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WATER FOR INJECTION AND COMPENDIAL WATERS IN PHARMACOPOEIAS

Only few types of pharmaceutical water have USP designation and are subjects of official monographs in the current US Pharmacopeia. However, the same document says that “Although there are no absolute microbial standards for water (other than water intended to be sterile), the cGMP regulations require that appropriate specifications be established and monitored”. “(…) i.e. water used to formulate a product should contain no organism capable of growing in the product. (…)”. This is the reason for which in Bram-Cor every water treatment system is really customized and oriented to a specific pharmaceutical plant, line and product.

ISPE document (ISPE BASELINE© GUIDE, Water and steam Systems) explains what water can be used in the development, in manufacturing and in the preparation of drugs. These waters are divided into two categories:

1. COMPENDIAL WATER
2. NON-COMPENDIAL WATER

A. PHARMACEUTICAL COMPENDIAL WATERS

Compendial waters meet the USP, EP (European Pharmacopoeia) and JP (Japan Pharmacopoeia) requirements but, in according with FDA, the ISPE document notes that: “(…) the specifications outlined in the monographs (USP, EP end JP) are the minimum requirements for Water for Injection and compendial waters. Additional specifications may be added or combined based on process requirements”.

Compendial waters in ISPE examples are:

1.  Purified Water (PW), as defined by USP, EP, JP, ChP and IP monographs.

Purified Water is classified for pharmaceutical use as an excipient in the production of non-parenteral preparations and, in specific, for pharmaceutical preparations/tests and assays, for which water is indicated, unless otherwise specified (see related USP, EP and JP pharmacopeia for reference). Drinking water is the minimal source of feed water to produce PW, through deionization, distillation, ion exchange, reverse osmosis, filtration or other appropriate procedures. PW is also a starting material in the WFI and pure steam preparations.

Purified Water (PW) table - Differences in Pharmacopoeias
Purified Water (PW) table – Differences in Pharmacopoeias (data can change without notice)

Sterile Purified Water, as defined by USP, is PW packaged and rendered sterile; it is used in applications requiring Purified Water, where access to a validated Purified Water System is not serviceable (small q.ty needed, for example).

2. Water for Injection (WFI), as defined by USP, EP, JP, ChP and IP monographs.

Water for Injection is classified for pharmaceutical purposes as an excipient in the production of parenteral preparations and in other pharmaceutical preparations where the endotoxin content must be verified (see related USP, EP and JP pharmacopeia for reference). Deionized water (that may be pre-treated for subsequent distillation or appropriate process) is the minimal source of feed water to produce WFI. In addition to the PW specifications, WFI adds the test for Bacterial endotoxins and complies with all requirements (except for Labeling) for the packaged water know as “Sterile Purified Water” (see USP monograph). 

Water for Injection table - WFI Differences in Pharmacopoeias
Water for Injection (WFI) – Differences in Pharmacopoeias (data can change without notice)

Sterile Water for Injection, as defined by USP. It is WFI packaged and rendered sterile; it is used in applications requiring Water for Injection, where access to a validated WFI System is not serviceable (small q.ty needed, for example).

Bacteriostatic Water for Injection, as defined by USP. It is WFI with addition of one or more antimicrobial preservatives; it is used as a diluent in the preparation of parenteral solutions (especially for multi-dose products that allow repeated withdrawals).

Producing Water for Injection – Note on pharmacopoeias

USP 27 (2004) revised USP WFI monograph; it admits WFI from “Distillation or a purification process that is equivalent or superior to distillation in the removal of chemicals and microorganisms”. In 2008 EMEA (European Medicines Evaluation Agency, now EMA) issued a Reflection Paper to explain why the use of membrane technology was not considered acceptable for the production of WFI. From 2010 EDQM (European Directorate for the Quality of Medicines & HealthCare) works on surveys to collect industry data on “Preparation WFI grade water using Reverse Osmosis (RO)”. In 2011 EDQM (Expert Workshop) examines potential uses of the membrane systems for the WFI production and, in 2014, works to allow non-distillation technologies to be included in EP, in addition to distillation for WFI production. In recent years, documents (EMA Q&A EMA / INS / GMP / 489331 / 2016) and related issues are again examined. As a consequence (EP 9.1 publication), HPW  monograph (see below) will be deleted.

3. WFH (Water For Hemodialysis), as defined by USP monograph.

Water For Hemodialysis is primarily classified in pharmaceutical purposes for hemodialysis applications (see related USP monograph), i.e. for example in the diluition of concentrate solutions. It’s made from EPA (US Environmental Protection Agency) drinking water which has been further purified to reduce chemical and microbiological components. Note that WFH is not intended for injection.

Note that Purified Water or Water For Injection that are packaged must be sterilized to preserve their microbiological properties; so we have other packaged monographed waters, as Sterile purified water, Sterile water for injection, Bacteriostatic water for injection, and so on (see related USP monographs).

 

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