What Is Vapor Phase Sterilization?
What is sterilization, and why is it essential for sterile products?
Sterilization keeps patients safe from toxins and microbial illnesses when therapies or devices are consumed or used. Sterilization is any process that removes, kills, or deactivates all forms of life. Under the strictest definition of sterility, an item or product is sterile when there is the complete absence of viable microorganisms (bacteria, yeasts, viruses, and molds). For regulatory purposes, sterility is defined by acceptance criteria based on calculated contamination probability. An acceptable level of contamination risk for most items is the probability of a single contaminated product out of a million manufactured products. However, sterility criteria may be more stringent or lax depending upon the intended use of the medical device or product.
Commonly, sterile products undergo sterilization processes that utilize chemicals, heat, radiation, or filters. Sterilization kills any microorganisms products collect during manufacturing. A less common version of sterilization is vapor phase sterilization.
What is vapor phase sterilization?
Vapor is an agent or molecule that is suspended in the air. Vapor phase sterilization sterilizes products through exposure to sporicidal agents suspended in the air. Traditional vapor phase sterilization agents are hydrogen peroxide (H2O2), peracetic acid (CH3CO3CH), formaldehyde (CH2O), and glutaraldehyde [CH2(CH2CHO)2]. Sterilizing gases and liquids differ from vapor phase agents, as vapor phase agents expose products to multiple phases (liquid, gas, etc.) during sterilization.
What products or medical devices can undergo vapor phase sterilization?
Vapor sterilization works well for heat-sensitive materials and for the sterilization of surfaces.
How is vapor phase sterilization performed?
At room temperature, vapor phase agents (liquids or solids) vaporize and can be utilized for sterilization within a sealed chamber or vessel. Vapor sterilization must have a correct sterilant concentration, chamber temperature, and relative humidity for the items undergoing sterilization. Typically, the sterilant concentration (amount) will be determined from its injection quantities into the sterilization chamber. Vapor phase agents are most often introduced as an aqueous solution. For example, a standard vapor sterilization process involves adding items into the sterilization chamber and then adding heat and humidity. Next, the sterilant agent is introduced (sometimes through an atomizer), and the products are marinated in the vaporized sterilant for a set time. And finally, allowing the vapor to be removed from the system or evaporate before opening the chamber and removing the newly sterile items. If introduced as an aqueous solution, water moisture is introduced along with the sterilant. This added moisture is factored into humidity and condensation considerations for the sterilization process. Out of all vapor phase agents, hydrogen peroxide and peracetic acid are widely used and the most established for sterilization.
Hydrogen Peroxide Vapor Phase Sterilization
Hydrogen peroxide has a long history of being a liquid sterilant in healthcare and other industries. Hydrogen peroxide can be added into a sterilization chamber through multiple approaches. These approaches are continuous administration, intermittent administration, or injecting the entire dose of hydrogen peroxide all at once. Some vapor phase sterilization protocols have a drying step before adding the hydrogen peroxide. This drying step allows the hydrogen peroxide concentration within the sterilization chamber to increase without additional condensation. Hydrogen peroxide can also be introduced to a chamber as a liquid and exposed to targeted heating to create the vapor phase. Like gaseous sterilization methods, the sterilization chamber is aerated, and the sterilant gas is allowed to dissipate before the sterilized medical devices, products, and other items are removed.
Peracetic Acid Vapor Phase Sterilization
Peracetic acid may be used alone or mixed with hydrogen peroxide to sterilize medical products and devices. Peracetic acid is a liquid sterilant. An atomizer is used to distribute peracetic acid for vapor phase sterilization. The atomizer allows both liquid and vapor forms of peracetic acid to be present during sterilization. After peracetic acid exposure, evaporation is used to remove all peracetic acid from the system.
What are some difficulties with vapor sterilization?
Vapor phase sterilization can be challenging to validate as relative humidity, sterilant concentration, and condensation rate varies throughout the sterilization process. These variations cause localized differences in sterile conditions within a sterilization chamber. Thus, some products or product areas may not experience the same microbial lethality as other products or product parts. Further, there is no standardized biological indicator for vapor systems as it is a liquid and a gas combined sterilization system. D-values (which determine the lethality of a sterilization process) can be tricky to calculate for vapor sterilization systems because gas-phase conditions, surface conditions, and microbial lethality do not have known correlations. D-values can only be calculated under well-defined, system-to-system specific conditions.
How do you validate a vapor sterilization process?
Since vapor sterilization has multiple phases (liquid and gas) that vary over time, no standardized biological indicators or D-values can be used across the board for vapor phase sterilization validations. An empirical approach is taken with vapor sterilization processes since D-values are inconsistent. D-value inconsistencies occur because the lethality of a sterilant is different in the gas vs. the liquid phase. Generally, liquid phase kill rates are greater than gaseous kill rates. Thus, sterilization process parameters must be modified until a complete kill of all microbes is achieved, no matter the location of the items within the sterilization chamber. The vapor sterilization parameters for a total kill are the minimum conditions needed to kill a particular amount of bioburden. In some cases, vapor sterilization may be validated using a half-cycle or bracketing approach, like liquid chemical sterilization. Please see our article on liquid phase sterilization for more details on half-cycle and bracketing approaches. A bracketing approach is better for defining maximum and minimum operating ranges for critical sterilization parameters than the half-cycle method.
Sterilization validation activities that may need adaptation for intermittent or continuous vapor sterilization processes:
- Equipment qualification— The equipment qualification for vapor sterilization confirms equipment installation and operation.
- Empty chamber parameter distribution— Humidity measurements, temperature measurements, and chemical indicators provide information on vapor sterilant distribution. Biological indicators are not needed for empty chamber assessments.
- Component mapping— If vapor is used for outer surface sterilization, mapping of load items is not needed. If a product requires internal surfaces to be sterilized, a component mapping should be performed, and biological indicators placed in areas that are difficult to sterilize to confirm vapor phase lethality.
- Load mapping— For this activity, load size (item number) and patterns used to load items are assessed for their microbial lethality under the vapor sterilant conditions.
- Biological indicators— Selection of the biological indicators, their concentration, and resistance to sterilization should be based on the bioburden accumulated by the products during manufacture. As mentioned earlier, there are no biological indicator standards for vapor sterilization.
- Process confirmation and microbiological challenge— Final process validation requires confirming the vapor sterilization process can repeatedly inactivate biological indicators. In some cases, a microbial challenge of item surfaces may be used instead of manufacturer- or lab-prepared biological indicators. Chemical and physical measurements must also repeatedly fall within acceptance criteria for the vapor sterilization process.
Essential practices required to maintain validated status for vapor phase sterilization include:
- Regular calibration
- Physical measurements
- Biological indicator usage and regulation
- Physical or chemical integrators and indicator use and regulation
- Ongoing process control
- Ongoing change control
- Preventive maintenance
- Periodic reassessments
- Training of personnel
Summary
Overall, medical devices, products, and therapies must be sterile. Sterilization is any process that removes, kills, or deactivates microbes. Vapor phase sterilization inactivates microbes through exposure to sporicidal agents suspended in the air. Typical vapor phase sterilization agents are hydrogen peroxide, peracetic acid, formaldehyde, and glutaraldehyde. Sterilizing gases and liquids differ from vapor phase agents, as vapor phase agents expose products to multiple phases (liquid, gas, etc.) during sterilization vs. a single phase. Out of all vapor phase agents, hydrogen peroxide and peracetic acid are widely used and the most established for sterilization. Vapor sterilization works well for heat-sensitive materials and the sterilization of surfaces. All in all, ensure you choose a contract testing organization that can provide appropriate sterility testing for your product needs.
Ethide Labs is a contract testing organization specializing in Sterilization Validations and Sterility Testing. Ethide Labs also offers Microbiology 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
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
United States Pharmacopeial Convention. <1229.11> Vapor Phase Sterilization. Rockville, MD, USA. 2021. (USPC <1229.11>).
