Product Code Database
Sterilization () refers to any process that removes, kills, or deactivates all forms of life (particularly such as fungi, bacteria, , and unicellular eukaryotic organisms) and other (such as or ) present in fluid or on a specific surface or object. Sterilization can be achieved through various means, including heat, , irradiation, high pressure, and filtration. Sterilization is distinct from disinfection, sanitization, and pasteurization, in that those methods reduce rather than eliminate all forms of life and biological agents present. After sterilization, fluid or an object is referred to as being sterile or aseptic.
In the context of food, sterility typically refers to commercial sterility, defined as "the absence of microorganisms capable of growing in the food at normal non-refrigerated conditions at which the food is likely to be held during distribution and storage" according to the Codex Alimentarius. (see also 21 CFR 113, a definition focused on thermal processing)
Preparation of injectable medications and intravenous solutions for fluid replacement therapy requires not only sterility but also well-designed containers to prevent entry of infection after initial product sterilization.
Most medical and surgical devices used in healthcare facilities are made of materials that are able to undergo steam sterilization. However, since 1950, there has been an increase in medical devices and instruments made of materials (e.g., plastics) that require low-temperature sterilization. Ethylene oxide gas has been used since the 1950s for heat- and moisture-sensitive medical devices. Within the past 15 years, a number of new, low-temperature sterilization systems (e.g., vaporized hydrogen peroxide, peracetic acid immersion, ozone) have been developed and are being used to sterilize medical devices.
Many components of instruments used on spacecraft cannot withstand very high temperatures, so techniques not requiring excessive temperatures are used as tolerated, including heating to at least , chemical sterilization, oxidization, ultraviolet, and irradiation.
where is the number of viable microorganisms, is the sterilization time, and is the specific death rate constant. Integration yields:
where is the initial number of microorganisms.
The degree of sterilization is often quantified using the decimal reduction time, or D-value, defined as the time required to reduce by one logarithmic unit (i.e to ) or when initial population is reduced by one-tenth (). The surviving population after time t can then be expressed as:
The D-value is a function of sterilization conditions and varies with the type of microorganism, temperature, water activity, pH, etc..
As in any first-order reaction, the reaction rate increases with temperature due to an increase in the rate constant . For thermal destruction of microorganisms, the specific death rate remains constant at constant temperature. The dependence of on temperature follows the Arrhenius relationship:
where is a constant known as Arrhenius factor, is the activation energy, is the gas constant, and is absolute temperature. Now, combining the first-order death kinetics with the Arrhenius equation results in the following expression for heat sterilization of a pure culture at constant temperature:
or,
Theoretically, the likelihood of the survival of an individual microorganism is never zero. To compensate for this, the overkill method is often used. Using the overkill method, sterilization is performed by sterilizing for longer than is required to kill the bioburden present on or in the item being sterilized . This provides a sterility assurance level (SAL) equal to the probability of a non-sterile unit.
For high-risk applications, such as medical devices and injections, a sterility assurance level of at least 10−6 is required by the United States of America Food and Drug Administration (FDA).
Proper autoclave treatment will inactivate all resistant bacterial in addition to fungi, bacteria, and viruses, but is not expected to eliminate all , which vary in their heat resistance. For prion elimination, various recommendations state for 60 minutes or for at least 18 minutes. The 263K scrapie prion is inactivated relatively quickly by such sterilization procedures; however, other strains of scrapie and strains of Creutzfeldt-Jakob disease (CKD) and bovine spongiform encephalopathy (BSE) are more resistant. Using laboratory mouse as test animals, one experiment showed that heating BSE positive brain tissue at for 18 minutes resulted in only a 2.5 logarithm decrease in prion infectivity.
Most autoclaves have meters and charts that record or display information, particularly temperature and pressure as a function of time. The information is checked to ensure that the conditions required for sterilization have been met. Autoclave tape is often placed on the packages of products prior to autoclaving, and some packaging incorporates indicators. The indicator changes color when exposed to steam, providing a visual confirmation.
Biological indicators can also be used to independently confirm autoclave performance. Simple biological indicator devices are commercially available, based on microbial spores. Most contain spores of the heat-resistant microbe Geobacillus stearothermophilus (formerly Bacillus stearothermophilus), which is extremely resistant to steam sterilization. Biological indicators may take the form of glass vials of spores and liquid media, or as spores on strips of paper inside glassine envelopes. These indicators are placed in locations where it is difficult for steam to reach to verify that steam is penetrating that area.
For autoclaving, cleaning is critical. Extraneous biological matter or grime may shield organisms from steam penetration. Proper cleaning can be achieved through physical scrubbing, sonication, ultrasound, or pulsed air.
Pressure cooking and canning is analogous to autoclaving, and when performed correctly renders food sterile.
To sterilize waste materials that are chiefly composed of liquid, a purpose-built effluent decontamination system can be utilized. These devices can function using a variety of sterilants, although using heat via steam is most common.
2008-09-11 They are still popular in and dental practices, although there are no current evidence-based guidelines for using this sterilizer.
