Sterilization (microbiology)

Sterilization (

Applications

Foods

One of the first steps toward modernized sterilization was made by

In the context of food, sterility typically refers to commercial sterility, "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 Allimentarius.^[5]

Medicine and surgery

In general, surgical instruments and medications that enter an already

Preparation of injectable medications and intravenous solutions for fluid replacement therapy requires not only sterility but also well-designed containers to prevent entry of adventitious agents after initial product sterilization.^[6]

Most medical and surgical devices used in healthcare facilities are made of materials that are able to go under steam sterilization.^[7] 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.^[8]

Spacecraft

There are strict international rules to protect the contamination of Solar System bodies from biological material from Earth. Standards vary depending on both the type of mission and its destination; the more likely a planet is considered to be habitable, the stricter the requirements are.^[9]

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 120 °C (248 °F), chemical sterilization, oxidization, ultraviolet, and irradiation.^[10]

Quantification

The aim of sterilization is the reduction of initially present microorganisms or other potential pathogens. The degree of sterilization is commonly expressed by multiples of the decimal reduction time, or D-value, denoting the time needed to reduce the initial number ${\displaystyle N_{0}}$ to one tenth (${\displaystyle 10^{-1}}$) of its original value.^[11] Then the number of microorganisms ${\displaystyle N}$ after sterilization time ${\displaystyle t}$ is given by:

${\displaystyle {\frac {N}{N_{0}}}=10^{\left(-{\frac {t}{D}}\right)}}$.

The D-value is a function of sterilization conditions and varies with the type of microorganism, temperature, water activity, pH etc.. For steam sterilization (see below) typically the temperature, in degrees Celsius, is given as an index.^{[citation needed]}

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.^{[citation needed]}

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 Food and Drug Administration (FDA).^[12]

Heat

Steam

Steam sterilization, also known as moist heat sterilization, uses heated

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. Indicator 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.^[16]

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.^[17]

Pressure cooking and canning is analogous to autoclaving, and when performed correctly renders food sterile.^{[18][failed verification]}

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.^{[citation needed]}

Dry

Dry heat was the first method of sterilization and is a longer process than moist heat sterilization. The destruction of microorganisms through the use of dry heat is a gradual phenomenon. With longer exposure to lethal temperatures, the number of killed microorganisms increases. Forced ventilation of hot air can be used to increase the rate at which heat is transferred to an organism and reduce the temperature and amount of time needed to achieve sterility. At higher temperatures, shorter exposure times are required to kill organisms. This can reduce heat-induced damage to food products.^[19]

The standard setting for a hot air oven is at least two hours at 160 °C (320 °F). A rapid method heats air to 190 °C (374 °F) for 6 minutes for unwrapped objects and 12 minutes for wrapped objects.^[20][21] Dry heat has the advantage that it can be used on powders and other heat-stable items that are adversely affected by steam (e.g. it does not cause rusting of steel objects).

Flaming

Flaming is done to

Incineration is a waste treatment process that involves the combustion of organic substances contained in waste materials. This method also burns any organism to ash. It is used to sterilize medical and other biohazardous waste before it is discarded with non-hazardous waste. Bacteria incinerators are mini furnaces that incinerate and kill off any microorganisms that may be on an inoculating loop or wire.^[22]

Tyndallization

Named after

Glass bead sterilizers

Glass bead sterilizers work by heating glass beads to 250 °C (482 °F). Instruments are then quickly doused in these glass beads, which heat the object while physically scraping contaminants off their surface. Glass bead sterilizers were once a common sterilization method employed in

Chemicals are also used for sterilization. Heating provides a reliable way to rid objects of all transmissible agents, but it is not always appropriate if it will damage heat-sensitive materials such as biological materials,

Eniware, LLC has developed a portable, power-free sterilizer that uses no electricity, heat or water.[39] 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 four hour cycle uses a single use gas generation ampoule and a disposable scrubber to remove nitrogen dioxide gas.^[40]

Ozone

oxidize most organic matter. On the other hand, it is a toxic and unstable gas that must be produced on-site, so it is not practical to use in many settings.^{[citation needed}

]

Ozone offers many advantages as a sterilant gas; ozone is a very efficient sterilant because of its strong oxidizing properties (

medical-grade oxygen. The high reactivity of ozone means that waste ozone can be destroyed by passing over a simple catalyst 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 immediately dangerous to life and health limit (IDLH) for ozone is 5 ppm, 160 times smaller than the 800 ppm IDLH for ethylene oxide. NIOSH^[42]

and OSHA has set the PEL for ozone at 0.1 ppm, calculated as an eight-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.

Glutaraldehyde and formaldehyde

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Salk polio vaccine

, are sterilized with formaldehyde.

