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What is Sterilization Process Validation?
Sterilization Process Validation is the methodology to determine that the sterilization process will consistently achieve sterility and that it won’t have an undesirable effect on the device or its packaging. It is a technique or the process and one of the practices in health care and industries to kill and deactivate pathogenic microorganisms to maintain sterile or aseptic environment conditions.
What are the FDA’s acceptable sterilization methods?
The FDA’s most acceptable sterilization methods
Established Category A
A long history of safe and effective use is demonstrated by:
- ample literature,
- clearances of 510(k)s or approvals of PMAs
- satisfactory Quality Systems inspections
- FDA-recognized standards for development, validation, and routine control Examples of this Established Category A Sterilization Methods:
- Dry heat
- Ethylene oxide (EO) in a fixed, rigid chamber
- Moist heat or steam • Radiation (e.g., gamma, electron beam)
Established Category B
- There are no FDA-recognized dedicated consensus standards
- There is published information on development, validation, and routine control
- FDA has previously evaluated sterilization development and validation data for specific sterilizers using discrete cycle parameters and determined the validation methods to be adequate Examples of Established Category
- Sterilization Methods:
- Hydrogen peroxide (H2O2)
- Ozone (O3)
- Flexible bag systems (e.g., EO)
Novel Methods
- little or no published information,
- no history of comprehensive FDA evaluation of sterilization development and validation data through an FDA-cleared 510(k) or approved PMA for devices sterilized with such methods
- no FDA-recognized dedicated consensus standards on development, validation, and routine control.
- FDA has not reviewed and determined to be adequate to effectively sterilize the device. Examples of Novel Sterilization Methods:
- Vaporized peracetic acid
- High-intensity light or pulse light
- Microwave radiation
- Sound waves
- Ultraviolet light
What are the documents need to address in 510(k) submission?
Explain individually for ETO, Gamma, Steam, and Moist Heat.
The following are documents need to be addressed in a 510(k) submission:
⊕ For the sterilization method:
- sterilization method description
- chamber description, if not rigid (i.e., bag)
- For Established B:
- for a cleared sterilizer, 510(k) number, make, model, and cycle altered?
- if the sterilizer is not cleared, this should be stated;
- if the sterilization method has been reviewed: the 510(k)/PMA/HDE number or Device Master File containing the validation evaluation. In addition, have the cycles been altered?
- the sterilization site;
- the dose for radiation;
- for chemical sterilants, the maximum residual levels and a justification.
⊕ Validation method, and relevant standards or a comprehensive description of process/validation protocol & maybe data
⊕ Sterility assurance level (SAL) of 10-6 for devices labeled as sterile, 10-3 for devices that only contact intact skin.
⊕ Pyrogenicity Claim, if applicable: a description of the method, batch testing or sampling plan confirmation, the chosen testing limit and its justification, endotoxin units/device.
⊕ Packaging description and how it will maintain the device’s sterility, and a description of package test methods, but not package test data.
The following are documents need to be addressed in a 510(k) submission for Ethylene oxide:
⇒ sterilization method description
⇒ chamber description, if not rigid (i.e., bag)
⇒ the sterilization site;
⇒ For chemical Eto sterilants, the maximum residual levels and a justification.
⇒ Validation method, and relevant standards or a comprehensive description of process/validation protocol & maybe data
⇒ Sterility assurance level (SAL) of 10-6 for devices labeled as sterile, 10-3 for devices that only contact intact skin.
⇒ Pyrogenicity Claim, if applicable: a description of the method, batch testing or sampling plan confirmation, the chosen testing limit and its justification, endotoxin units/device.
⇒ Packaging description and how it will maintain the device’s sterility, and a description of package test methods, but not package test data.
The following are documents need to be addressed in a 510(k) submission for Gamma radiation:
⇒ sterilization method description
⇒ chamber description, if not rigid (i.e., bag)
⇒ the sterilization site;
⇒ the dose for radiation;
⇒ Validation method, and relevant standards or a comprehensive description of process/validation protocol & maybe data
⇒ Sterility assurance level (SAL) of 10-6 for devices labeled as sterile, 10-3 for devices that only contact intact skin.
The following are documents need to be addressed in a 510(k) submission for Moist Heat or steam sterilization:
⇒ sterilization method description
⇒ Validation method, and relevant standards or a comprehensive description of process/validation protocol & maybe data
⇒ Sterility assurance level (SAL) of 10-6 for devices labeled as sterile, 10-3 for devices that only contact intact skin.
The following are documents need to be addressed in a 510(k) submission For Established B:
⇒ sterilization method description
⇒ chamber description, if not rigid (i.e., bag)
⇒ For a cleared sterilizer, 510(k) number, make, model, and cycle altered
⇒ if the sterilizer is not cleared, this should be stated;
⇒ if the sterilization method has been reviewed: the 510(k)/PMA/HDE number or Device Master File containing the validation evaluation. In addition, have the cycles been altered?
⇒ the sterilization site;
⇒ for chemical sterilant, the maximum residual levels and a justification.
⇒ Validation method, and relevant standards or a comprehensive description of process/validation protocol & maybe data.
⇒ Sterility assurance level (SAL) of 10-6 for devices labeled as sterile, 10-3 for devices that only contact intact skin.
⇒ Pyrogenicity Claim, if applicable: a description of the method, batch testing or sampling plan confirmation, the chosen testing limit and its justification, endotoxin units/device.
⇒ Packaging description and how it will maintain the device’s sterility, and a description of package test methods, but not package test data.
Sterilization Process Validation and document in a 510k
Sterilization Process Validation is the methodology to determine that the sterilization process will consistently achieve sterility and that it won’t have an undesirable effect on the device or its packaging
The documentation must include:
- Device Type:
- Name of the Device
- Product code
- Regulation Number
- Common Name of the Device
- Standards
- Results and Discussion
- Conclusion
Annex:
Validation Protocol – Company Name; Common Name of the Device, Device Description Name, Methods/Process, Parameters considered, Sterilant, Dose, Acceptance Criteria
Complete Test Report – Method Employed, Parameters, D-value, F-Value, no, of cycles, Sterilant Used, Dose of radiation, VD Max, SAL etc based on type of sterilization employed. Results and Discussion and conclusion
Explain the sterilization process validation methods
Validation Methods are the processes used to confirm that the procedure or technique employed for a specific test is suitable for its intended use. Results obtained can be utilized for the determination of the quality, reliability and consistency.
The validation methods used for sterilization are as follows:
EO and Steam – Overkill or Half-Cycle Method, most of the time
Half-Cycle Method:
- The method involves estimation of the minimum time of exposure to EO, along with other process parameters except time remaining constant, at which there are no debris.
- Two further experiments should be performed to confirm the minimum time. Both should show no growth from the BIs. The specified exposure time should be at least double this minimum time.
- Method 1: Dose setting using Bioburden
- Method 2: Dose setting using Fraction Positive information.
2A: General Applications
2B: For very low bioburden
- A cycle of short duration from which debris can be recovered should also be run to demonstrate the adequacy of the recovery technique.
Sterilization validation Consensus Standards.
| Sterilization Method | Conesus Standard |
| Moist Heat (steam) | ANSI/AAMI/ISO 17665-series
Sterilization of health care products: Moist Heat – Requirements for development, validation, and routine control of a sterilization process for medical devices |
| Ethylene Oxide (rigid chamber) | ANSI/AAMI/ISO 11135
Sterilization of Health-care Products: Ethylene Oxide – Requirements for the development, validation and routine control of a sterilization process for medical devices |
| Radiation | ANSI/AAMI/ISO 11137-series
Sterilization of health care products – Radiation – Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices, and Parts-2 and -3. |
| Dry Heat | ANSI/AAMI/ISO 20857
Sterilization of health care products – Dry heat – Requirements for the development, validation and routine control of a sterilization process for medical devices (Almost) Everything Else ANSI/AAMI/ISO 14937 |
| (Almost) Everything Else | ANSI/AAMI/ISO 14937
Sterilization of Health-care Products – General requirements for characterization of a sterilizing agent and the development, validation, and routine control of a sterilization process for medical devices |
What are the sterilization process validation Methods?
