New requirements for pharmaceutical water in Europe

GMP News Nr. 114

GMP News
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

Sterile medicinal products

Acceptable quality of Water

Parenteral

WFI

Ophthalmic

HPW

Haemofiltration Solution
Haemodiafiltration Solution

WFI

Peritoneal Dialysis Solutions

WFI

Irrigation Solutions

WFI

Nasal / Ear Preparations

HPW

Cutaneous Preparations

HPW

Table 2: Non-sterile Products

Non-sterile medicinal product

Acceptable quality of Water

Oral Preparations

Purified

Nebuliser Solutions

Purified*

Cutaneous Preparations

Purified**

Nasal / Ear Preparations

Purified

Rectal / Vaginal Preparations

Purified

*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

Manufacture

Acceptable quality of water

Synthesis

Potable / Purified

Fermentation media

Potable / Purified

Recrystallisation / precipitation of sterile active ingredients

WFI

Used in formulation prior to sterile lyophilisation

WFI

Table 4: Non-sterile products

Manufacture

Acceptable quality of water

Synthesis

Potable / Purified

Fermentation media

Potable / Purified

Used in formulation prior to non-sterile lyophilisation

Purified

Granulation

Purified

Extraction of herbal drugs

Purified**

** 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

Cleaning / Rinsing of Equipment, Containers, Closures

Acceptable quality of water

General use including CIP

Purified

Initial rinse of containers / closures for sterile products

HPW

Final rinse of containers / closures for sterile parenteral products

WFI

Final rinse of containers / closures for sterile non-parenteral products

HPW

 

Upcoming events on the topic of pharmaceutical water:

GMP-/FDA-compliant Pharmaceutical Water Systems, September 26-27, 2001 in Uppsala, Sweden
Including a tour of Fresenius Kabi Uppsala
 

Remark: The Draft Guideline "Note for Guidance on Quality of Water for Pharmaceutical Use" has the following time schedule:
10/00 - 01/01      Discussion in the QWP
02/01                 Transmission to the CPMV/CVMP
02/01                 Release for consultation
08/01                 Deadline for comments

Author: Dr Andreas Mangel, CONCEPT HEIDELBERG

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