Understanding USP Water for Pharmaceutical Use

Manufacturing of pharmaceutical products, medical devices, biologics, cell- and tissue-based products, and many other medical products requires significant volumes of water. Water is more complicated than what most people think. The two major categories are bulk water (i.e., produced on-site where used from an internal water system) and packaged water (i.e., produced elsewhere, packaged, sterilized to preserve microbial quality throughout the packaged shelf life, and purchased). Regardless of whether its bulk water or packaged water, the type of water is then determined by the testing performed, as defined by United States Pharmacopeia (USP) <1231> (1).

Water types

The following definitions can help navigate the complexities of the different types of water and provide a better understanding of their appropriate usages.

Purified water. Purified water is most commonly used as a diluent in the production of non-sterile products for injection, infusion or implantation, cleaning equipment, and cleaning non-sterile product-contact components. Purified water systems must be validated to consistently produce and distribute water of acceptable chemical and microbiological quality. However, they may be susceptible to biofilms, undesirable levels of viable microorganisms, or endotoxins, which means frequent sanitization and monitoring to ensure appropriate quality at the points of use.

Water for injection (WFI).  WFI is most often used as an excipient in the production of sterile products and other preparations when endotoxin content must be controlled. Examples are pharmaceutical applications such as cleaning of certain equipment and sterile product-contact components. WFI must meet all the same chemical requirements of purified water with added bacterial endotoxin specifications, because endotoxins are produced by microorganisms that are prone to inhabit water. As with a water system producing purified water, WFI systems also must be validated to reliably and consistently produce and distribute water of acceptable chemical and microbiological quality.

Pure steam. Pure steam is intended for use in steam-sterilizing porous loads and equipment and in other processes, such as cleaning, where condensate would directly contact official articles, containers for these articles, process surfaces that would in turn contact these articles, or materials which are used in analyzing such articles. Pure steam is prepared from suitably pretreated source water, analogous to the pretreatment used for purified water or WFI, vaporized with a suitable mist elimination, and distributed under pressure. 

Water for hemodialysis.  This type of water is specifically for hemodialysis applications and primarily for the dilution of hemodialysis concentrate solutions. Water for hemodialysis is typically produced and used on site as bulk water. This water contains no added antimicrobials and is not intended for injection.

Sterile purified water. This water has been packaged and rendered sterile. It is used for preparation of sterile products or in analytical applications requiring purified water when access to a validated system is not practical and only a small quantity is needed. It is also used when bulk packaged purified water is not suitably microbiologically controlled.

Sterile water for injection. This water has been packaged and rendered sterile. This water is for the processing of sterile products intended to be used intravenously. Additionally, it is used for other applications where bulk WFI or purified water is indicated but access to a validated water system is either not practical or only a relatively small quantity is needed. Sterile WFI is typically packaged in single-dose containers that are typically less than 1 L in size.

Sterile water for irrigation. This water has been packaged and rendered sterile. This water is commonly used when sterile water is required, but when the application does not have particulate matter specifications. Sterile water for irrigation is often packaged in containers that are typically greater than 1 L in size.

Sterile water for inhalation. This water has been packaged and rendered sterile. This water is usually intended for use with inhalators and in preparation of inhalation solutions. It carries a less stringent specification for bacterial endotoxins than sterile WFI and, therefore, is not suitable for parenteral applications.

Bacteriostatic water for injection. This water is sterile WFI to which one or more suitable antimicrobial preservatives have been added. This water is typically intended for use as a diluent in the preparation of sterile products, mostly for multi-dose products that require repeated content withdrawals, such as liquid pharmaceuticals. It may be packaged in single-dose or multiple-dose containers, usually less than 30 mL.

With nine different types of water, each with specific testing requirements and applications, it is crucial to understand how they can impact products. Using a less stringent type of water for a product based on its intended use could be a costly mistake. Similarly, using a more stringent type of water, when not required, could result in increased costs. Add in the increased scrutiny of the ever-changing regulatory landscape, it becomes even more critical to have a complete understanding of the water a process requires.

Reference

1.  USP <1231> Water for Pharmaceutical Purposes. (Rockville, MD, March 8, 2017).

About the author

Aaron Schieving is Corporate Director of Sales & Marketing for Texas-based Lifecycle Biotechnologies, parent company to Chata Biosystems, a chemical and reagent manufacturer, aschieving@lifecyclebio.com.