The technical operation is performed as part of development, validation, or requalification to determine the presence or absence of viable microorganisms on the product or portions thereof.
Sterility testing is performed for three reasons:
- Test for sterility (USP/EP)- Confirm requirements for sterility of a product following exposure to a sterilization process or aseptic manufacture
- Test of sterility (ISO11737-2)- Qualify the minimum irradiation dose needed to achieve a specified sterility assurance level (SAL)
- Test for Sterility of Sub-lethal EO validation samples (ISO11135) to establish and prove the relationship between the BI and the natural product bioburden.
Sterility tests are carried out by:
- Direct Transfer of the product in a suitable growth medium is the preferred method according to ISO 11737-2 as the device is in direct contact with test media throughout the entire incubation period.
- Membrane Filtration after extraction of microorganisms, which is applicable for products with antimicrobial activities.
- Addition of growth medium to the product. Depending on the product, additional preparation steps may be necessary, like disassembling the device, adding surfactants to the medium, or flushing the device.
What are the labelling requirement for sterile medical devices?
Special attention should be given to the labelling of sterile devices.
- Devices that are not sterile entirely but certain parts to be sterilized must be labelled to adequately intended to be “sterile” in the package.
E.g., Caution: Only the fluid path of the set is sterile and nonpyrogenic. Do not use in a sterile or aseptic area without proper precautions.
- Devices are intended to be sterilized by the user before use. In this situation, the labelling should provide adequate information as to at least one suitable method of sterilization and any precautions or safeguards to be followed.
E.g., the labelling should describe any: unique cleaning methods required; changes in the physical characteristics of the device that may result from reprocessing, which affect its safety, effectiveness, or performance; and limit the number of times resterilization and reuse can be done without affecting the safety or effectiveness of the device.
- Single-use sterile devices, some manufacturers include labelling to advise against resterilization and reuse.
Devices are not designed or constructed to be recleaned and may not be capable of withstanding the necessary recleaning and resterilization procedures. However, where reuse is common practice, manufacturers are encouraged to provide the information.
- The label of multi-device kits or packages containing a combination of sterile and nonsterile products must not state or imply that all contents are sterile. The need for users to have instructions on how to open a sterile device package to avoid contamination of the device also needs to be evaluated. When necessary, such instructions should be included in the labelling.
- When a manufacturer modifies a device, the manufacturer must also review the labelling to ensure that it reflects current revisions and specifications.
- Some manufacturers identify labelling with a drawing number plus a revision code or date as an aid in identifying current labelling.
- The package insert or other labelling for in vitro diagnostic products is required to contain the revision date (21 CFR 809.10).
What are Established Sterilization Methods ?
FDA puts established sterilization methods into two categories,
Category A:
These methods have a long history of safe and effective use as demonstrated through multiple sources of information such as ample literature, clearances of 510(k)s, or approvals of premarket approval (PMA) applications and satisfactory QS inspections. In addition, for established methods such as dry heat, EO, steam, and radiation, there are voluntary consensus standards for development, validation, and routine control that FDA recognizes.
Examples of this Established Category A Sterilization Methods:
Dry heat
Dry heart sterilization takes longer than steam sterilization due to the inefficiencies of heating air with shallow moisture content. Compared to steam sterilization, which requires a temperature of of around 121 degrees Celsius to be maintained for approximately 30 minutes, dry heat sterilization requires higher temperatures of around 180 degrees Celsius to be effective at neutralizing biological contaminants and their spores.
For this reason, dry heat sterilization is most appropriate for medical devices that are heat resistant but susceptible to water damage, making steam sterilization a poor choice. Hot air ovens are the most common setup for dry heat sterilization of tools composed of metal or glass.
EO with devices in a fixed, rigid chamber
Ethylene oxide sterilization is a chemical method that is popular among medical device manufacturers. Unlike steam sterilization and dry heat sterilization, which require that the medical device be heat stable, a variety of materials – like plastics and electronic components – can be exposed to ethylene oxide gas without distorting the medical device’s form or ability to function.
As an alkaline agent, ethylene oxide gas reacts with DNA, proteins, and enzymes to disrupt cell growth and division, thereby killing the microorganism. In addition to penetrating small spaces inside medical devices, ethylene oxide can also be used to sterilize medical devices that have already been packaged in plastic.
However, this medical device sterilization method has its drawbacks; for one, ethylene oxide gas is toxic to humans and highly reactive at low temperatures, making it imperative that the sterilization procedure take place in a leak-proof chamber. In addition, the method is more complex than other forms of sterilization as it requires three steps to complete. First, devices are prepared for sterilization through environmental controls, then, the operator sterilizes the device by adding the gas, and finally, the gas is thoroughly removed from the product.
Moist heat or steam
Characterized by high temperatures and pressures, steam sterilization is most appropriate for devices composed of stable, heat-resistant materials such as steel. In addition, reusable surgical tools are often steam sterilized in an autoclave to kill any microorganisms that may be present on the surface of the instruments, as well as bacterial spores, which can be resistant to other forms of disinfection.
Despite its ability to sterilize equipment quickly, steam sterilization is often not the decontamination method of choice for medical device manufacturers. While the steam sterilization process takes just three to 15 minutes, medical instruments must be allowed to cool and dry completely over several hours before being used.* The build-up of water droplets inside device components can impair their functioning and corrode materials that aren’t meant to come into contact with water. Of course, plastic and electronic components can also be damaged by exposure to steam, making this sterilization method unsuitable for most complex medical devices.
Radiation (e.g., gamma, electron beam)
Sterilization of medical devices using radiation does not leave any trace of radioactivity. Therefore, irradiating medical devices using gamma or electron beam (E-beam) radiation is a clean way to sterilize.
Like ethylene oxide sterilization, radiation can penetrate product packaging. However, the latter is a less time-consuming method. In addition, dense materials can also be irradiated quite efficiently.
This sterilization technique is best-suited to single-use devices like implants, catheters and syringes. When used to sterilize reusable devices, processors will need to perform quarterly dose audits to ensure that the level of radiation exposure is sufficient to destroy any microorganisms on the device.
This sterilization method causes slight fluctuation in temperature, making it appropriate for use on devices made from heat-sensitive plastics and other materials. For example, autoinjectors like the EpiPen, pre-filled syringes and other disposable medical devices can be sterilized using this method. However, care must be taken when using this method as it can cause cosmetic and functional issues such as discolouration and harmful effects on various materials used in the device.
Category B:
There are other established methods for which there are no FDA-recognized dedicated consensus standards but for which published information on development, validation, and routine control is available.
Examples of these Established Category B Sterilization Methods:
Hydrogen peroxide (H2O2)
Hydrogen peroxide sterilization is a low-temperature sterilization process that utilizes hydrogen peroxide vapour. The vapour fills the sterilization chamber, penetrates the device, and sterilizes exposed surfaces. Hydrogen peroxide sterilization is one of the few commonly used low-temperature sterilization modalities, making it an option for sterilization of heat-sensitive devices. Hydrogen peroxide sterilization has cycle times typically running less than an hour. Hydrogen peroxide is compatible with a wide range of materials commonly used for medical devices. Hydrogen peroxide sterilizers must adhere to OSHA’s Permissible Exposure Limit (PEL), which is one ppm over 8 hours. Since these systems are self-contained, exposure to workers is limited. The only byproducts of the process are water and oxygen.
Ozone (O3)
Ozone has been used for years as a drinking water disinfectant. Ozone is produced when O2 is energized and split into two monatomic (O1) molecules. The monatomic oxygen molecules then collide with O2 molecules to form ozone, which is O3. Thus, ozone consists of O2 with a loosely bonded third oxygen atom that is readily available to attach to and oxidize other molecules. This additional oxygen atom makes ozone a powerful oxidant that destroys microorganisms but is highly unstable (i.e., the half-life of 22 minutes at room temperature).
