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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

VALIDATION PROTOCOL OF ETHYLENE OXIDE STERILIZATION PROCESS

Company Name

Eto Sterilizer manufacturer name: Date of Purchasing: Date of Installation: Model number: Capacity: Operator Name: Department (Place)

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Table of Contents

PROTOCOL APPROVAL SHEET..................................................................................................3 REVISION HISTORY.....................................................................................................................3 OBJECTIVE:-...................................................................................................................................4 SCOPE:- ..........................................................................................................................................4 RESPONSIBILITY:-........................................................................................................................4 STANDARDS FOR REGULATORY REQUIREMENT:-.............................................................4 LIST OF DOCUMENTS:-...............................................................................................................5 PRE-REQUISITE:-...........................................................................................................................5 Process and Validation Approach:-..................................................................................................7
Process Validation Procedure:-.................................................................................8

Sampling method and test method:-...............................................................................................13


LIST OF TEST TO BE EXECUTED..............................................................................13

Appendix 1 Simulation of Anticipated Process Conditions...........................................................20 Appendix 2:- Determination of Bioburden ..................................................................................21 Appendix 3(GLOSSARY)..............................................................................................................22

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

PROTOCOL APPROVAL SHEET The Validation Protocol shall be Prepared, Reviewed and Approved by the concerned personnel. It shall be signed and dated as shown below. Prepared by: NAME DESIGNATION Assistant manager- QA(validation) SIGNATURE DATE

Checked by: NAME DESIGNATION SIGNATURE DATE

Approved by: NAME DESIGNATION SIGNATURE DATE

REVISION HISTORY REVISION 01 REVISION DATE REASON FOR REVISION/CHANGE REVISED BY REQUEST Original release

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

OBJECTIVE:To determine that Ethylene oxide sterilization process consistently performs as intended by running the system and recording all relevant information. The Data and Test results must demonstrate that the process meets pre-determined specifications under normal conditions as well as worst case conditions. SCOPE:The scope of validation protocol is to provide sterilization validation strategies for ethylene oxide sterilization of medical device. This document will show two approaches for reducing or eliminating bioburden on medical devices. This will also show test method, sampling method and acceptance criteria used in validating ethylene oxide sterilization of medical devices. RESPONSIBILITY:Person Validation team Responsibility Preparation of protocol Organization of validation activity Collecting the samples and sending to QC Review and interpretation of final results Preparation of report Quality control Review of protocol and report Analyzing the test samples Reporting and interpretation of results Production Review of protocol and report Conducting the validation activity as per the protocol Quality assurance manager Review and approve the validation protocol

STANDARDS FOR REGULATORY REQUIREMENT: ISO 11135-1:2007, Sterilization of health care products- Ethylene oxide- Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices ISO 10993-7, Biological evaluation of medical devices- Part 7: Ethylene oxide sterilization residuals ISO 11737-1, Sterilization of medical devices Microbiological methods Part 1: Determination of a population of microorganisms on products

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

ISO 11737-2, Sterilization of medical devices Microbiological methods Part 2: Tests of sterility performed in the validation of a sterilization process ISO 10993-1:2002, Biological evaluation of medical devices Part 1: Evaluation and testing

LIST OF DOCUMENTS: SOP for ethylene oxide sterilization process SOP for environmental monitoring SOP for sampling procedure SOP for testing method SOP for material handling including biological indicator Sterilization cycle parameter specification sheet

PRE-REQUISITE:The following requisite must be fulfilled before the ethylene oxide sterilization process validation. Equipment qualification:Equipment associated with ethylene oxide sterilization process must be qualified prior to process qualification. Calibration: - All process sensing, controlling, indicating, and recording devices on the sterilizer or independent systems associated with sterilizer must be calibrated and recoded. Calibration program must be documented and detailed procedure of calibration frequency for all the instruments should be identified. Product qualification:Product and packaging material evaluation: - As per ISO 11135 product and packaging material must be evaluated for ethylene oxide and humidity penetration. Product grouping: - For efficient and cost effective performance validation similar device can be grouped in to families. A family of products can be considered to be all those products of similar design and material of construction, similar bioburden levels but can be consist of different sizes. Devices can be grouped based on several criteria: Page 5 Similarity of materials of construction Same product design of different sizes, lengths or thickness

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Design complexity Similar method of manufacture Multiple combinations of devices Amount and type of packaging

Selection of family representative: - Each family of products will contain a number of devices. From these devices, the representative challenge product is selected. The selected device will present a greater challenge to the sterilization process and will be the most difficult to sterilize device in the family group and will be used as the BI carrier. Following criteria can be used to select the family representative: Longest tubing with the smallest lumen The highest bioburden Smallest opening into the interior of a device Most subassemblies, Most convoluted passageways Most dense package configuration

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Process and Validation Approach:Parameters to be Verified

Bioburden Assessment

No. of microorganism on product Loading Pattern 1. Temperature of Load 2. Humidity of Load

Loading in chamber Environmental Preconditioning

Initial Evacuation

1. Evacuation rate 2. Number of nitrogen wash 1. Humidity of load

Humidification

2. Temperature of load 1. Gas injection rate 2. Gas Concentration 3. Duration of Exposure

Gas injection and Gas dwell

Post exposure gas purge and air in bleed Heated Aeration Page 7

1. Vacuum rate 2. Number of Nitrogen wash 1. Temperature 2. Aeration time

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Process Validation Procedure:Bioburden assessment: - An understanding of the population of viable microorganisms on a finished device (bioburden) is necessary and required to support the validation process. The bioburden assessment includes the total number of microorganisms with their identities. The identification needs confirmation of gram stain characteristics and genus. It provides useful information and can be used to monitor changes over time and as a comparison to organisms recovered during environmental monitoring. For determination of bioburden Refer to Appendix 2

Selection of Process Challenge Device (PCD):- Process challenge device can be selected from the family representatives in order to reduce the number of products tested during the validation. Internal PCD is the most difficult to sterilize device seeded with a BI. For ease of sample removal an external PCD can be used in the validation. External PCDs are the external BI test pack that replaces the internal PCD. External PCD should serves as a resistance greater than or equal to that of the internal PCD. The external PCD is usually placed on the outside of the sterilization load between cases, just inside the case or under the stretch wrap.

BI or PCD placement in the product load: - After the product load challenge has been identified, the BI or PCD positioning and placement can be determined. BIs and PCDs should be distributed throughout the product load and, as much as possible, in the same orientation (e.g., vertical).

Following minimum number of BIs/PCDs to be included in each validation cycle (as per ISO 11135-1: 2007): Up to 10 m3, the number of BIs is m3, with a minimum of 5. From 10 m3 up to 100 m3, the number of additional BIs is one per additional cubic meter.

Temperature and Humidity sensor in product load: - For humidity check in preconditioning and conditioning/sterilization one humidity sensor per 2.5 m3, with minimum number of sensor is two should be placed in sterilization load and it should include pallet centers, edges and surfaces. Page 8

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

For temperature monitoring in validation one temperature sensor per cubic meter of product volume with a minimum of 3 sensors should be placed in the load. Load Temperature: - ISO 11135-1:2007 requires that the minimum temperature of product permitted to enter preconditioning be determined. Load temperature prior to entrance to preconditioning should be determined at the lowest temperature zone. Direct placement of cold loads into preconditioning can result in excessive water condensation and load wetting, which can cause product damage and reduced lethality. In process validation it requires to simulate the worst condition to which the load will ever be exposed. The anticipated load temperature extremes can be simulated during validation by following techniques described in the appendices 1. Identification of the worst case location or cold spot: - temperature is the easiest variable to measure and monitor, therefore temperature is used as an indicator of the worst case location in the sterilization load. During the preconditioning or conditioning phase temperature profile against time of the sterilization load measured and based on that data the worst case location or cold spot is identified.

Process Qualification Runs:-

For validation, a microbial challenge will be performed to demonstrate the adequacy of the process to achieve the desired Sterility Assurance Level. Two methods are used a) Half cycle method (Overkill approach) b) Bioburden / BI method

a) Half Cycle Method: - During the bioburden assessment, if characterization of bioburden is not performed and the bioburden level is more than 100 CFU than the following steps are performed. In this method one fraction cycle, 3 one-half cycle and one full cycle is performed.

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Place Biological Indicator (BI) with 10 spores of Bacillus atropheus in the PCDs and product samples in each pallet with humidity and temperature sensor. (Place PCDs to cold spot of the product load)

Load pallets of sterilization load in to the sterilization chamber

Run fractional cycle according to prescribed cycle parameter (Use or gas exposure time than full cycle)

Aerate the product

Remove the product sample and PCDs from the load

Perform sterility test on product sample and BIs. Additionally perform Bacteriostasis/Fungi stasis test on the product sample.

If product sterility samples show survival, repeat the run on new load with elevated gas exposure time until no survival in product and growth in BI (evaluation of BI appropriateness)

Run 3 consecutive half cycle according to prescribed cycle parameter (Use gas exposure time than full cycle) Aerate the load

Remove the product sample and PCDs and perform sterility test on product sample and BIs

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Sterility test should show no growth for both product and BIs samples

Perform one full cycle (routine process exposure time) on the aerated sterilization load. Place addition product sample for the additional test.

