Water Sampling Methods For Environmental Monitoring Of Parenteral Products
Why is water sampling necessary for parenteral products?
Microbes in the water can easily contaminate parenteral products during manufacturing. Thus, water sampling and testing are critical to the ongoing environmental monitoring and control for parenteral product manufacturing. If water samples are improperly collected, a sample could yield a false-positive or false-negative result. These results could lead to inaction (when corrective measures are needed) or to unnecessary remediation when none is necessary. Therefore, proper water sampling plan creation, water sample collection, and test result interpretation are essential to water quality control and environmental monitoring excellence.
When is water sampling performed?
Water samples must be obtained from locations that are representative of the issue being monitored. Generally, water testing data are used for process control (PC) of the water purification and distribution system or quality control (QC) of the water drawn from the purification system for product manufacturing or assembly cleaning. As an example of quality control, water samples might be collected from areas in the pipeline prone to microbial contamination to ensure that pipelines are continuously free of contaminants. For process control, water samples might be collected from multiple locations in the water purification and distribution system to troubleshoot an unexpected source of contamination.
How is water sampling performed?
Water sampling for process control sampling and quality control sampling differ. The water sampling process for both PC and QC sampling is further detailed below.
Process control (PC) sampling
PC sampling reflects the water quality within the distribution system, from the purification system, or between water purification steps. When performing PC sampling, efforts must be made to avoid contaminating the water drawn from the system. Avoiding water contamination during sampling keeps water sampling test results accurate. Thus, samples are taken at strategically located sampling ports and points-of-use areas. Sampling ports for PC sampling should have valves with a vigorous pre-sampling flushing design. The pre-sampling flushing removes any biofilm structures growing on valve surfaces before the sample is collected. Removal of biofilm from the valve surface avoids biasing the microbial count of the water in the system behind the valve. As a valve flush standard, an open valve flush at eight feet of water per second for at least thirty seconds will remove any fragile biofilm structures. For testing, sterile hoses, gaskets, or other connectors are used for water sampling to prevent sample contamination. When water PC data is accurately collected, this information indicates how well a purification system maintains water quality and if system maintenance is required to restore water purity.
Quality control (QC) sampling
QC sampling reflects the quality of the water being used for a process. QC samples are collected at the point of use, i.e., where the water is delivered for use, not where the water leaves the water purification system. QC samples must come from the same delivery path and components employed for a water transfer during water use for the manufacturing or cleaning process under evaluation. Examples of delivery path components include valves, hoses, heat exchangers, flow totalizers, and hard-piped connections. Additionally, QC sampling must use the same pre-use outlet, delivery path flushing procedure, hose sanitation practices, and outlet fitting processes used during actual water use. Essentially, QC samples must mimic the quality of water used in a process and accumulate the same chemical and microbial contaminant levels as would occur during actual use. Where the water transfer conduit for a permanent connection is designed or treated to remove all contaminating influences before water transfer through that conduit, PC sampling locations within the distribution system reflect the quality of the water used for QC purposes.
Which water sources are sampled routinely?
Four categories of water sources are consistently sampled to prevent or troubleshoot contamination of parenteral products.
#1: Source water sampling
Source water is where water for purification is sourced. Typically, source water comes from a local water authority and meets local drinking water regulations. The quality of source water when it reaches the manufacturing or pharmaceutical user is dependent on its distance from the input source, duration of travel within city piping, and the condition of the piping in the potable water distribution grid. Any of the three factors listed above can drastically impact the chemical and microbial content of the water. Chemical content includes heavy metals, salts, household cleaners, and other household or industrial waste products. It is helpful to verify drinking water criteria are met before the water enters the pretreatment system. Drinking water test results can be provided by the water authority or by periodic retesting of drinking water by the user. Source water may be periodically assessed for the microbial count, the absence of coliforms, bacterial endotoxin levels, conductivity, pH, hardness, lead, chlorine, silica, and silt density index. These data are useful for operational adjustments to water purification processes and for feedback to the potable water provider.
#2: Pretreatment and purification system sampling
The pretreatment and purification system is the first step in the water purification process for source water. The sampling of pretreatment and purification systems is used for water process control. A risk analysis of the unit’s operation determines the sampling frequency and location within pretreatment and purification systems. Any quality deviations early in the water purification process can affect unit operational efficiency. However, these deviations rarely impact the finished water quality. Thus, sampling of water at early purification stages is less frequent than at other purification stages.
#3: Purified water distribution system sampling
Purified water distribution system sampling ensures PC compliance with the purified water’s chemical and microbiological requirements. Often, less sampling is needed for proof of chemical requirements compared to microbiological requirements. However, in cases where the chemical quality can change dramatically (such as with the exhaustion of deionization beds), chemical attributes will need to be monitored with the same frequency as microbe content. For microbial sampling, all sample ports in a distribution system are tested routinely, including those infrequently used by manufacturing. There is no standard for the sampling frequency of purified water system outlets. As a result, testing frequency is a matter of risk tolerance for PC and QC consistency. Typical outlet sampling frequencies vary from daily to monthly. With less frequent sampling, more products and processes are impacted if an unfavorable test result does occur.
#4: Water-for-Injection system sampling
The regulatory expectations for water-for-injection distribution systems are more extensive than the criteria for purified water systems because the microbial control must be more stringent to prevent bacterial endotoxin contamination. Indeed, water sampling for microbial and bacterial endotoxin testing occurs daily in injection distribution systems. Further, each outlet is sampled periodically, based on a risk assessment, to characterize the quality of the water.
How is non-routine water sampling performed?
Non-routine sampling is performed on water systems with episodic contamination events or when routine sampling plans are insufficient to capture the needed data. Examples of non-routine sampling situations include change control purposes such as evaluating the effects of changes to sampling, data for long-term informational purposes, or investigations for deviations from normal sampling results and criteria.
Summary
Overall, microbes in the water can easily contaminate parenteral products during manufacturing. Thus, water sampling and testing are critical to the ongoing environmental monitoring and control for parenteral product manufacturing. If water samples are improperly collected, samples could yield a false-positive or false-negative result. Generally, water testing data are used for process control (PC) of the water purification and distribution system or for quality control (QC) of the water being drawn from the system for product manufacturing or assembly cleaning. Four categories of water sources are consistently sampled to prevent or troubleshoot contamination of parenteral products. These four water sources are source water sampling, pretreatment and purification system sampling, purified water distribution system sampling, and injection distribution system sampling. All in all, ensure you choose a contract testing organization that can provide appropriate environmental monitoring and microbiology testing for your product needs.
MycoScience is a contract manufacturing organization specializing in sterile syringe and vial filling. MycoScience also offers Preservative Efficacy Testing, Sterilization Validations, Bioburden Testing, Cleaning Validations, Microbial Aerosol Challenge Testing, Accelerated Aging, Microbiology Testing, Cytotoxicity Testing, Bacterial Endotoxin Testing, EO Residual Testing, Package Integrity Testing & Environmental Monitoring services medical devices and allied industries. MycoScience is an ISO 13485 certified facility.
References
United States Pharmacopeial Convention. <1231> Water For Pharmaceutical Purposes. Rockville, MD, USA. 2021. (USPC <1231>).
