New requirements for pharmaceutical water in Europe

GMP News Nr. 114

GMP News
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

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. 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

Manufacture

Acceptable quality of water

Synthesis

Potable / Purified

Fermentation media

Potable / Purified

Recrystallisation / precipitationof sterile active ingredients

WFI

Used in formulation prior tosterile lyophilisation

WFI

Table 4: Non-sterileproducts

Manufacture

Acceptable quality of water

Synthesis

Potable / Purified

Fermentation media

Potable / Purified

Used in formulation prior tonon-sterile lyophilisation

Purified

Granulation

Purified

Extraction of herbal drugs

Purified**

** 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

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

 
 

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 AndreasMangel, CONCEPT HEIDELBERG

 

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