28/29 April 2021
According to the European Pharmacopoeia, it has been possible to produce water for injection (WFI) using non-distillation methods since March 2017. The WHO has now published a new guideline on this subject for comment. The draft document entitled "PRODUCTION OF WATER FOR INJECTION BY MEANS OTHER THAN DISTILLATION" doesn't contain any significant innovations compared to the WFI Monograph (0169) itself or the Q&A document of the EMA.
The text contains few technical details, but it is said that the combination of reverse osmosis (double-pass) with ultrafiltration, softening, pre-filtration and degasification can be useful. All parts of the system should be suitable for routine sanitization, including reverse osmosis membranes. The text refers to thermal, chemical methods or a combination of both methods. WFI should be produced from drinking water or purified water (PW). It shall be demonstrated that the purification process of distillation is comparable or better. The integrity of the membranes should be checked regularly. In addition, in-line monitoring should be provided, without specifying which parameters are to be considered here (conductivity, TOC, microbiology?).
The document mentions the term "no risk" several times, i.e. that non-distillation production does not pose a risk of contamination of the WFI (5.4, 6.1, and 7.7). However, a "no risk" or "0 risk" requirement is not practicable. In paragraph 6.2, however, this is somewhat mitigated. It states that the risk must be reduced to an acceptable level.
The draft can be commented on until 15 April 2019.
For further details please see the WHO Guideline " PRODUCTION OF WATER FOR INJECTION BY MEANS OTHER THAN DISTILLATION" - also to be found on the WHO website under Current Projects.