Vaporized Hydrogen Peroxide VHP Sterilization Technology
Vaporized Hydrogen Peroxide VHP Sterilization Technology
vaporized hydrogen peroxide (Vaporized Hydrogen Peroxide, the abbreviation VHP) sterilization technology, is the use of hydrogen peroxide at room temperature in the gas state is more than the advantages of the liquid state spore killing ability, the generation of free hydroxyl, used to attack cell components, including lipids, proteins and DNA, a technology to achieve complete sterilization requirements. Commonly used in isolation room, isolator and other confined space sterilization. Vaporized hydrogen peroxide (VHP) sterilization dry, fast, non-toxic, no residue, good material compatibility, including many metals and plastics, suitable for room, biological safety cabinet, transfer window, animal cage exchange station, isolator and medical equipment surface sterilization. The biological purification time is short. According to the physical characteristics of the product to be treated, the biological sterilization time is 30~90min, which is effective for a wider range of microorganisms. The biological sterilization cycle does not produce toxic residues, and has little effect on other items (devices, electrical appliances, clean room wallboards, etc.) The time required for sterilization is short and easy to verify.
pharmaceutical factory mainly include disinfectant wiping method, ultraviolet lamp irradiation method, formaldehyde fumigation disinfection, chlorine dioxide gas disinfection, etc. These methods have the characteristics of poor repeatability, difficult to verify, great destruction, need to consume a lot of manpower, and will endanger the health of operators. In today's pharmaceutical industry, hydrogen peroxide has gradually replaced the traditional sterilization method, become the common method of surface or space disinfection and sterilization, hydrogen peroxide is composed of water and oxygen, both are very safe, in the sterilization effectiveness, personnel safety, material compatibility and environmental has obvious advantages.
For humans, exposure to a certain concentration level of sterilizing gas is harmful to health, and this concentration level varies with different gases. According to the data published by the Occupational Safety and Health Administration (OSHA), the safety indicators of the three disinfection technologies of formaldehyde fumigation, chlorine dioxide gas and vaporized hydrogen peroxide are compared in the table.
| Major Projects | three gas disinfection technical safety indicators (mg/L) | ||
| hydrogen peroxide | Chlorine Dioxide | Formaldehyde | |
| direct contact | skin eye irritation | severe irritation | human carcinogenic |
| PEL | 1.0 | 0.1 | 0.75 |
| STEL | - | 0.3 | 2 |
| IDLH | 75 | 5.0 | 10 |
| sterilization concentration | 150-700 | 350-1500 | 8000-10000 |
| Note: PEL,8h allowable exposure limit. STEL,15min short exposure limit. IDLH, Limits for Acute Hazards to Life and Health. | |||
hydrogen peroxide as early as 100 years ago proved to have a good bactericidal effect, can kill a variety of bacteria, fungi, viruses and bacterial spores, its 3.0% aqueous solution can be used for local disinfection of human skin and mucous membranes, more than 6.0% concentration can be used for high-level disinfection of corrosion-resistant items. The principle of its bactericidal action is mainly through oxidation, and the free radical group produced after decomposition, which destroys the protein, amino acid, enzyme and DNA of the microorganism, destroys the permeability barrier of the microorganism, and eventually leads to the death of the microorganism.
the liquid becomes a gas, it needs to be heated and vaporized. Generally, the vaporization temperature of water is 100 ℃, and the vaporization temperature of pure hydrogen peroxide is 150.2 ℃, while the vaporization temperature of 30% - 35% hydrogen peroxide solution is about 108 ℃. Vaporized hydrogen peroxide sterilization technology must use a heater, or hydrogen peroxide vapor generator, to convert liquid hydrogen peroxide into VHP through so-called "flash evaporation". This process can be effectively carried out at room temperature.
air is mainly composed of nitrogen, oxygen, water gas and a small amount of inert gas. How much water in the air can not be seen visually, but can be measured by the instrument, the amount of water in the air, generally expressed by relative humidity (RH). When the temperature drops, the water vapor in the air will form very small mist particles. The larger the water vapor, the lower the temperature. When it reaches the point of "condensation", dew will form and settle down.
the same principle, VHP with higher temperature is evenly introduced into the confined space. Generally, the VHP gas concentration maintained is 150 - 700 mg/L. When the temperature in the space is relatively low, 1 micron nano fog (also called dry fog) will be formed. Both steam and nano fog have the characteristics of extremely easy penetration through various objects, making the contaminated surface completely exposed to VHP and attached to the surface of resident microorganisms, contact with VHP at room temperature will further form micro-condensation. Theoretically, the concentration of VHP will rise rapidly after condensation (the concentration of water after condensation is 100, and the concentration of hydrogen peroxide after condensation of VHP can reach more than 70%), and various microorganisms will be rapidly killed.
study found that when the concentration of the target environment during the VHP cycle reaches its peak, a layer of invisible deposits will form on the surface of all exposed objects. Under the microscope, it is a condensed film of about 2 μm, which produces a more effective killing effect. Once the hydrogen peroxide molecule contacts the surface of the object, it immediately produces oxidation to form free radicals to attack microorganisms, achieves a high level of disinfection and sterilization, and is effective against bacteria, spores, fungi, molds and viruses.
The entire process is controlled outside the confined space through a computer and a color touch screen, and real-time feedback of the loop process. The space or equipment sterilized by VHP needs to be sealed. The handheld VHP sensor based on electrochemical principles monitors that no leakage occurs and whether the environment is After the cycle, it returns to a safe level that can be entered.
2. VHP Disinfection Technology Advantage
1, Safety
steam sterilization is used, personnel access is restricted during the entire sterilization process and can be safely recovered if sterilization fails.
2, reliable
Through the vaporized hydrogen peroxide sterilization treatment, the air and surface sterilization logarithm in the sealed barrier can reach 4 to 6, and the whole sterilization process is simple and reliable.
3, intelligent
can be integrated with building facilities, and BMS control integration, the entire disinfection process can replace the operator, reduce the operator dependence.
4. Standardization
the combination of hydrogen peroxide technology and air conditioning system can effectively avoid the problems of traditional sterilization, such as difficulty in standardization and verification.
At present, the common hydrogen peroxide disinfection methods in pharmaceutical plants mainly include vaporized hydrogen peroxide, gas-source atomized hydrogen peroxide and power-source atomized hydrogen peroxide sterilization.
| Observation Project | concentration (g/L) | consumption (ml/m & sup3;) | carrier gas means | current-equalizing mode | disinfection time (h) | temperature and humidity | Kill logarithm | Corrosivity | operators | Residue removal time (min) | Concentration in air (mg/m & sup3;) | Auxiliary Facilities |
| vaporization | 300~600 | >20 | Internal and external fans | External fan | 5-8 | 30 ℃,30% | >6.0 | obviously | 3-5 | >30 | ≥ 250 | current-sharing unit |
| gas source atomization | compound hydrogen peroxide | >20 | compressed air | compressed air | >4 | Normal temperature and humidity | >4.0 | corrosive | 3-5 | Fan | ||
| power supply atomization | 80g/L mixed with 5% ethanol | >8 | Self-contained fan | No fan required | 1-3 | 25 ℃,50% ~ 70% | >6.0 | less corrosive | 1-2 | >30 | ||
3. VHP disinfection working principle
vaporizes hydrogen peroxide liquid into hydrogen peroxide gas through high-temperature flash evaporation, and sprays it into the sterilization space through high-speed air flow. When high-temperature saturated hydrogen peroxide vapor contacts the surface of colder sterilized articles, it will form invisible micro-condensation, and attack pathogenic microorganisms (damage cell membranes, lipids, proteins and DNA) through the released strong oxidative free radicals (hydroxyl groups), which can achieve a log6 rapid killing effect on microorganisms. After the sterilization is completed, the vaporized hydrogen peroxide sterilization equipment will automatically decompose the hydrogen peroxide molecules in the environment into water vapor and oxygen, and the personnel can re-enter the clean area when the hydrogen peroxide concentration in the space drops below 1ppm.
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vaporized hydrogen peroxide sterilization process is divided into the following four operating stages:
the ventilation system of the facility is used to remove steam from the target area, or the ventilation unit is used to rapidly catalyze the decomposition of steam into water and oxygen. When the ventilation system of the facility does not have suitable valves or is not easy to control, it is very meaningful to use a separate ventilation system.