Ethylene oxide treatment is generally carried out between with relative humidity above 30% and a gas concentration between 200 and 800 mg/L. Typically, the process lasts for several hours. Ethylene oxide is highly effective, as it penetrates all porous materials, and it can penetrate through some plastic materials and films. Ethylene oxide kills all known microorganisms, such as bacteria (including spores), viruses, and fungi (including yeasts and moulds), and is compatible with almost all materials even when used repeatedly. It is flammable, toxic, and ; however, only with a reported potential for some adverse health effects when not used in compliance with published requirements. Ethylene oxide sterilizers and processes require biological validation after sterilizer installation, significant repairs, or process changes.
The traditional process consists of a preconditioning phase (in a separate room or cell), a processing phase (more commonly in a vacuum vessel and sometimes in a pressure rated vessel), and an aeration phase (in a separate room or cell) to remove EO residues and lower by-products such as ethylene chlorohydrin (EC or ECH) and, of lesser importance, ethylene glycol (EG). An alternative process, known as all-in-one processing, also exists for some products whereby all three phases are performed in the vacuum or pressure rated vessel. This latter option can facilitate faster overall processing time and residue dissipation.
The most common EO processing method is the gas chamber. To benefit from economies of scale, EO has traditionally been delivered by filling a large chamber with a combination of gaseous EO, either as pure EO, or with other gases used as diluents; diluents include chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and carbon dioxide.
Ethylene oxide is still widely used by medical device manufacturers.Mendes GCC, Brandão TRS, Silva CLM. 2007. Ethylene oxide sterilization of medical devices: A review. Am J Infect Control. Since EO is explosive at concentrations above 3%, EO was traditionally supplied with an Inert gas carrier gas, such as a CFC or HCFC. The use of CFCs or HCFCs as the carrier gas was banned because of concerns of ozone depletion. These halogenated hydrocarbons are being replaced by systems using 100% EO, because of regulations and the high cost of the blends. In hospitals, most EO sterilizers use single-use cartridges because of the convenience and ease of use compared to the former plumbed gas cylinders of EO blends.
It is important to adhere to patient and healthcare personnel government specified limits of EO residues in and/or on processed products, operator exposure after processing, during storage and handling of EO gas cylinders, and environmental emissions produced when using EO.
The U.S. Occupational Safety and Health Administration (OSHA) has set the permissible exposure limit (PEL) at 1 ppm – calculated as an 8-hour time-weighted average (TWA) – and 5 ppm as a 15-minute excursion limit (EL). The National Institute for Occupational Safety and Health's (NIOSH) immediately dangerous to life and health limit (IDLH) for EO is 800 ppm. The Odor Threshold is around 500 ppm, so EO is imperceptible until concentrations are well above the OSHA PEL. Therefore, OSHA recommends that continuous gas monitoring systems be used to protect workers using EO for processing.
The most-resistant organism (MRO) to sterilization with NO2 gas is the spore of Geobacillus stearothermophilus, which is the same MRO for both steam and hydrogen peroxide sterilization processes. The spore form of G. stearothermophilus has been well characterized over the years as a biological indicator in sterilization applications. Microbial inactivation of G. stearothermophilus with NO2 gas proceeds rapidly in a Log-linear graph fashion, as is typical of other sterilization processes. Noxilizer, Inc. has commercialized this technology to offer contract sterilization services for medical devices at its Baltimore, Maryland (USA) facility. This has been demonstrated in Noxilizer's lab in multiple studies and is supported by published reports from other labs. These same properties also allow for quicker removal of the sterilant and residual gases through aeration of the enclosed environment. The combination of rapid lethality and easy removal of the gas allows for shorter overall cycle times during the sterilization (or decontamination) process and a lower level of sterilant residuals than are found with other sterilization methods. Eniware, LLC has developed a portable, power-free sterilizer that uses no electricity, heat, or water. The 25 liter unit makes sterilization of surgical instruments possible for austere forward surgical teams, in health centers throughout the world with intermittent or no electricity and in disaster relief and humanitarian crisis situations. The 4-hour cycle uses a single use gas generation ampoule and a disposable scrubber to remove NO2 gas.
Ozone offers many advantages as a sterilant gas; ozone is a very efficient sterilant because of its strong oxidizing properties (Oxidation number=2.076 vs SHE) capable of destroying a wide range of pathogens, including prions, without the need for handling hazardous chemicals since the ozone is generated within the sterilizer from medical-grade oxygen. The high reactivity of ozone means that waste ozone can be destroyed by passing over a simple Catalysis that reverts it to oxygen and ensures that the cycle time is relatively short. The disadvantage of using ozone is that the gas is very reactive and very hazardous. The NIOSH's IDLH for ozone is smaller than the IDLH for ethylene oxide. NIOSH and OSHA have set the PEL for ozone at , calculated as an 8-hour time-weighted average. The sterilant gas manufacturers include many safety features in their products but prudent practice is to provide continuous monitoring of exposure to ozone, in order to provide a rapid warning in the event of a leak. Monitors for determining workplace exposure to ozone are commercially available.
