GMP News Nr. 114
2 July 2001
New requirements for pharmaceutical water in Europe
For some years now already the discussion concerning manufacturing methods for WFI (water for injection) has also got underway as regards American and Japanese requirements.
In 1999, at an international meeting in Strasbourg the requirement for the use of reverse osmosis to make WFI was rejected owing to lack of data. Distillation therefore is still the only permissible manufacturing procedure in Europe for manufacturing WFI.
During the meeting a guideline for the use of the various pharmaceutical water qualities was considered helpful. Another result of the meeting was the water monograph Highly Purified Water, as a third water quality, due to enter into effect on 1.1.2002.
As the basis for all pharmaceutical water qualities, drinking water is specified whose quality requirements are not, however, defined by pharmaceutical codes but by EU Directive 80/778/EC.
The water qualities Purified Water and Water for Injection are known. The new water quality HPW - Highly Purified Water is intended for preparations requiring water of high microbial quality but not WFI. The test requirements for HPW are the same as those for Purified Water, supplemented by the test for bacterial endotoxins.
HPW also meets the quality requirements of WFI but does not require distillation as the manufacturing method. A possible manufacturing method is, for instance, two-stage reverse osmosis combined with ultrafiltration or electrodeionization.
While the chemical quality control of water does not present many problems, the microbial quality control must be regarded critically. Owing to the long years of experience with distillation as a manufacturing method for WFI and the possibility of validating distillation as a single plant this manufacturing method still has a considerably greater microbial safety than other possible alternative methods.
Furthermore the qualification and validation of water generation, storage and distribution form a particularly important part of GMP and should also be an integral part of each inspection.
Generally, the use of the various pharmaceutical water qualities should be made dependent on the product requirements. The guideline makes some general statements about this divided into water as a product component and water used for production:
Water as a product component
Table: Sterile Products
Table 2: Non-sterile Products
*In certain disease states eg. Cystic fibrosis, medicinal products administrated by nebulisation are required to be sterile and non-pyrogenic. In such cases WFI or sterilised HPW should be used.
** For some products such as veterinary teat dips it may be acceptable to use potable water where justified taking account of the variability in chemical composition and microbiological quality
Water used in production
Table 3: Sterile materials / products
Table 4: Non-sterile products
** The use of potable water may be acceptable, where justified. The Applicant would need to demonstrate that potential variations in the water quality with respect to mineral composition, would not influence the composition of the extracts
Table 5: Water for cleaning
events on the topic of pharmaceutical water:
Remark: The Draft Guideline
"Note for Guidance on Quality of Water for Pharmaceutical Use"
has the following time schedule: