WHO-TRS1033-ANNEX 3 Water for Pharmaceuticals Use

Unlike other product or process ingredients, water is usually drawn from an on-demand system and is not subject to testing and batch or lot release prior to use. Thus it is essential that water quality (including microbiological and chemical quality) throughout production, storage and distribution processes is controlled.

In recent years, following extensive consultations with stakeholders, several pharmacopoeias have adopted revised monographs on water for injection (WFI) that allow for production by non-distillation technologies. In 2017, the World Health Organization (WHO) Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) recommended that the WHO Secretariat collect feedback on whether or not they should revise the WHO specifications and good manufacturing practices (GMP) on WFI and, if so, how to do so. Following several consultations, the ECSPP agreed that the monograph in The International Pharmacopoeia (Water for injections) and the guideline WHO Good manufacturing practices: water for pharmaceutical use (1), should both be revised to allow for technologies other than distillation for the production of WFI. 

In early 2019, the WHO Secretariat commissioned a draft guidance text for the production of WFI by means other than distillation. Following several public consultations, the text was presented to the Fifty-fourth ECSPP. The Expert Committee adopted the Production of water for injection by means other than distillation guideline and recommended that it should also be integrated into WHO’s existing guideline on Good manufacturing practices: water for pharmaceutical use. 

This document is a revision of WHO Good manufacturing practices:

water for pharmaceutical use, previously published in the WHO Technical Report Series, No. 970, Annex 2, 2011.

Introduction and scope

1.1 This document concerns water for pharmaceutical use (WPU) produced, stored and distributed in bulk form. It provides information on different specifications for WPU; good practices for the management of the quality of water systems; water treatment (production) systems; water storage and distribution systems; commissioning, qualification and validation; sampling and testing; and the routine monitoring of water.

1.2 The focus of this document is on the treatment, storage and distribution of treated water used in pharmaceutical applications. It excludes the production, storage and usage of water in quality-control laboratories. 

1.3 This document does not cover water for administration to patients in the formulated state or the use of small quantities of water in pharmacies to compound individually prescribed medicines.

1.4 The document can be used in whole or in part, as appropriate, to the section and application under consideration.

1.5 In addition to this document, the “Further reading” section at the end of this document includes publications that can serve as additional background material when planning, installing and operating systems intended to provide WPU.

1.6 This document is supplementary to the WHO good manufacturing practices for active pharmaceutical ingredients (2), and the WHO good manufacturing practices for pharmaceutical products: main principles (3).