Header Artwork
Header Artwork


Water Systems and Regulatory Compliance: Is Your Water System Audit Ready?

Water, why is it so important? Water is perhaps the most widely used raw material in the MedTech industry. We have heard and read this many times and few people will argue this fact. Water is used in many different processes: as an active pharmaceutical ingredient (API), as a solvent for cleaning processes in medical devices, as a rinse in tissue manufacturing, and for reagent formulation in laboratory use—just to name a few. Yet water systems are often overlooked as a source of contamination in both viable and non-viable categories. As an input or medium for so many applications, water quality should be a focus of every risk management system.  In the pharmaceutical industry, water requirements are fairly straightforward.  The United States Pharmacopeia (USP) provides prescriptive direction regarding the grade, or quality, of water required for the intended use. However, in the medical device industry the minimal quality of processing water is vastly a gray area. With that said, water quality does not have to be complicated. Like any qualified process, ask yourself, “Is the produced water suitable for its intended use?” and, “Is your water system audit ready?”


The onus of proper selection criteria for water quality is the responsibility of the manufacturer with the expectation that an appropriate water quality, or water grade, for the process or product will be produced. Poor water quality or residual impurities in the water have the potential of adversely impacting the product, process, and even patient health.  When selecting water quality for a given process it can be accurately stated that: the level of acceptable impurities is determined by the potential of that impurity to impact the product, process, or patient health negatively. Understanding the potential impact of impurities is crucial in water system design, validation, and process control.


Regarding water impurities, if it’s not a hydrogen or hydroxide (hydroxyl group) it is considered an impurity. Water is an extremely aggressive solvent and often referred to as the “universal solvent.” Given time, water will dissolve almost any substance to which it is exposed. Therefore, even potable or drinking water from a trusted municipal source, will contain a high level of impurities absorbed from the environment. Water contaminants are commonly categorized into five major groups:


  1. Suspended particulates— undissolved solids which can be visually observed
  2. Ionic impurities—the soluble solids categorized as total dissolved solids (TDS), such as salts, metals, and other anions and cations; measured as conductivity, or the ion-facilitated electron flow through the water
  3. Microbiological impurities—bacteria, fungi, endotoxins, etc.
  4. Organic impurities—encompassing organic compounds and commonly tested as total organic carbons (TOC)
  5. Dissolved gases—which are typically atmospheric gases such as nitrogen, oxygen and carbon dioxide


As mentioned earlier, the level of acceptable impurities is determined by the potential of the impurity to impact the process, product, or patient health negatively. Determining the acceptable water quality for a process can be broken down into a three-part process which includes:


  1. Define the designated use—identifying how the water will be used and what impurities should be removed
  2. Identify water quality measurements—such as the levels of microbes, TOC, or conductivity, and determining acceptable levels required to meet the designated or intended use of the water.
  3. Establishing an anti-degradation strategy—to maintain the performance and longevity of the system. The anti-degradation strategy should include proper system design, operation, and process controls to minimize biofilm formation and system fouling


Once the acceptance criteria for the water system has been identified the system can be designed, built, and validated. The regulatory expectation is that validating a water system follows the traditional verification and validation model.  An installation qualification verifies that the system equipment and distribution loop has been installed to the manufacturer’s specification. The operational qualification verifies that the system is working as intended, including meeting flow rates, pressures, and accommodating peak demands. The final step in the validation process is the performance qualification which validates that the system is capable of continuously producing the required water specification to meet the user requirements. Once validated, the water system should be properly maintained, controlled, and monitored to ensure that the system remains in the validated state.


The risk of an improperly validated, or more importantly non-validated, water system has a significant potential of impacting clinical outcomes. Ultimately, it is the user’s responsibility to ensure that such water systems, even if producing adequate quality water and controlled exactly as intended, are properly designed, validated, monitored, and maintained according to their intended use. So again, the question, “Is your water system audit ready?


Contact your Nelson Labs sales representative if you are interested in more information about this topic or you would like a specific consultation for your facility or process.




Industry related regulatory requirements and guidance can be found in the following documents:

USP <1231> Water for Pharmaceutical Purposes

FDA, Guide to Inspections of High Purity Water Systems

AAMI TIR34:2014, Water for Reprocessing of Medical Devices

21 CFR Part 210, cGMP in Manufacturing, Processing, Packaging, or Holding of Drugs; General (210.3 Definitions)

21 CFR Part 211, cGMP for Finished Pharmaceuticals (211.65a)

21 CFR Part 820, cGMP for Medical Devices (820.3 Definitions)