目录

1. Dry heat.................................................................................................................................3
Introduce:...........................................................................................................................3
What Is Sterilization By Dry Heat?.................................................................................3
What Items Can Be Sterilized By Dry Heat?................................................................3
How Is Sterilization By Dry Heat Performed?..............................................................3
What Are The Problems With Sterilization By Dry Heat?..........................................4
2. Gamma rays.........................................................................................................................4
Introduce:...........................................................................................................................4
How Is Gamma Sterilization Performed?......................................................................4
Some Benefits Of Gamma Sterilization Are:................................................................5
Some Of The Drawbacks To Gamma Sterilization Are:.............................................5
3.Electron beam.......................................................................................................................6
How Is Electron Beam Sterilization Performed............................................................6
Factors That Affect Electron Beam Sterilization:.........................................................8
Disadvantage:...................................................................................................................9
Standards:..........................................................................................................................9
4.eto sterilizer............................................................................................................................10
What Are Ethylene Oxide And Sterilization By Ethylene Oxide?............................10
How Is Sterilization By Ethylene Oxide Performed?.................................................11
Factors That Affect EO Sterilization And Lethality:...................................................12
5.NO2 Sterilization.................................................................................................................13
6. Steam Sterilization (Sterilization By Moist Heat)..........................................................14
What Is Steam Sterilization (Sterilization By Moist Heat)?......................................14
How Is Steam Sterilization Performed?......................................................................15
USAGE:............................................................................................................................15
What Are The Advantages And Disadvantages Of Steam Sterilization?..............15
7. x-ray.....................................................................................................................................16
What is X-ray Irradiation?..............................................................................................16
What are the Benefits of X-ray Irradiation Processing?...........................................16
Standards:........................................................................................................................17
8. plasma sterilizer................................................................................................................17
Application.......................................................................................................................17
Advantages of Hydrogen Peroxide Plasma................................................................18
Disadvantages of Hydrogen Peroxide Plasma..........................................................18
9.Formaldehyde sterilization................................................................................................18
Usage...............................................................................................................................18
Not So Welcomed Around the World..........................................................................19
Advantages of formaldehyde steam sterilization.......................................................19
Disadvantages of formaldehyde gas sterilization......................................................19
Comparison table...................................................................................................................20
Comparison table between Radiation sterilization....................................................20
Summary of advantages and disadvantages of commonly used sterilization
technologies....................................................................................................................23
1. Dry heat

Introduce:

Dry heat in the form of hot air is used primarily to sterilise hydrophilic materials or materials that

steam and ethylene oxide gas cannot penetrate such as anhydrous oils, petroleum products,

and bulk powders. Typically used parameters for dry heat sterilisation are 2 hours holding time

at 160°C, but other temperatures up to 180°C can be used, for example 1 hour holding time at

170°C or 30 minutes at 180°C.

Although heating provides the most reliable way to rid objects of all transmissible agents,

steam and dry heat sterilisation may be overly aggressive for device components or sterile

barrier materials and cannot be used for those that are heat or moisture sensitive.

What Is Sterilization By Dry Heat?

Heat-based sterilization methods kill microorganisms by denaturing proteins within the cells.

Lethality Of Microorganisms Depends On:

1. Degree of heat exposure

2. Duration of heat exposure

3. Moisture level

What Items Can Be Sterilized By Dry Heat?

Items typically sterilized by dry heat are glassware, metal parts, oils, and some dry powders.

How Is Sterilization By Dry Heat Performed?

Sterilization by dry heat is a simple process where loaded items are placed into a heating cabinet or

conveyor tunnel. Items to be sterilized are then exposed to high temperatures for an extended time, and

filtered air blower fans enable the heat to be uniformly distributed in the sterilizer. Dry heat is both

simple and one of the most effective ways to destroy endotoxins. Temperatures for depyrogenation are

a minimum of 250◦C. Thus, depyrogenation via dry heat requires higher temperatures (and often longer

exposure times) than dry heat sterilization alone. An additional advantage of dry heat sterilization is that

the sterilized materials are dry at the end of the sterilization cycle, so there is no risk of metals corroding

after sterilization. Further, unlike in gas sterilization, off-gassing time and residuals testing are not

needed.

What Are The Problems With Sterilization By Dry Heat?