Flexible bag systems (e.g., EO in a flexible bag system, diffusion method, injection method)
Contact Us For sterilization process validation
The FDA 510k quality is important for quick approval and less review comments. The development of an FDA 510(k) file is difficult due to 17 different modules to satisfy each 510(k) need. All pertinent procedures, test results, and other supporting documentation are offered in the designated annexures with the proper file numbering and titles. The majority of 510(k)s have far more than 250 pages. Write to us or submit the online quote request form.
QSR requirements for validating reprocessing methods
FDA Quality System Regulation (QSR) requires manufacturers of Class II and III as well as some Class I devices to develop and maintain procedures for process validation by defined user needs and intended use. For devices affected by the new reprocessing guidance, US regulators expect manufacturers to comply with components of 21 CFR Part 820 addressing reprocessing instructions for reusable devices.
Even though many reusable devices are exempt from the 510(k) clearance review, these must still comply with QSR requirements for proper labeling instructions for reprocessing, according to the guidance.
What are reusable medical devices? What are the end users cleaning process?
Reusable medical devices are devices that health care providers can reprocess and reuse on multiple patients. Examples of reusable medical devices include surgical forceps, endoscopes, and stethoscopes.
All reusable medical devices can be grouped into one of three categories according to the degree of risk of infection associated with the use of the device:
• Critical devices, such as surgical forceps, come in contact with blood or normally sterile tissue.
• Semi-critical devices, such as endoscopes, come in contact with mucus membranes.
• Non-critical devices, such as stethoscopes, come in contact with unbroken skin.
In general, reprocessing reusable medical devices involves three steps:
1. At the point of use, such as in the operating room, devices receive initial decontamination and cleaning, and steps are taken to prevent the drying of blood, tissue, other biological debris, and contaminants on the device.
2. The device is then transferred to the reprocessing work area where it is thoroughly cleaned.
3. Finally, the device is either disinfected or sterilized, depending on the intended use of the device, and the materials from which it is made, and it is stored or routed back into use.
Cleaning is the physical removal of soil and contaminants; the methods and agents used for cleaning should be designed to remove such soil and contamination effectively.
Effective cleaning should:
• minimize the soil transfer from one patient to another or between uses in a single patient;
• prevent accumulation of residual soil throughout the product’s useful life; and
• Allow for successful, subsequent disinfection/sterilization steps.
The end-user cleaning process can be manual, automated, or a combination of the two.
Basic Components of Cleaning Solutions
Water is the most common solvent on earth and provides the base for most cleaning solutions. The detergent helps to loosen debris from surfaces. The detergent then acts to hold the debris in suspension, preventing it from re-depositing on the device and allowing it to be easily rinsed away.
Surfactants increase cleaning efficacy by reducing surface tension thus allowing for better penetration of the soil.
Buffers provide better compatibility with materials and inhibit corrosion.
Chelating agents assist in reducing the potential negative effects of hard water that may be used when diluting the solution. They also bind with hard water minerals to prevent them from depositing on the device or adversely reacting with the cleaning solution. It is important to note that hard water may cause spotting or leave deposits on the device.
Enzymes increase cleaning efficacy, speed the cleaning process and help to minimize the need for manual brushing and scrubbing. There are a variety of enzymes available, each targeting a particular type of soil. The most common enzyme found in solutions used for cleaning medical devices is a protease, which helps to break down protein-based soils such as blood and feces. Also available are amylase to break down starches like those found in muscle tissue, cellulase to break down carbohydrates like those found in connective fluid and joint tissue, and lipase to break down fats like those found in adipose tissue. Any combination of these enzymes may be present in a solution. Solutions containing enzymes can often be used at a more neutral pH and lower temperatures than those without enzymes.
Explain FDA’s Six Criteria for Reprocessing Instructions.
Six criteria that should be addressed in the instructions for use with every reusable device to ensure users understand and correctly follow the reprocessing instructions:
• Labeling should reflect the intended use of the device.
It should include reprocessing instructions appropriate for its design, intended use, and likely exposure to contaminants.
• Reprocessing instructions for reusable devices should advise users to thoroughly clean the device.
All reprocessing instructions should recommend a “thorough” cleaning of a device. If necessary, device disassembly instructions should be included if taking a product apart is required to thoroughly clean it.
• Reprocessing instructions should indicate the appropriate microbicidal process for the device.
Processes should reflect up-to-date infection control principles including the Spaulding Classification system, as well.
• Reprocessing instructions should be technically feasible and include only devices and accessories that are legally marketed.
Instructions should be technically feasible in the context of their intended locations; any equipment necessary for proper sterilization of the device should be readily available to the product’s intended user.
• Reprocessing instructions should be comprehensive.
Any special accessories, disassembly and reassembly, and cleaning methods necessary for proper reprocessing should be included.
• Reprocessing instructions should be understandable.
FDA criteria are direct, but important to keep in mind while developing reprocessing IFU (Instructions for use). Developing these instructions is the first step in preparation for reprocessing validation. The general flow of reprocessing includes a pre-cleaning step, followed by either disinfection or sterilization. Important items to consider while developing reprocessing IFU include the type of detergents, disinfectants, or sterilization processes, device design challenge points (stickers, lumens, seams, etc.), and reprocessing accessories (if applicable).
What is a pyrogenicity claim: Is the test method identified?
A request or demand for pyrogen testing to be provided in the submission of a product or device to the US market is known as a pyrogenicity claim. Yes, it is identified.
As per 2016 guidance, the FDA stated that devices falling into the following categories should meet pyrogen limit specifications:
1. implants;
2. devices in contact directly or indirectly with the cardiovascular system, the lymphatic system, or cerebrospinal fluid, including devices that are present for similar systemic exposure; or
3. devices labeled “non-pyrogenic.”
Is there any specific packaging requirement for sterile medical devices?
• ISO 11607-1 defines requirements for sterile barrier system materials selection and their design and testing.
• ISO 11607-2 defines manufacturing packaging process validation requirements for forming, sealing, and assembly processes.
Developing packaging system requirements - specify the customer’s design needs for the sterile barrier and the protective packaging system.
Medical device manufacturers must obtain customer feedback on the package ease-ofuse and gain a solid understanding of the storage, transportation, and shelf life requirements of the device.
Other considerations include the requirements for the microbial barrier and evaluating possible interactions with the sterilization method on both the sterile barrier as well as the device itself.
Designing a sterile barrier . Examples of these include porous and nonporous pouches, header, patch bags, and thermoformed trays. The packaging solution is a direct result of the system requirements.
Designing protective packaging to ensure the device can survive transportation stresses from the point of manufacture to the customer. One of the most common causes of packaging failures is not considering how products are shipped to customers. For example, palletized products from the manufacturer must be tested to ensure they can be delivered through sterilization, but further testing is required if those pallets are broken down and the product is shipped to customers through common carriers. Having a box thrown into a UPS truck is not the same as shipping a skid from the manufacturer. One of the most common mistakes we see is not considering consolidated shipping configurations that are used for sterilization. Orthopedic implants, in particular, generate significant stresses on packaging and are highly sensitive to shipping configurations.
Package prototyping is recommended to ensure the final package will meet the needs of the customer and will be manufacturable and optimized for final assembly of the device. Selecting a contract manufacturer with internal thermoforming and a broad array of packaging technologies can provide companies with a realistic sample of the final package much faster than having to coordinate multiple suppliers.
Package verification testing is a critical step and often overlooked, which increases the chance that the package fails the final transit test. The final version of the product is packaged and it undergoes preliminary package testing to ensure a high probability of passing the final transit testing. Some labs report up to 30% of their medical device packages fail the ASTM or ISTA transit tests.
A preliminary transit test greatly reduces this risk. Typical sterile package verification tests include peel testing and bubble leak testing. These tests are to be validated in advance.
A sterile presentation test : It must be conducted with actual end-users to ensure the medical device can be aseptically presented. Scrub nurse and doctor interaction with the package is critical. Some packages can be designed to deliver the device to the sterile field by allowing the device to gently “fall” out of the package onto a sterile table. Other devices require the product to hold over the sterile field while the scrub nurse manually removes the device from the package. Each of these scenarios influences the design of the package regarding ease of opening and, for thermoformed trays, how the package designed to be held with one hand while peeling the lid with the other.
What are Novel Sterilization Methods? Explain
• little or no published information,
• no history of comprehensive FDA evaluation of sterilization development and validation data through an FDA-cleared 510(k) or approved PMA for devices sterilized with such methods
• no FDA-recognized dedicated consensus standards on development, validation, and routine control. FDA has not reviewed and determined to be adequate to effectively sterilize the device.
• Examples of Novel Sterilization Methods:
• Vaporized peracetic acid
Peracetic acid (PAA) is formed by the reaction of acetic acid and hydrogen peroxide (H2O2); these compounds exist in equilibrium and their eventual decomposition results in oxygen (O2), carbon dioxide (CO2) and water (H2O). Liquid peracetic acid (PAA) and vaporized peracetic acid (VPA) are highly biocidal sterilants that maintain efficacy in the presence of organic soil while removing surface contaminants. VPA’s non-toxic, sterile processing solution leaves behind no harmful residuals, providing not only a safer work environment for employees but a safer product for patients. With VPA breaking down into carbon dioxide, oxygen and water, the VPA process is noncarcinogenic, nonexplosive/flammable, and requires no external ventilation. It can be integrated directly into the on-site manufacturing process, reducing transportation and inventory costs associated with other contract sterilization methods.
Sterilization process time can vary greatly, depending upon the product being sterilized and including the pre-sterilization and post-sterilization aeration periods and external quality processes. Because it requires no pre- or post-aeration, VPA can significantly reduce the overall process time and reduce inventory costs. It also provides the option to bring sterilization on-site, eliminating the inefficiencies associated with off-site sterilization.
• High intensity light or pulse light
A method and apparatus for terminal sterilization. The method orients a wall of a container in relation to at least one flashlamp, where the wall has an inner surface and an outer surface. The method creates a vortex in a fluid held by the container. The method generates from each flashlamp at least one pulse of high-intensity light in a broad spectrum and exposes the container to each pulse of high-intensity light.
• Microwave radiation
Microwaves are radio-frequency waves, which are usually used at a frequency of 2450 MHz. The microwaves produce friction of water molecules in an alternating electrical field. The intermolecular friction derived from the vibrations generates heat and some authors believe that the effect of microwaves depends on the heat produced while others postulate a nonthermal lethal effect. The initial reports showed microwaves to be an effective microbicide.
• Sound waves
The most common type of mechanical automatic cleaner is the ultrasonic cleaner. Ultrasonic cleaners are used in conjunction with detergents and enzymatic cleaners. Ultrasonic cleaning removes particulates by cavitation (bubbles) and implosion.
• Ultraviolet light
UV radiation can significantly affect the normal state of life by inducing single as well as double DNA strand breaks. When significant double DNA strand breaks occur, it can lead to the loss of genetic material [26]. The effectiveness of UV radiation in sterilization applications is dependent on the wavelength of UV light. The maximum absorption for DNA and RNA occurs at a wavelength of 260 nm and therefore, exposure to UV light around 260 nm wavelength is desired
List the specific Guidance and standards for sterilization process.
https://www.fda.gov/media/141277/download
ANSI/AAMI/ISO 17665-series
Sterilization of health care products: Moist Heat - Requirements for development, validation, and routine control of a sterilization process for medical devices
ANSI/AAMI/ISO 11135
Sterilization of Health-care Products: Ethylene Oxide – Requirements for the development, validation, and routine control of a sterilization process for medical devices
ANSI/AAMI/ISO 11137-series
Sterilization of health care products – Radiation – Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices, and Parts 2 and -3
ANSI/AAMI/ISO 20857
Sterilization of health care products - Dry heat - Requirements for the development, validation, and routine control of a sterilization process for medical devices