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USP describes analytical and microbiology testing required for different types of pharmaceutical water.
Manufacturing of pharmaceuticals, medical devices, biologics, cell- and tissue-based products, and many other medical products requires significant volumes of water. The author outlined the different types of water and their most common applications in a previous article (1). These different water types are determined based on the various testing performed. The following definitions can help navigate these complexities through a deeper understanding of the analytical and microbiology testing based on the requirements set forth in the United States Pharmacopeia (USP) <1231> (2).
Total organic carbon (TOC) testing is performed as a means for screening for organic molecules introduced from source water, from purification and distribution system materials, and from biofilm growing in the system.
Conductivity testing is performed to measure the ion-facilitated electron flow through the water. Water molecules dissociate into ions as a function of pH and temperature and result in a predictable conductivity. Conductivity can be affected by the presence of carbon dioxide and inorganic dissolved solids, such as chloride, nitrate, sulfate, phosphate anions, sodium, magnesium, calcium, iron, and aluminum cations.
Bacterial endotoxins testing (BET), also referred to as pyrogen testing, is a test that uses Limulus Amebocyte Lysate, a reagent derived from the blood of the horseshoe crab (Limulus polyphemus), to detect the presence of bacterial endotoxin in the water. Bacterial endotoxin is found in the cell wall of gram negative bacteria and causes a fever in mammalian species.
Sterility testing is performed on the water to determine the presence or absence of viable microorganisms on products or portions thereof.
Microbial enumeration testing allows quantitative enumeration of mesophilic bacteria and fungi that may grow under aerobic conditions. These tests are designed primarily to determine whether the water complies with an established specification for microbiological quality.
Particulates testing is of particular concern in injections and parenteral infusions consisting of extraneous mobile undissolved particles, other than gas bubbles, unintentionally present in the solutions. Water designated for use in injectable products requires this testing to ensure the source water is not adding particulate matter into the final product that could be introduced intravenously.
Antimicrobial agents testing demonstrates the effectiveness of antimicrobial protection. Antimicrobial preservatives are toxic substances added to non-sterile dosage forms to protect them from microbiological growth or from microorganisms that are introduced inadvertently during or subsequent to the manufacturing process. In the case of sterile articles packaged in multiple-dose containers, antimicrobial preservatives are added to inhibit the growth of microorganisms that may be introduced from repeatedly withdrawing individual doses.
pH testing evaluates the negative log of the activity of the hydrogen ion in the water.
Calcium, carbon dioxide, and sulfates are all qualitative tests to determine the amounts of these substances in the water.
Having a robust understanding of each different test will provide a roadmap for how water impacts each product. 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, and it becomes crucial to have a complete understanding of the water a process requires.
The final piece is knowing which tests are required for each type of water. Table I summarizes the requirements needed to claim a particular water type.
Water types and testing variables can be a complicated process. Knowing the specifics of the water used for processing is crucial to ensure optimal patient care. Water may seem ordinary, but the impact it has on patients’ lives is proof of its tremendous need and value.
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, firstname.lastname@example.org.