4. VHP space sterilization in the field of biosafety disinfection
VHP technology has been used for 20 years, and more than 85% of sterile isolators in the global pharmaceutical industry use VHP technology as the choice for biological decontamination. So far, VHP has been widely used in isolators, air filters, aseptic filling lines, high-level biosafety laboratories, infectious disease wards, isolation stretchers, ambulances and other different areas of disinfection treatment.
adopts direct injection to the sterilized room (the nozzle is generally placed in the center of the room, and VHP is directly injected into the environment, I .e. it does not need to be treated through a filter). Hydrogen peroxide vapor is directly injected into the work area, instead of high-efficiency filtration of air supply and exhaust, and the limitation on environmental conditions is removed. The cycle time can be completed within 1 h, and the work flow is obviously improved in some environments.
large area space disinfection, the elimination of any environmental conditions is necessary, foreign countries in the field of bioterrorism pollution elimination, sudden severe infectious disease disinfection, biological laboratory pollution disinfection. Domestic contamination elimination in biosafety tertiary laboratories, animal laboratories, large container groups, and food aseptic processing.
There are many successful reports on the elimination of contamination in biosafety tertiary laboratories, animal laboratories, large container groups, and food aseptic processing in China.
5. Validation
verification is an important part of GMP management in Chinese and foreign pharmaceutical enterprises. The definition of validation was first found in the "Drug Process Inspection Acceptance Criteria" (June 1978) published by the U.S. Food and Drug Administration FDA: "A validated process is a process that has been proven to operate as expected or claimed. Evidence of validation is obtained by collecting and evaluating, as far as possible, data from the development phase of the process, as well as data from subsequent production phases. Validation must include process validation (validation of materials, equipment, systems, buildings and personnel), as well as control of the entire process for batches or runs of repetitive production".
, China's newly promulgated "good manufacturing practice (revised in 2010)" defines verification as "a series of activities that prove that any operating procedure (or method), production process or system can achieve the expected results". The introduction of the concept of validation in GMP marks the upgrading of quality management from "quality inspection" to "quality assurance", which is known as a milestone in the history of GMP development.
The chemical gas fumigation sterilization of sterile drug clean area requires that it can be safely used on various surfaces such as stainless steel, steel, plastic, glass, epoxy floor, wall, etc., and carry out rapid and effective sterilization control on microorganisms including spores, and can pass the challenge test of biological indicator.
disinfection and sterilization methods is extremely important, and only through verification can the effectiveness and safety of disinfection and sterilization methods be confirmed. The requirements for sterile drugs adopt the latest World Health Organization and European Union A, B, C and D classifications, and put forward specific requirements for the cleanliness and level of sterile drug production. It is required to meet the dynamic A- level standard, and online monitoring is added, especially for the static and dynamic monitoring of suspended particles, and detailed regulations are made for the monitoring of plankton bacteria, sedimentation bacteria, microorganisms in the production environment and surface microorganisms.
| clean areas are as follows: | ||||
| cleanliness level | plankton cfu/m & sup3; | settling bacteria (Φ90mm)cfu/4 hours (2) | surface microorganisms | |
| contact (Φ55mm)cfu/disc | 5 Finger Gloves cfu/Gloves | |||
| Class A | <1 | <1 | <1 | <1 |
| Class B | 10 | 5 | 5 | 5 |
| Class C | 100 | 50 | 25 | - |
| Class D | 200 | 100 | 50 | - |
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Note: (1) All values in the table are average values. (2) The exposure time of a single settling dish can be less than 4 hours, and multiple settling dishes can be used in the same location for continuous monitoring and accumulation techniques. |
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At present, the vaporized hydrogen peroxide sterilization method has become a national pharmacopoeia, good manufacturing practice (GMP), disinfection and sterilization technical specifications recommend by the method, the sterilization process has been very mature, good repeatability, there are specialized commercial very standard chemical indicators and biological indicators used to detect the uniformity of hydrogen peroxide gas distribution in the sterilization process and the final sterilization effect.
Shanghai jiehao biotechnology co., ltd. adopts the latest third generation dry flash evaporation technology, which not only has stable flash temperature control, complete vaporization and small particle size of hydrogen peroxide gas generated, but also can set different injection rates at different stages of sterilization to improve material compatibility on the premise of ensuring sterilization effect. Compared with the closed-loop terminal spraying hydrogen peroxide gas, JIEHAO VHP vaporized hydrogen peroxide generator adopts open-loop gas circulation mode, and the cooperation of the gas distribution system makes the hydrogen peroxide gas distributed evenly, effectively expands the disinfection and sterilization volume, and the degradation rate has also been greatly improved.