The greatest problem with sterilization by dry heat is that the sterilization process is slow. Thus, dry heat

sterilization can only sterilize items capable of holding their integrity at high heat for long periods.

Additionally, the dry heat sterilization process is difficult to control within precise temperature limits,

which is why the USP states that an acceptable operating temperature range for the empty chamber is ±

15◦C.

2. Gamma rays

Introduce:

Gamma is a radiation sterilization method. Gamma rays are created by the self-disintegration of Cobalt-

60 (60Co) or Cesium-137 (137Cs). Gamma rays are highly penetrating and can inactivate microbes with

more depth than e-beam beta particles. The thickness and density of a material determine the level of

gamma penetration.

How Is Gamma Sterilization Performed?

Gamma sterilization is very similar to electron beam sterilization. The difference is that gamma rays

created by the self-disintegration of Cobalt-60 (60Co) or Cesium-137 (137Cs) are used within radiation

conveyors instead of beta particles. Gamma radiation also generally takes a longer exposure time than

electron beam radiation. However, factors that affect electron beam sterilization and the overall

sterilization process through a radiation sterilization conveyor system are the same. Gamma dosage is

verified utilizing dosimeters stationed at various points throughout the radiation sterilization conveyor.

Some Benefits Of Gamma Sterilization Are:

 Gamma sterilization is an advanced technological method.

 Gamma sterilization is a cold method, and the increase in temperature is slight.

 Gamma has a high SAL.

 Control of the gamma sterilization is easy and can only be made by varying the applied dose.

 Gamma radiation has great penetration and can easily provide terminal sterilization for products

in their final packages.

 Gamma radiation can be used for drug delivery systems such as microspheres, liposomes, or

monoclonal antibodies.

 Gamma radiation processes are easily validated. Time changes for gamma sterilization cycles

only shift when the 60Co source decomposes at a constant speed. Otherwise, gamma radiation

is constant and can be controlled by controlling the dwell time/speed of the conveyor in every

position while it turns around the radiative source.

 Products sterilized with gamma radiation can be immediately released and do not require batch-

to-batch sterility testing.

 Gamma radiation exposure can reduce endotoxins (depyrogenate products).

 Gamma radiation forms no residue after the sterilization process.

Some Of The Drawbacks To Gamma Sterilization Are:

 The dose rate is lower than electron beams.

  Gamma radiation has limited dose flexibility.

Usage: Gamma radiation can easily be applied to many materials. However, gamma sterilization is

incompatible with polyvinyl chloride (PVC), acetal, and polytetrafluoroethylene (PTFE). Standard

devices and materials sterilized with gamma radiation are plastics, heat-labile materials, glass, and

powders. Gamma is generally used to sterilize disposable medical equipment, medical devices, and

implants such as arteriovenous shunts, peritoneal dialysis sets, aortic valves, peripheral vascular

prosthesis, dental implants, and artificial eyelids. Radiation damages the nucleoproteins of

microorganisms, and thus, gamma sterilization is not recommended for most biologics. However, certain

devices with microspheres, liposomes, or monoclonal antibodies may be sterilized with gamma.

Standards:

Gamma sterilization is supported by the internationally recognized consensus standard, ISO 11137,

which describes the approach to validating a dose to achieve a defined sterility assurance level (SAL).

3.Electron beam

How Is Electron Beam Sterilization Performed

Simply speaking, e-beam sterilization is performed by exposing a product to beta particles. Beta

particles are not electromagnetic and less penetrative than ionizing gamma radiation. However, most e-

beam sterilization requires an electron accelerator, a rare and specialized machine. In electron

accelerator systems, electrons are accelerated to near the speed of light and at high electron

concentrations. Electron absorption by the product undergoing sterilization destroys the DNA of any live

microbes. The mechanism of microbial DNA destruction is called DNA chain cleavage. DNA chain

cleavage occurs by changing the DNA’s chemical and molecular bonds.

E-beam sterilization cycle characteristics depend on accelerated energy and adsorbed dose. The

absorbed dose is the amount of interaction between the e-beam and the product that will be sterilized.

The adsorbed dose is often defined as the absorbed energy per unit mass (Jewels per kilogram).

Absorbed dose and absorption depth depend on the acceleration energy. Further, the microbial survival

fraction is inversely proportional to the absorbed dose. Thus, the higher the absorbed dose, the smaller

the fraction of surviving microbes.

