Water for injection (WFI) may be obtained nowadays by one of the following ways:
Thermal distillation, single or multi-effect, is the most popular method of Water For Injections (WFI) generation in Europe. The main advantage of this method is the reliability resulting from the design simplicity in which moving parts are not used in the process of WFI water generation. Due to the fact that the process is carried out at high temperature, this method gives complete confidence in the microbiological purity of the water obtained.
The source for WFI generation by thermal distillation is usually Purified Water. The feed water for the thermal distiller must meet at least the European Pharmacopoeia quality attributes for the PW. However, it is recommended that the feed water meets USP PW quality requirements. Feed water should contain the lowest possible concentration of non-condensable gases. The best quality of feed water will certainly extend the life of the distiller, as well as reduce the frequency of service associated with unit cleaning/derouging and/or repairing.
The process of thermal distillation is basing on evaporation and subsequent condensation of the feed water. The source of energy used to heat and evaporate the water in the process of thermal distillation can be technical steam under pressure of 4-8 bar or electric energy. In fact, electric distillers are used only for equipment of small capacity, usually not exceeding 200 L/h.
Thermal distiller for Water For Injections generation may consist of one or more, from 2 to 8, evaporation columns. The number of distillation columns also determines the number of distillation effects (therefor, the term "multi-effect distillation"). The increase in the number of columns leads to decrease of utilities consumption, and consequently, the operating costs of the unit decrease, while the investment costs increase. Equipment of small capacity - up to 100 L/ h - are most often designed as single-effect units. The bigger the WFI capacity of the unit is, the number of distillation effects is usually higher.
Water For Injections cold mode of generation using membrane methods has been approved for many years in the United States. Until now, European legislation has been more conservative, considering distillation the only acceptable method of obtaining WFI. However, Supplement No. 9.1 to the European Pharmacopoeia as of April 2017 allowed using methods other than distillation for the production of Water for injections. This document lists: single- and double-stage reverse osmosis in combination with electrodeionization, ultrafiltration, or nanofiltration.
Given the need of almost complete desalination of water in the process of WFI generation and ensuring complete microbiological purity, the optimal cold WFI production line will most often consist of the following purification steps: reverse osmosis - electrodeionization - ultrafiltration. Depending on the degree of salinity in the feed water, the reverse osmosis section can be single- or double-stage. Feed water for reverse osmosis, of course, must be preliminarily subjected to an appropriate pre-treatment process, just like for PW generation systems.
In all cases membrane methods are used to generate Water For Injections in cold process, special attention should be paid to the careful design of periodic sanitation process. Cold processes are always more exposed to risk of microbiological contamination than traditional thermal distillation. Periodic sanitation of cold WFI generation equipment should be carried out on regular basis, preferably by thermal method.
Despite the recent changes in the standards of the European Pharmacopoeia, most likely, thermal distillation will remain the most common method to generate Water for Injection due to its reliability and microbiological safety. However, generation of WFI by the means of membrane technologies may be an interesting alternative, especially when there is no industrial steam in the facility available or when the process requires bringing cold WFI to the points of use. In this case, it is worth considering to combine the generation of WFI in cold mode with storage and distribution under ozone generated by a pharmaceutical electrolytic ozone generator.