Top 3 Water Sanitization Methods For Sterile Product Processing
Why is environmental monitoring of water essential for sterile products?
Microbes in the water can easily contaminate sterile products during manufacturing. Thus, knowledge of the microbiology and biofilm formation risks within a water system is critical to monitor and control the microbial exposure of parenteral products, medical devices, and other healthcare products during manufacturing. Indeed, many biocontrol sanitization methods for sterile product manufacturing, sterile product processing, and later-stage sterile product development require knowledge of water purity and microbes in the surrounding environment.
What are the top three ways to sanitize water for sterile product processing?
Water system microbial control depends on appropriate thermal or (photo-)chemical sanitization. The top three water biocontrol sanitization methods are described below.
#1: Thermal Biocontrol Sanitization Method
Thermal sanitization systems use a combination of periodic (or continuously) circulating hot water and steam. Water temperatures for thermal sanitization vary between 65°C –80°C. Though water temperatures range, the coldest temperature reached in a thermal sanitization system should be 65°C. Many stainless-steel distribution systems successfully maintain sanitation using thermal systems with uniform temperature control and water distribution. Thermal sanitization systems are compatible with sterile product processes that use higher temperatures. Frequent thermal sanitization eliminates the need to implement other sanitization methods. Thermal sanitization systems are often capped at a temperature of 80°C, as temperatures above 80°C do not provide additional biofilm reduction and do not add to the microbial control of the water system. Further, hot water circulation at temperatures above 100°C is less effective and sometimes detrimental for two primary reasons: the need for condensate elimination and unnecessary stress on processing and water circulation equipment. Condensate elimination is another process that must be regulated to prevent condensate contamination. Poor condensate management could lead to biofilm formation issues. Undue stress on system material and deform filters can lead to increased maintenance costs and adverse impacts on sanitization instrumentation.
Other than incompatibility with heat-sensitive processes, thermal sanitization methods have an additional limitation. They are not effective at getting rid of established biofilms in water systems. Indeed, while thermal methods are excellent at continuously inhibiting biofilm growth or killing the microorganisms within developing biofilms, they cannot eliminate established biofilms. Also, thermal methods cannot inhibit biofilm re-development if sanitization processes aren’t run consistently enough. For example, killed biofilms can become nutrient sources for biofilm regrowth after the sanitizing conditions are halted. Thus, infrequent thermal sanitizations should be paired with chemical sanitization to prevent biofilm regrowth.
#2: Chemical Biocontrol Sanitization Method
Chemical sanitization methods are compatible with a wider variety of product processing materials, as these methods do not have thermal limitations. Oxidizing agents such as ozone, hydrogen peroxide, peracetic acid, or mixes of these agents are used to support water sanitization. Halogenated compounds also sanitize but are difficult to flush from the water system. Using chemical agents runs the risk that biofilms won’t be completely inactivated. Indeed, it is hard for chemical agents to carry to all crevices and cracks in hard-to-reach areas, such as gasketed fittings. Oxidizing agents destroy bacteria and biofilms with peroxides that form reactive free radicals. Each oxidizing agent has a different free radical half-life. A shorter half-life means that free radicals are only available to bind bacteria and biofilms for less time. Ozone, in particular, must be continuously added to the sanitization process (if used) due to its short half-life. Due to the reactivity of chemical oxidizing agents (such as ozone), water system components must be made from oxidation-resistant materials. Oxidizing agents are often continuously used in holding tanks and intermittently released within distribution loops for sanitization protocols.
Microbes in a well-developed biofilm may be resistant to lethal oxidizing chemicals. The thinner and less developed the biofilm, the more effective the oxidizing agent will be at destroying the biofilm. Similar to thermal sanitization, optimal microbial control is achieved by using oxidizing chemicals at a frequency that prevents biofilm growth between treatments.
#3: Ultraviolet (UV) Biocontrol Sanitization Method
UV light at a 254 nanometers (nm) wavelength can sanitize the water circulating in the water system. However, UV sanitization devices (known as in-line UV devices) must be appropriately sized for the water flow. UV devices inactivate most but not all microorganisms that flow through sterile product development or manufacturing devices. Thus, UV devices cannot directly control any existing biofilms upstream or downstream of the device. For this reason, UV sanitization is often paired with thermal or chemical sanitization techniques. UV light sanitization can significantly lengthen the interval between water system re-sanitizations, especially for thermal systems. UV sanitization devices are often found in household fish tanks to improve water quality by killing germs, parasites, and algae.
How are water sanitizations validated?
Sanitization validations confirm that a water system for sterile product development can maintain acceptable levels of microbial contamination (sterility). Thermal methods are validated using a heat distribution study to confirm that sanitization temperatures are achieved throughout the entire water system. Due to poor thermal conduction, consistent heating of some areas may be an issue. Some areas of issue are point valves, sampling ports, instrument side branches, fittings, couplings, and adapters. Chemical sanitization methods are validated by proving that water systems are dosed with the appropriate concentration of chemicals and that these chemicals flow throughout the entire system and all point valves. Any residues from chemical usage in the water system must also be tested along with any degradants. Water sampling for microbial monitoring supports validating the frequency thermal, chemical, and UV sanitization techniques must be used. Successful sanitization routines will prevent water from reaching “Alert and Action” microbial contamination levels during sterile product development and manufacturing.
Summary
Overall, microbes in the water can easily contaminate products during sterile product development and manufacturing. Thus, knowledge of the microbiology and biofilm formation risks within a water system is critical to monitor and control the microbial exposure of parenteral products, medical devices, and other healthcare products during manufacturing. Water system microbial control is dependent upon appropriate thermal or (photo-)chemical sanitization. The top three water sanitization methods are 1) thermal sanitization (hot water and steam), 2) chemical sanitization, and 3) ultraviolet (UV) sanitization. Ensure you choose a contract testing organization that can support you with appropriate environmental monitoring and microbiology testing for your sterile product processing needs.
Ethide Labs is a contract testing organization specializing in Microbiology Testing. Ethide Labs also offers Sterility Testing, Bioburden Testing, EO Residual Testing, Bacterial Endotoxin Testing, Cytotoxicity Testing, Environmental Monitoring & Package Integrity Testing services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
United States Pharmacopeial Convention. <1231> Water For Pharmaceutical Purposes. Rockville, MD, USA. 2021. (USPC <1231>).
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