Drawbacks of hydrogen peroxide include material compatibility, a lower capability for penetration and operator health risks. Products containing cellulose, such as paper, cannot be sterilized using VHP and products containing nylon may become brittle. The penetrating ability of hydrogen peroxide is not as good as ethylene oxide and so there are limitations on the length and diameter of the lumen of objects that can be effectively sterilized. Hydrogen peroxide is a primary irritant and the contact of the liquid solution with skin will cause Skin whitening or ulceration depending on the concentration and contact time. It is relatively non-toxic when diluted to low concentrations, but is a dangerous oxidizer at high concentrations (> 10% w/w). The vapour is also hazardous, primarily affecting the eyes and respiratory system. Even short-term exposures can be hazardous and NIOSH has set the IDLH at 75 ppm, less than 1/10 the IDLH for ethylene oxide (800 ppm). Prolonged exposure to lower concentrations can cause permanent lung damage and consequently, OSHA has set the permissible exposure limit to 1.0 ppm, calculated as an 8-hour time-weighted average. Sterilizer manufacturers go to great lengths to make their products safe through careful design and incorporation of many safety features, though there are still workplace exposures of hydrogen peroxide from gas sterilizers documented in the FDA Manufacturer and User Facility Device Experience (MAUDE) database. When using any type of gas sterilizer, prudent work practices should include good ventilation, a continuous gas monitor for hydrogen peroxide, and good work practices and training.
Vaporized hydrogen peroxide (VHP) and ionized hydrogen peroxide (iHP) are used to sterilize large enclosed and sealed areas, such as entire rooms and aircraft interiors.
VHP and iHP break down in a short time to water and oxygen.
Gamma Radiation is very penetrating, and is commonly used for sterilization of disposable medical equipment, such as syringes, needles, and IV sets, and food. It is emitted by a radioisotope, usually cobalt-60 (60Co) or caesium-137 (137Cs), which have photon energies of up to 1.3 and 0.66 MeV, respectively.
Use of a radioisotope requires shielding for the safety of the operators while in use and in storage. With most designs, the radioisotope is lowered into a water-filled source storage pool, which absorbs radiation and allows maintenance personnel to enter the radiation shield. One variant keeps the radioisotope under water at all times and lowers the product to be irradiated in the water in hermetically sealed bells; no further shielding is required for such designs. Other uncommonly used designs are dry storage, providing movable shields that reduce radiation levels in areas of the irradiation chamber, etc. An incident in Decatur, Georgia, USA, where water-soluble caesium-137 leaked into the source storage pool, required Nuclear Regulatory Commission (NRC) intervention and led to the use of this radioisotope being almost entirely discontinued in favor of the more costly, non-water-soluble cobalt-60. Cobalt-60 gamma have about twice the energy, and hence greater penetrating range, of caesium-137-produced radiation.
Electron beam processing is also commonly used for sterilization. Cathode ray use an on-off technology and provide a much higher dosing rate than gamma or X-rays. Due to the higher dose rate, less exposure time is needed and thereby any potential degradation to polymers is reduced. Because carry a charge, electron beams are less penetrating than both gamma and X-rays. Facilities rely on substantial concrete shields to protect workers and the environment from radiation exposure.
High-energy X-rays (produced by bremsstrahlung) allow irradiation of large packages and pallet loads of medical devices. They are sufficiently penetrating to treat multiple pallet loads of low-density packages with very good dose uniformity ratios. X-ray sterilization does not require chemical or radioactive material: high-energy X-rays are generated at high intensity by an X-ray generator that does not require shielding when not in use. X-rays are generated by bombarding a dense material (target) such as tantalum or tungsten with high-energy electrons, in a process known as bremsstrahlung conversion. These systems are energy-inefficient, requiring much more electrical energy than other systems for the same result.
Irradiation with X-rays, gamma rays, or electrons does not make materials radioactive, because the energy used is too low. Generally an energy of at least 10 MeV is needed to induce radioactivity in a material. and very high-energy particles can make materials radioactive, but have good penetration, whereas lower energy particles (other than neutrons) cannot make materials radioactive, but have poorer penetration.
Sterilization by irradiation with gamma rays may however affect material properties.
Irradiation is used by the United States Postal Service to sterilize mail in the Washington, D.C. area. Some foods (e.g., spices and ground meats) are food irradiation.
Subatomic particles may be more or less penetrating and may be generated by a radioisotope or a device, depending upon the type of particle.
Membrane filters used in production processes are commonly made from materials such as mixed cellulose ester or polyethersulfone (PES). The filtration equipment and the filters themselves may be purchased as pre-sterilized disposable units in sealed packaging or must be sterilized by the user, generally by autoclaving at a temperature that does not damage the fragile filter membranes. To ensure proper functioning of the filter, the membrane filters are integrity tested post-use and sometimes before use. The nondestructive integrity test assures that the filter is undamaged and is a regulatory requirement. Typically, terminal pharmaceutical sterile filtration is performed inside of a cleanroom to prevent contamination.
Aseptic technique is the act of maintaining sterility during procedures.
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