Part 2: Development of Hydrogen Peroxide Gas Systems
Development of Gas Systems
The first commercial gas systems were developed in the 1980s and sold under the AMSCO (American Sterilizer Company) “VHP” trademark for “vaporized hydrogen peroxide”. These systems were designed for the disinfection of any enclosed areas such as rooms, isolators and cabinets. They were attached to or enclosed within the area to be disinfected and controlled through a process that includes de-humidification, conditioning, disinfection (or sterilization) and aeration.
2001‐2002 Bioterrorism: VHP technology was one of the technologies used to disinfect a whole building contaminated with Bacillus anthracis (anthrax) spores during the bioterrorism events in the United States during the early 2000s.
Hospital Applications: It was not long before similar applications were used in hospitals for the environmental disinfection of rooms and areas, in particular during outbreak situations.
Over the last 10 years it has become clear that hydrogen peroxides, whether in the gas or liquid state, differ dramatically in their ability to kill microorganisms (efficacy) and their corresponding safety profiles. Example: Mycobacterium terrae
This table provides examples of the antimicrobial activity of hydrogen peroxide in both the gas and liquid forms against a microorganism known as Mycobacterium terrae. The efficacy against Mycobacteria is important to demonstrate for high level disinfection claims.
Hydrogen peroxide in the liquid phase can be effective but requires more than 5 minutes for a typical D‐value (for a 6 log reduction this would be 30 minutes). In comparison a formulated liquid hydrogen peroxide solution is effective at only 45 seconds at 22 degrees Celsius and the D-value decreases even further at 30 degrees Celsius. Note that 2% hydrogen peroxide in water is equal to about 20,000ppm. But look at hydrogen peroxide gas; at much lower concentrations, for example at 1 or 4 mg/L, it is rapidly effective.
Vacuum (Sterilization) Applications
There are essentially two types of hydrogen peroxide gas sterilization processes that have been described in Part 1: the use of hydrogen peroxide gas on its own (no plasma), and using hydrogen peroxide gas excited into a plasma. Plasma is used as part of some sterilization processes, but not for antimicrobial activity.
Plasma vs. Non Plasma Processes
Lets compare what typically happens in these processes:
The graph shows pressure on the vertical (Y) axis and time on the horizontal (X) axis. The dotted line indicates atmospheric pressure. Both processes run under low pressure (vacuum) and consist of three phases: conditioning, sterilization and aeration. In the case of a non‐plasma process, conditioning is where the load is prepared for sterilization (e.g. drying, air removal), followed by the introduction of hydrogen peroxide gas in a series of pulses (introduction, hold and removal being a single pulse) and then aeration to remove any residual gas.
The plasma process is similar, but as shown above, after the gas has been introduced and removed from the chamber, the plasma (indicated by P) is applied, and is essentially being used to get rid of any gas/liquid residual than can remain in that specific process.
These are examples of specific hydrogen peroxide gas systems that have been recently developed for medical device sterilization in healthcare facilities, with or without use of plasma.
How Gas Processes Can Vary
Each specific sterilization process will vary slightly. To date, plasma has been only used to aid in aeration or removal of hydrogen peroxide residuals. What is important to remember is that despite sounding the same, each process is different. Differences will include antimicrobial activity, load penetration (including lumen penetration) and device compatibility to name a few.
New Sterilization Applications
Concentrated Hydrogen Peroxide Gas Plasma Process (NX)
This is an example of a newer hydrogen peroxide gas and plasma system, known as the STERRAD NX. This is unique as the gas is concentrated at the start of the process (to remove the water) and then used at extremely concentrated gas conditions (up to 90% hydrogen peroxide) for sterilization in a series of two pulses.
Note for each pulse the gas is introduced, held, and then removed; only then is the plasma ‘sparked’. Overall, the plasma is not believed to play an important role in the antimicrobial activity but is important for the safety (residual removal) of this particular process.
Hydrogen Peroxide Gas Process (No Plasma)
This is an example of a non‐plasma process. The conditioning cycle is developed to aid in residual moisture removal. Sterilization proceeds in a series of 4 pulses designed to aid in load/lumen penetration by hydrogen peroxide gas and then followed by the use of vacuum to remove any hydrogen peroxide residuals.
Both the FDA and ISO require that sterilizers are designed to be effective and safe. The applicable ISO standard in this case is ISO 14937. Many other associated standards pertaining to biocompatibility and electrical safety standards are applicable in addition to other local requirements, which can apply in specific countries/regions.
Some of the important safety considerations include:
- Safety for The Patient
- No toxic substances remaining on the device (e.g., ISO 10993-17: Biological evaluation of medical devices. Part 17: Establishment of allowable limits for leachable substances)
- Safety for Devices
- Material, component and device testing
- Ongoing device testing program
- Safety for Staff
- Electrical and mechanical safety
- Gas safety levels
- Safety for the Environment
- Degrades into water and oxygen
Effectiveness Against Microorganisms
On the antimicrobial side, the first requirement is to show hydrogen peroxide gas sterilizers are effective against all known microorganisms including bacteria, bacterial spores, mycobacteria, viruses and fungi. Note that the antimicrobial activity of hydrogen peroxide gas has been well described in literature, including all these types of organisms, as well as protozoa.
Sterility Assurance Level
The next step is to show that the hydrogen peroxide gas sterilizer process is defined, and can provide an acceptable sterility assurance level (SAL) under minimal conditions. For hydrogen peroxide gas processes the key variables are the gas concentration, temperature, time and pressure. If plasma is used as part of the process, this also needs to be understood.
The FDA and clinical customers require that hydrogen peroxide gas sterilizers be shown to be safe and compatible with marketed devices. Such testing is generally conducted under both laboratory “simulated use” conditions, and in actual clinical use. Device testing includes testing that devices are sterilized when processed according to the manufacturer’s instructions for use, and also that the process is compatible with the device’s materials of construction. Common compatibility challenges include hydrogen peroxide reacting with copper and paper (cellulose). Some devices may also be pressure sensitive, and these devices may require use of a gas cap to relieve pressure during the sterilization process. There are two sources of information on device compatibility: from the instructions for use of the device, and the sterilizer manufacturer. Both should be considered.
In conclusion, hydrogen peroxide is a powerful antimicrobial that has been used for over 150 years. It is used both in liquid and gas form. In liquid form, it can be optimized for use by mixing with other defined chemicals (in formulation). In gas form it is very effective and has been developed for disinfection and sterilization applications. In gas form, hydrogen peroxide has been shown to be safe for use and very effective for disinfection or sterilization within specific processing systems.