Background
I was recently asked during a training event if particulate testing was a requirement for Water for Injection (WFI). My response was that it was not a requirement outlined in any major monograph for WFI, but ultimately, it is the responsibility of the end user to prove the water quality is suitable for the application.
That being said, it is a requirement of many of the major pharmacopeia that pharmaceutical waters be clear and colorless, or in the case of the Brazilian Pharmacopeia, tasteless, as well.
Since these properties for pharmaceutical waters are outlined in many international pharmacopeia’s monographs, they are technically legal requirements and as such, many companies have adopted specifications for pharmaceutical waters that include tests for color, odor, and appearance (i.e. COA tests). However, testing requirements to ensure compliance with these mandates – including procedures and frequencies – are subjective. Most COA testing performed on pharmaceutical waters is based on a simple examination at the time the sample is taken, or in the laboratory when other offline testing is performed.
Critical Quality Attributes
There are several critical quality attributes (CQAs) for pharmaceutical waters such as conductivity, total organic carbon (TOC), total viable bacteria, and endotoxin. These CQAs have defined specification limits specifically outlined in the monographs or as referenced in other test chapters. Conversely, requirements for physical properties such as color or clarity, without defined test procedures or limits, allows for different interpretations of the requirement. There are certainly many companies that are not or have never tested for color, odor, and appearance – citing the criticality of the physical properties, but not the physical appearance.
Organoleptic Tests
Organoleptic testing involves subjective testing using the sensory evaluation. It has been used in the food, wine, and drinking water industries for product evaluations. By their very name, high purity waters should contain a minimal amount of impurities, so it should always be a clear and odorless liquid. The clarity of pharmaceutical waters would be affected by the presence of suspended solids, the presence of which would be minimized by treatment techniques such as reverse osmosis (RO) or distillation. Taste and odor would impact impurities such as organic acids, which would also be removed during the treatment process. Odors that have been observed in pharmaceutical waters include the presence of ozone via improperly removal for continuously ozonated storage tanks, and amines present as the result of decomposition of anion exchange resins especially for systems operated at elevated temperatures. For these examples, tests for CQAs may yield results in specification, but organoleptic testing would fail.
By their very name, high purity waters should contain a minimal amount of impurities, so it should always be a clear and odorless liquid.
Testing Requirements
The monographs for pharmaceutical waters list the minimum quality requirements that should be monitored or periodically tested. Additional testing may be required depending on the product and application. Organoleptic testing is technically required for compendial waters to ensure compliance with the monographs, but no specific testing or specifications exist for color, clarity, odor, or taste. Our suggestion is a documented visual inspection of grab samples as a baseline approach. Certainly, additional tests such as turbidity could be used as well.
Our suggestion is a documented visual inspection of grab samples as a baseline approach.
In addition, non-ionic particulates could certainly be present undetected by traditional conductivity or TOC tests. A risk assessment should be performed, especially for parenteral products, to determine the potential risk of particulates in product waters. Additional testing, beyond organoleptic testing could certainly be required for WFI applications.