Is purified water pH neutral

The quality is decisive

In addition to the European Pharmacopoeia, the requirements of the Drinking Water Ordinance also have a decisive influence on the quality of the pharmaceutically used water, since drinking water can be used as a raw material for the production of the water qualities mentioned in the Ph. Here, requirements are made with regard to the microbiological and chemical quality, for example the absence of pathogens, limit values ​​for heavy metals, biocides and other known toxic substances. However, the investigation of the microbial contamination of drinking water is carried out on a different agar than that prescribed for pharmaceutical purposes. The recovery of germs is significantly lower with the agar used in drinking water analysis. Therefore, limit values ​​and test results from this area cannot be directly compared (9).

Manufacture of water for pharmaceutical purposes

The importance of water in pharmaceutical production is expressed not least in the fact that both the European Medicines Agency (EMA) and the World Health Organization (WHO) comprehensively regulate the production, quality and use of pharmaceutically used water in guidelines (8, 11 , 12).

As a raw material for the production of purified water or WFI, the Ph. Eur. Allows drinking water, the quality of which is regulated in Germany by the Drinking Water Ordinance. Purified water can be produced by means of distillation, ion exchange processes, reverse osmosis or other suitable processes. Only distillation is allowed for the production of Aqua ad iniectabilia (1, 2).

Distillation: The basic principle of distillation is the evaporation of water and the condensation of the water vapor in a separate vessel. During this process, aerosols are always created that carry away non-volatile components such as salts, organic compounds or microorganisms from the raw water. Therefore, the requirement for apparatus for the production of WFI that entrainment of droplets must be avoided, for example through so-called baffles in the still, on which small droplets are deposited. Overall, distillation is an energy and cooling water-intensive process. In larger technical systems, heat exchangers and compressors are therefore used to save energy and cooling water.

In general, very good water quality can be produced by means of distillation. By heating it, almost germ-free water can be produced. It is important - especially for small-scale production in pharmacy laboratories - to collect the distillate in a sterile or low-germ storage container in order to avoid unnecessary decanting processes and the associated risks of contamination (2, 6).

Ion exchanger: Ion exchange processes are common methods for the production of aqua purificata. Here, the ionic components of the water on cation and anion exchange resins against hydrogen (H.+) and hydroxyl ions (OH), which react with each other to form water. This results in demineralization, but no removal of organic substances.

The resulting water quality can be recorded using conductivity measurement as an in-process or final control. In addition to ionic components, organic impurities (total organic carbon, TOC) must also be removed in order to comply with the pharmacopoeia requirements for aqua purificata. Through photo-oxidation, in which ozone is generated by UV radiation (100 to 400 nm), organic material can be converted completely into CO2 and H2O are oxidized.

Water from ion exchange systems is generally to be viewed as microbially critical, as there are no germicidal processes during production. Ion exchange resins are organic polymers with a porous and very large surface. This offers microorganisms simple opportunities to establish themselves and build up biofilms. In addition, the water flowing through is at room temperature and carries organic substances with it that can serve as a nutrient base. In short: ideal conditions for the growth of microorganisms. Therefore, water from ion exchangers must be pretreated before use. This can be done by filtration through a bacteria-retaining filter with a nominal pore size of maximum 0.22 µm or by boiling for at least five minutes.

It should be noted that killing viable microorganisms by boiling does not improve the endotoxin content, since bacterial endotoxins in particular are usually stable up to 250 ° C. Endotoxins act as pyrogens and, when administered parenterally, can lead to fever reactions and sepsis, even in very small amounts. They mostly belong to the group of lipopolysaccharides, which are components of the cell walls of gram-negative bacteria. Other materials, for example plastic components, can also have a pyrogenic effect. For parenterals in particular, it is essential to limit pyrogens and to use WFI (1, 6).

Reverse or reverse osmosis: Reverse osmosis is also used to produce aqua purificata. The principle: two chambers are separated from each other by a semipermeable membrane that is only permeable to water molecules. If pressure is built up on the side of the chamber in which the raw water is located, the water molecules diffuse through the membrane into the area that collects the pure water.