Electron beam radiation effectiveness is dependent on the radiation dosage and time exposure. A 12-D

sterilization overkill approach is often used for electron beam sterilization. The 12-D stands for providing

a radiation dose sufficient to produce a 12-log reduction in the D-value of the most resistant microbial

spore. Note that D-value determination for radiation uses dosage rather than time. A typical D-value

range for the most resistant bacterial spore (Bacillus pumulis) to radiation is 1.7 to 2.0 megarad (MRad).

A 12-D radiation dosage of 25 mRad is common, as this dosage is greater than 12-fold the D value of B.

pumulis. However, the total radiation dose for e-beam sterilized products with tissue materials is in the

range of 2 Mrad.

When a product goes through an e-beam sterilization conveyor (see Figure 1 below), the product moves

under the e-beam at a set speed to obtain the desired electron dosage for the sterilization process. The

total radiation dosage is distributed throughout the conveyor system so that there is no change in dose

over time. An e-beam sterilization process can be adjusted by altering conveyor speed, which impacts

the applied dose of the beam current.

Factors That Affect Electron Beam Sterilization:

1. D value of the biological indicator or bioburden level of the item undergoing sterilization

2. Radiation strength (accelerated energy)

3. Radiation dose rate (absorbed dose)

4. Conveyor speed

Usage:Standard devices and materials sterilized with electron beam are plastics, heat-labile materials,

glass, and powders. E-beam irradiation can also be used for tissue materials like aortas, bone,

cardiovascular valves, and hydrogels. Radiation damages the nucleoproteins of microorganisms, and

thus, electron beam sterilization is not recommended for biologics.

Advantage:

E-beam sterilization is an internationally accepted and FDA-approved process.

  E-beam has a high dosing rate and sterility assurance level (SAL), allowing for immediate

release (no batch-to-batch sterility testing is needed after sterile processing)

 E-beam can penetrate a variety of materials, including foils.

 E-beam processes allow for temperature control during irradiation.

 A well-controlled dose range can be achieved with e-beam sterilization.

 E-beam sterilization is cost-effective.

 E-beam sterilization is a fast process (a minute in small lots), allowing near-immediate access to

fully sterilized products.

 The speed of e-beam dosing protects the product’s material properties, prevents polymer

degradation, and causes no damage to sterile seals on product packaging.

 E-beam has a minimal atmospheric effect and only releases a slight amount of ozone.

 E-beam sterilization doesn’t require a localized radioactive source.

Disadvantage:

 E-beam sterilization institution construction is expensive.

 There are few e-beam radiation sterilization centers available for bulk sterilization.

 E-beam sterilization is less penetrative than radiation sterilization utilizing gamma.

 A concern when sterilizing finished products or active pharmaceutical ingredients (APIs) with

beta particles is the risk of radiolytic byproduct formation (e.g., *OH) that could cause damage to

the raw material, API, or product packaging system.

Standards:

Electron beam sterilization is supported by the internationally recognized consensus standard, ISO

11137, which describes the approach to validating a process to achieve a defined sterility assurance

level (SAL).
4.eto sterilizer

What Are Ethylene Oxide And Sterilization By Ethylene Oxide?

Ethylene oxide (ETO or EO) is a gas commonly used to sterilize medical devices and products

chemically. Ethylene oxide is a potent and highly penetrating alkylating agent. These characteristics

make it an extremely effective sterilizing agent and a standard sterilization method for medical devices.

However, at certain levels, ethylene oxide is also capable of causing cancer. ETO medical device

sterilization kills microorganisms through exposure to ethylene oxide gas under vacuum and humidity.

ETO is used either as 100% ETO or in combination with carbon dioxide.

Usage :1.Endoscopes: Throat scopes, bronchoscopes, esophagoscopes, cystoscopes and

ureteroscopes, mediastinoscopes, thoracoscopes, esophageal fiberscopes, gastric fiberscopes,

duodenal fiberscopes, bronchial fiberscopes, vascular fiberscopes, etc.

2.Plastic and rubber products: Gloves, finger cots, syringes, injection devices, blood collection

devices, infusion devices, urine collection bags, test tubes, intracranial catheters, venous catheters,

arterial catheters, hoses, catheters, sponges, linings, etc.

3.Instruments and equipment: Surgical room automatic suturing machines, sutures, suturing

needles, artificial esophagus, artificial bones, artificial pericardial membranes, artificial blood vessels,

polytetrafluoroethylene artificial membranes, artificial lung circuits, pacemakers, pacemaker

electrodes, drainage devices, postoperative suction devices, lumbar puncture devices, urinary

catheterization devices, abdominal dialysis circuits, thermistors, stethoscopes, medical electric drills,

medical electric saws, electric knives, batteries, bone plates, cameras, etc.

4.Anesthetic vessels: Endotracheal tubes, nasal tubes, tracheostomy tubes, suction tubes,

anesthesia masks, corrugated tubes, anesthesia bags, closed circulation loops, artificial respiration

components, atomizers, oxygen tents, etc.

 5.Cotton fiber products and others: Clothes, gauze, bandages, cotton balls, cotton swabs, defatted

cotton, towels, blankets, surgical gowns, surgical caps, brushes, bedding, pillowcases, mattresses,

bedding, books, toys, etc.

 ISO 11135, Sterilization of health care products – Ethylene oxide – Requirements for development,

validation, and routine control of a sterilization process for medical devices.

How Is Sterilization By Ethylene Oxide Performed?

A typical ethylene oxide sterilization cycle is shown in Figure 2. The exposure time for most EO

sterilizations is relatively long (around 6 hours). The gas aeration period is also lengthy, up to 24 hours

or more. After loading items into an ethylene oxide sterilization chamber, a vacuum is applied. Next, the

chamber is filled to the desired relative humidity. Then an appropriate concentration of EO gas is added.

Items undergoing sterilization rest in the EO gas under vacuum and humidity for the desired exposure

time. Finally, the gas is slowly and safely evacuated from the EO sterilization chamber, and the

sterilized items are given ample aeration time to support EO off-gassing. For sterilization validations, the

D value of biological indicators used for EO sterilization validations may range up to 10-fold over the

range of relative humidity values.

Figure 2. Graph of a 100 per cent ethylene oxide sterilization cycle

Factors That Affect EO Sterilization And Lethality:

1. Gas concentration—Ranges is 400 to 1200 milligrams per liter

2. Temperature—Temperature depends on the gas concentration. Most EO cycles range from

50◦C to 60◦C.

3. Relative humidity—Humidity traditionally ranges from 35% to 80% relative humidity.

4. Exposure time— Exposure time varies based on materials used, gas concentration,

temperature, and relative humidity.

Advantage:

Sterilization at Low Temperatures

Ensures the integrity of both the product and packaging

Product Compatibility

Effectively sterilizes a broad range of polymers, resins, natural materials, and metals as well as dual

drug-device combination products that require external contact surface sterilization

Sterility Assurance and Treatment Efficacy

Consistently meets product and regulatory requirements

Flexibility and Versatility

Effectively sterilizes a wide range of products with different variations in dose requirements, densities,

and packaging/box sizes

Parametric Release

Allows for the release of products directly after processing which results in fast turn times to help get

products to market rapidly

Disadvantages :

Excessvely Long cycle

Safety concerns - carcinogenic to humans

Toxicity issues - toxic residues on surgical instruments and tubing

Not recommended for flexible scope

5.NO2 Sterilization

Nitrogen dioxide gas sterilization is ideal for sensitive biotech products and improves supply chain

efficiency:

ADVANTAGE:

 Ultra-low temperature sterilization (10°C – 30°C) — maintains drug integrity

 Minimal vacuum option — prevents stopper movement

 Surface sterilization process — does not leach through the stopper

 Short cycle times (6-12 hours) including aeration

 Safe and easy to bring in house — reduces manufacturing time and cost
 Compatible Materials

Stainless Steel Polyethylene Polyetherimide Thermoplastic Elastomers

Aluminum Polypropylene Polycarbonate

Gold (Plating) PET/PETG Cyclic Olefins

Glass/Ceramic Polystyrene PVC*

Fluoropolymers Polysulfones Silicone* This list is not exhaustive

Viton (Gaskets) PEEK/PAEK Hypalon

6. Steam Sterilization (Sterilization By Moist Heat)

What Is Steam Sterilization (Sterilization By Moist Heat)?

Steam sterilization (also known as moist heat sterilization) is performed in an autoclave. Moist heat

sterilization destroys microorganisms on (or within) a product with steam under pressure. Steam kills the

microorganisms by denaturing proteins within the cells. Steam sterilization is the most common method

for medical device and product sterilization because it is non-corrosive, relatively fast, and inexpensive.

Further, most healthcare facilities own one or more autoclaves on-site for reusable medical devices.

How Is Steam Sterilization Performed?

Simply speaking, contract steam sterilization is performed by steam under pressure. The most common

devices used to meet steam sterilization standards are autoclaves (pressurized vessels). Steam for

moist heat sterilization must be pure and contain no air or other non-condensable gases. Autoclaves

specialize in removing air from the chamber and replacing it with pure saturated steam. The removal of

air is critical to steam sterilization. Effective air removal depends on the availability of moisture (steam)

to displace air, the air removal system used (e.g., vacuum), the configuration of the load being sterilized,

and the absence of air leaks in the autoclave.

The basic steam sterilization cycle has three steps:

1. Preconditioning of the chamber and load within the chamber to remove air and replace it with

saturated steam

2. The chosen sterilization cycle

3. Removal of steam and release of pressure

USAGE:

autoclaves are primarily used to process laboratory media, water, pharmaceutical products, regulated

medical waste, and nonporous articles whose surfaces have direct steam contact.

What Are The Advantages And Disadvantages Of Steam Sterilization?

Steam sterilization is inexpensive, ubiquitous, and easily accessible. Further, steam sterilization is non-

toxic and sterilizes materials at lower temperatures than dry heat. Moreover, steam is penetrative and

can sterilize both inner and outer surfaces. However, steam sterilization cannot be performed on

materials that cannot withstand humidity, certain temperature levels, and vacuum pressure levels

necessary to remove air from the steam sterilization chamber. Additionally, steam can prevent the

growth of bacteria (and endotoxin production) through sterilizing products. However, steam sterilization

cannot completely destroy pyrogens on products with endotoxin contamination.

The greatest problem with sterilization by moist heat is that not all items can be exposed to pressurized

steam and maintain their integrity. Thus, sterilization by moist heat will not work for all products,

especially products containing electronics or flexible plastics. Also, oils or enclosed dry systems cannot

effectively be terminally sterilized by moist heat as steam cannot reach these items.
7. x-ray

What is X-ray Irradiation?

X-ray starts as an electron beam where electrons are generated and accelerated to gain energy.

Electrons are generated in equipment with an energy of 5 to 7.5 MeV (million electron volts) and at a

high power in the hundreds of kW (kilowatts). The electrons are then focused on a specific metal target

of high atomic number. The X-ray radiation is generated through a process called Bremsstrahlung to

create electromagnetic energy (photons) with an energy in the same range as gamma.

What is X-ray Irradiation Used for?

X-ray irradiation can effectively treat a wide variety of materials with varying densities, configurations

and orientations. Some examples of types of products processed include:

 Medical devices

 Pharmaceuticals

 Combination drug/device products

 Tissue-based and biological products

 Animal retail products

 Archives

 Cosmetics and toiletries

 Horticultural supplies

 Packaging materials

What are the Benefits of X-ray Irradiation Processing?

X-ray irradiation is safe, reliable and highly effective at treating a wide variety of products with varying

densities. The combination of shorter exposure time and improved Dose Uniformity Ratio (DUR) make

X-ray irradiation a viable processing option for a variety of products. Similar to electron beam, X-ray

processing is powered by electricity. Benefits of X-ray include:

  Improved penetration ability of photon energy, similar to gamma

 Fast and efficient targeted processing that facilitates scale from carton to full pallets of product

 Flexibility – ability to mix different products with different dose requirements in the same irradiation

cycle

 Reduced material degradation with reduced processing times and reduce of the maximal dose given

to product in comparison to Gamma and E-beam irradiation.

 Ability to process to tight dose specifications through improved DUR

 Incremental lap-based dose delivery, offering flexible and precise process definition across a wide

range of doses

Standards:

X-ray sterilization is supported by the internationally recognized consensus standard, ISO 11137, which

describes the approach to validating a dose to achieve a defined sterility assurance level (SAL).

8. plasma sterilizer

Application

Common applications for hydrogen peroxide plasma sterilizers include sterilizing the following:

 Non-hollow loads, such as electrocautery instruments, dopplers, laser probes, defibrilator paddles,

thermometers, Ophthalmic lenses, and harmonic cables

 Hollow loads, such as Laryngoscopes and their blades, shaver handpieces, fiber optic light cables, and

surgical power drills

 Endoscopes, such as rigid and flexible endoscopes.

Advantages of Hydrogen Peroxide Plasma

By using hydrogen peroxide plasma as a method of low temperature sterilization, one benefits from:
 No chemical residues

 Safety of handling

 Safety for the environment

 Short aeration time.

Disadvantages of Hydrogen Peroxide Plasma

Every type of sterilization method has its plusses and minuses. Let’s take a look at the minuses:

 Inability to sterilize: liquids, powders, and strong absorbers

 Requires specific synthetic packaging of the load

 Sterilization chamber is relatively smaller than that of an EtO sterilizer

9.Formaldehyde sterilization

Usage

Formaldehyde sterilization is used where sterilization by steam or high temperature is not possible.

Typical equipment suitable for Low-Temperature Steam Formaldehyde processing are:

 Rigid or flexible Endoscopes

 All heat-sensitive instruments for advanced eye surgery like cryo-instruments.

 Plastic materials: syringes, coils or tubing

Sterilization by LTSF
Formaldehyde is soluble in water and its inactivation power is greatly improved by the presence of

humidity. It is most commonly used as a disinfectant, but sometimes formaldehyde is used as a

sterilizing agent. The process is known as Low Temperature Steam and Formaldehyde (LTSF)

The sterilization cycle can consist of the following stages: an initial vacuum removes air from the

chamber and load, followed by steam admission to the chamber with the vacuum pump running to flush

out the air from the chamber and to heat the load, followed by a series of pulses of formaldehyde gas,

mixed with steam. Formaldehyde gas is produced by liquid formaldehyde that is passed through a

heated evaporator. Formaldehyde is removed from the sterilizer and load by repeated alternate

evacuations and flushing with steam and air. In summary, reliable sterilization using formaldehyde is
 achieved when performed with a high concentration of gas, at a temperature between 60oC and 80oC

and with a relative humidity of 75 to 100%.

Not So Welcomed Around the World

In countries such as United Kingdom, Germany, Sweden, Denmark and Norway sterilization by LSTF is

accepted, but not common. On the other hand in several countries formaldehyde as a sterilizing agent is

discouraged. LTSF has not been FDA cleared for use in healthcare facilities in the USA.

Advantages of formaldehyde steam sterilization

 Very reactive molecule, with a small difference in effectiveness between spores and cells (as is the case

with ethylene oxide EtO)

 Faster cycle time compared to EtO

 Cost per cycle is lower than EtO

 After sterilization most loads are available for immediate use

 Acts as a mutagenic agent, reacting with carbonyl, thiol, and hydroxyl groups

Disadvantages of formaldehyde gas sterilization

 The vapour is extremely irritating to the eyes

 Weak penetrating power compared to EtO

 Operates on a higher temperature than EtO

 Formaldehyde residue can remain on the sterilized goods if the rinsing phase is not 100% efficient. This

can be harmful for the patients.

 A relative humidity of ~ 75% is required in order to be effective as the gas has to dissolve in a film of

moisture surrounding the bacteria

 Not approved by FDA and only recognized in some countries

Comparison table

Comparison table between Radiation sterilization

Gamma E-beam X-ray

Photons with a
lsotropic photons; Average energy
Mode of action Electron; Typicall, 10 MeV energy direction;90%
1.25 MeV
approxima

Largest processing unit Pallets or boxes Boxes Pallets

Dose uniformity ratio Typical dose range achievable Typical minimal dose range Typical dose r

for medical device density 25-40 achievable need for medical device for medical dev

kGy; density 25-50 kGy; k

Ideal: 25-50 kGy Ideal 25-60 kGy Ideal: 2

A few kGy/h to
Dose rate A few kGy/h A few 1000 kGy/h
kG

Depends on power Typicall, Depend on po

Depend on design and cobalt activity
maximum temperature Typically, maxim
Temperature

Typically, maximum temperature can

can go to 50°C can go to
go to 45°C-50°C
Comparison table
Summary of advantages and disadvantages of commonly used sterilization technologies