22/23 April 2021
GMP News Nr. 114
2 July 2001
Newrequirements for pharmaceutical water in Europe
For some years now already thediscussion concerning manufacturing methods for WFI (water for injection)has also got underway as regards American and Japanese requirements.
In 1999, at an internationalmeeting in Strasbourg the requirement for the use of reverse osmosis tomake WFI was rejected owing to lack of data. Distillation therefore isstill the only permissible manufacturing procedure in Europe formanufacturing WFI.
During the meeting a guideline forthe use of the various pharmaceutical water qualities was consideredhelpful. Another result of the meeting was the water monograph “HighlyPurified Water”, as a third water quality, due to enter into effect on1.1.2002.
As the basis for all pharmaceuticalwater qualities, drinking water is specified whose quality requirementsare not, however, defined by pharmaceutical codes but by EU Directive80/778/EC.
The water qualities “PurifiedWater” and “Water for Injection” are known. The new water quality“HPW - Highly Purified Water” is intended for preparations requiringwater of high microbial quality but not WFI. The test requirements for HPWare the same as those for “Purified Water”, supplemented by the testfor bacterial endotoxins.
HPW also meets the qualityrequirements of WFI but does not require distillation as the manufacturingmethod. A possible manufacturing method is, for instance, two-stagereverse osmosis combined with ultrafiltration or electrodeionization.
While the chemical quality controlof water does not present many problems, the microbial quality controlmust be regarded critically. Owing to the long years of experience withdistillation as a manufacturing method for WFI and the possibility ofvalidating distillation as a “single plant” this manufacturing methodstill has a considerably greater microbial safety than other possiblealternative methods.
Furthermore the qualification andvalidation of water generation, storage and distribution form aparticularly important part of GMP and should also be an integral part ofeach inspection.
Generally, the use of the variouspharmaceutical water qualities should be made dependent on the productrequirements. The guideline makes some general statements about thisdivided into “water as a product component” and “water used forproduction”:
Water asa product component
Table: Sterile Products
Table 2: Non-sterile Products
*In certain disease states eg. Cysticfibrosis, medicinal products administrated by nebulisation are required tobe sterile and non-pyrogenic. In such cases WFI or sterilised HPW shouldbe used.
** For some products such as veterinaryteat dips it may be acceptable to use potable water where justified takingaccount of the variability in chemical composition and microbiologicalquality
Waterused in production
Table 3: Sterilematerials / products
Table 4: Non-sterileproducts
** The use of potable water may beacceptable, where justified. The Applicant would need to demonstrate thatpotential variations in the water quality with respect to mineralcomposition, would not influence the composition of the extracts
Table 5: Water forcleaning
Remark: The Draft Guideline"Note for Guidance on Quality of Water for Pharmaceutical Use"has the following time schedule: