with the requirements of the European Pharmacopoeia. Interestingly another conclusion was that the currently valid specifications for WFI are far beyond the really measured values in membrane systems. The suitability of the limits originally intended for controlling WFI manufactured by distillation were thus questioned, just as the examination of the bacterial count through offline sampling. This method may be appropriate to find a massive bacterial load, but for single cells emitted by a biofilm this is questionable. Further discussed topics included the sampling of surfaces as well as the use of new microbiological methods like ultra fluorescence and flow cytometry. The addition of e.g. the monocytes activation test (MAT) for endotoxin examination was also addressed.

Conclusion: The EDQM is ready to discuss the approval of the membrane process for the manufacture of WFI, but probably not without combining it with limiting currently valid specifications and adding new testing methods at the same time.

Please also see the EDQM Report.

Author:
Dr Robert Eicher
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)