Types of Pharmaceutical waters

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.

1. Purified water

2. Water for injection (WFI).

3. Pure steam

4. Water for hemodialysis.

5.  Sterile purified water. 

6. Sterile water for Injection 

7. Sterile water for irrigation

8. Sterile water for inhalation. 

9. Bacteriostatic water

Purified water. 

WHAT IS PURIFIED WATER USED FOR IN THE PHARMACEUTICAL INDUSTRY?

PHARMACEUTICAL INGREDIENTS

Water may be a required ingredient for a particular kind of medication. As ordinary water – and even drinking water – is full of trace contaminants and impurities, this will not be suitable as a pharmaceutical ingredient. Instead, a pharmaceutical water system will need to provide purified water for this application.

RECONSTITUTION

In pharmaceuticals, reconstitution simply means adding a solvent to a medication or ingredient that is in powdered form. This dissolves the medication or the ingredient so that it is suspended in a solution. The solution may either be used as a medication itself or as an ingredient in further formulation and development.

SYNTHESIS

In chemistry, and in the pharma industry in particular, synthesis is essentially the combination of two separate substances in order to create something wholly new. While this may not always require the addition of water as one of the ingredients, this water will still usually need to be present in the reaction. Impurities in water can cause significant problems during synthesis, and this is why a pharmaceutical water system needs to eliminate all such impurities as far as possible.

CLEANING

Pharmaceutical equipment will need to be cleaned before and between deployments. While cleaning will get rid of many of the potential contaminants in the process, it can add contaminants of its own in the form of tiny impurities — many of which may not be visible to the human eye. A purified water system provides the pharmaceutical industry with a reliable source of water that is ‘clean’ in a chemical sense, ready for washing and preparation. Some ingredients may also need to be cleaned, and the same high levels of care and attention will need to be applied in this process too.

TESTING AND ANALYSIS

Testing and analysis occurs at all stages of the pharmaceutical production process and is critical in gaining a better understanding of the efficacy of a medication, as well as any contraindications or side effects. The introduction of outside elements, such as impurities, can severely skew the analysis, so access to purified water is critical for analysts and development teams.

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.

Comparison of Purified water and Water for Injection Quality Parameters 

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. 

his 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).