Hydrogen peroxide

oxidant, which allows it to destroy a wide range of pathogens. Hydrogen peroxide is used to sterilize heat- or temperature-sensitive articles, such as rigid endoscopes. In medical sterilization, hydrogen peroxide is used at higher concentrations, ranging from around 35% up to 90%. The biggest advantage of hydrogen peroxide as a sterilant is the short cycle time. Whereas the cycle time for ethylene oxide may be 10 to 15 hours, some modern hydrogen peroxide sterilizers have a cycle time as short as 28 minutes.^[43]

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

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,^[33] less than one tenth 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 eight-hour time-weighted average.^[45] 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 MAUDE database.^[46] 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.^[47][48]

Vaporized hydrogen peroxide (VHP) is used to sterilize large enclosed and sealed areas, such as entire rooms and aircraft interiors.

Although toxic, VHP breaks down in a short time to water and oxygen.

Peracetic acid

Peracetic acid (0.2%) is a recognized sterilant by the FDA^[49] for use in sterilizing medical devices such as endoscopes. Peracetic acid which is also known as peroxyacetic acid is a chemical compound often used in disinfectants such as sanitizers. It is most commonly produced by the reaction of acetic acid and hydrogen peroxide with each other by using an acid catalyst. Peracetic acid is never sold in unstabilized solutions which is why it is considered to be environmentally friendly.^[50] Peracetic acid is a colorless liquid and the molecular formula of peracetic acid is C₂H₄O₃ or CH3COOOH.^[51] More recently, peracetic acid is being used throughout the world as more people are using fumigation to decontaminate surfaces to reduce the risk of COVID-19 and other diseases.^[52]

Potential for chemical sterilization of prions

Prions are highly resistant to chemical sterilization.^[53] Treatment with aldehydes, such as formaldehyde, have actually been shown to increase prion resistance. Hydrogen peroxide (3%) for one hour was shown to be ineffective, providing less than 3 logs (10⁻³) reduction in contamination. Iodine, formaldehyde, glutaraldehyde, and peracetic acid also fail this test (one hour treatment).^[54] Only chlorine, phenolic compounds, guanidinium thiocyanate, and sodium hydroxide reduce prion levels by more than 4 logs; chlorine (too corrosive to use on certain objects) and sodium hydroxide are the most consistent. Many studies have shown the effectiveness of sodium hydroxide.^[55]

Radiation sterilization

Sterilization can be achieved using

electron beams.^[56] Electromagnetic or particulate radiation can be energetic enough to ionize atoms or molecules (ionizing radiation), or less energetic (non-ionizing radiation).^{[citation needed}

]

Non-ionizing radiation sterilization

Further information: Ultraviolet germicidal irradiation

Ultraviolet light irradiation (UV, from a

biological safety cabinets between uses, but is ineffective in shaded areas, including areas under dirt (which may become polymerized after prolonged irradiation, so that it is very difficult to remove).^[57] It also damages some plastics, such as polystyrene

foam if exposed for prolonged periods of time.

Ionizing radiation sterilization

The safety of irradiation facilities is regulated by the International Atomic Energy Agency of the United Nations and monitored by the different national Nuclear Regulatory Commissions (NRC). The radiation exposure accidents that have occurred in the past are documented by the agency and thoroughly analyzed to determine the cause and improvement potential. Such improvements are then mandated to retrofit existing facilities and future design.

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 use dry storage, providing movable shields that reduce radiation levels in areas of the irradiation chamber. An incident in Decatur, Georgia, US, where water-soluble caesium-137 leaked into the source storage pool, requiring NRC intervention^[58] has led to use of this radioisotope being almost entirely discontinued in favour of the more costly, non-water-soluble cobalt-60. Cobalt-60 gamma photons have about twice the energy, and hence greater penetrating range, of caesium-137-produced radiation.

Electron beam processing is also commonly used for sterilization. Electron beams 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 electrons 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.^[59]

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.

radioactive, because the energy used is too low. Generally an energy of at least 10 MeV is needed to induce radioactivity in a material.^[60] Neutrons

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.[61]^[62]

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 sterilized by irradiation.^[63]

Subatomic particles may be more or less penetrating and may be generated by a radioisotope or a device, depending upon the type of particle.

Sterile filtration

Fluids that would be damaged by heat, irradiation or chemical sterilization, such as drug solution, can be sterilized by

biologics, viruses must be removed or inactivated, requiring the use of nanofilters with a smaller pore size (20–50 nm). Smaller pore sizes lower the flow rate, so in order to achieve higher total throughput or to avoid premature blockage, pre-filters might be used to protect small pore membrane filters. Tangential flow filtration

(TFF) and alternating tangential flow (ATF) systems also reduce particulate accumulation and blockage.

Membrane filters used in production processes are commonly made from materials such as mixed

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 the filter is undamaged and is a regulatory requirement.^[66] Typically, terminal pharmaceutical sterile filtration is performed inside of a cleanroom

to prevent contamination.

Preservation of sterility

Instruments that have undergone sterilization can be maintained in such condition by containment in sealed packaging until use.

Aseptic technique is the act of maintaining sterility during procedures.

See also

• Antibacterial soap
• Asepsis
• Aseptic processing
• Contamination control
• Electron irradiation
• Food packaging
• Food preservation
• Food safety
• Spaulding classification
• Sterilant gas monitoring

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