Aerate the load

Remove the product sample and PCDs Perform following test on product sample 1. LAL test (pyrogen test) 2. Product and packaging functionality test 3. Biocompatibility test 4. Ethylene oxide residue test b) Bioburden /BI method: - This method requires that bioburden level be demonstrated to be relatively consistent over time and the resistance of the bioburden be shown to be equal to, or less resistant than, the resistance of the biological indicator. During the bioburden assessment, if the characterization of bioburden performed and level of bioburden is less than or equal to 100 CFU which indicating a lesser challenge than the BI than the following steps can be followed. Establish worst case location in the product load based on temperature distribution and humidity of load

Place BI with known amount of microorganism in the PCDs, temperature and humidity sensor

Perform 5 fractional cycles with graded exposure time (e.g. 0, 4, 8, 12, 16 minutes) Aerate the load

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Perform sterility test on BI

Calculate rate of inactivation (D value) using survival curve or fractional negative method

Calculate half cycle and full cycle exposure time

Place product sample and PCDs in each pallet with temperature and humidity sensor

Run 3 half cycle according to prescribed cycle parameter Aeration Remove product sample and PCDs. Perform sterility test on product sample and BIs. Additionally perform fungi stasis/ Bacteriostasis test.

Perform one full cycle (routine process exposure time) on the aerated sterilization load. Place addition product sample for the additional test.

Aerate the load and remove the product sample and PCDs

Perform following test on product sample 1. LAL test (pyrogen test) 2. Product and packaging functionality test 3. Biocompatibility test 4. Ethylene oxide residue test Page 12

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Maintainace of Validation:Requalification: 1. Any significant change in product, manufacturing process, packaging, sterilization equipment or process, product loading or density may necessitate requalification. A documented formal review of any change should be undertaken to make this determination. 2. To ensure continued control, periodic repetition (annually is recommended) of all or part of the performance validation should be considered.

Sampling method and test method: Sampling method:Sample taken for validating sterilization process should be representative of entire batch and it should be taken from most critical part of load configuration. Sample must be taken from each separate packaging system place on. References AS ISO 11737:1 and ISO 11737:3 AS ISO 11737:2

LIST OF TEST TO BE EXECUTED No Test Objective 1 Bioburden To check the liable micro determination organism in the product. 2 Sterility testing Product Sterility Testing is determine any viable microorganisms remain on product during sterilization 3 Biological Indicator To challenge the sterilization Testing process and are used during validation and routine processing. 4 Fungi stasis/ Bacteriostasis LAL test Product package functionality test Product functionality test To determine the recovery percentage, microbial growth and will be used to correct Bioburden results. To determine Endotoxin level (pyrogen-end product of gram negative bacteria) To evaluate the outer packaging of a device.

ISO11139:2006

AS ISO 11737:1

5 6 7

TGO NO. 50, USP (161) & (85) ISO 11607-1

To evaluate the changes in the ISO 11607-1 product characteristic.

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Biocompatibility o Cytotoxicity test o Biodegradation test o Carcinogenicity test o Sensitization test o Irritation test Ethylene oxide residue test

Biocompatibility testing is ensure ISO 10993-1- 9 to 12 that sterile devices are compatible with biological systems

To ensure the amount of ethylene ISO 10993-7 oxide residual levels are within limits.

1. Test result and acceptances criteria:No. 1 2 Test Sterility Testing Biological Indicator Sterility Testing Acceptance criteria No Growth for product sample Fractional cycles: No growth Half Cycles: No growth Full Cycles: No growth All positive controls must show growth 3 4 5 6 Fungi stasis/ Bacteriostasis LAL test Product Package Functionality Test Product Functionality Test Biocompatibility Test Must be negative Endotoxin and pyrogen must be absent Packaging integrity must be intact Product should not show degradation, discoloration physical changes Product must be biocompatible any and Test results

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

8 9

Ethylene Residue Test

Oxide

Ethylene oxide residue levels must be in limit at the day of release All parameter must meet specified cycle parameters with

Process parameters

2. Process parameter check steps:Environmental preconditioning: Parameters to be checked Temperature of preconditioning room Humidity of the preconditioning room Duration of preconditioning Actual Specification

Acceptance Criteria met [yes]/ [no] Comments:

Verified by: _____________________ Initial evacuation: Point of consideration The evacuation rate(vacuum) to maintain the seal integrity Amount of negative pressure Number of Nitrogen wash Actual

Date: ________________________

Specification

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Acceptance Criteria met [yes]/ [no] Comments:

Verified by: _____________________ Humidification: Point of consideration Level of moisture Heat Actual

Date: ________________________

Specification

Acceptance Criteria met [yes]/ [no] Comments:

Verified by: _____________________ Gas injection and gas dwell: Point of consideration Gas concentration Duration of exposure Actual

Date: ________________________

Specification

Acceptance Criteria met [yes]/ [no] Comments: Page 16

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Verified by: _____________________ Post exposure gas purge and air in bleed: Point of consideration Number of Nitrogen wash Vacuum rate Actual

Date: ________________________

Specification

Acceptance Criteria met [yes]/ [no] Comments:

Verified by: _____________________

Date: ________________________

Heated aeration: Point of consideration Temperature of room Aeration duration Actual Specification

Acceptance Criteria met [yes]/ [no] Comments:

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Verified by: _____________________

Date: ________________________

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Appendix 1 Simulation of Anticipated Process Conditions Anticipated load temperature extremes during transport, handling, and storage can be simulated by following techniques:a) Use of cold storageFor example, the product load is stored under refrigeration or deliberately induced cold temperature. The temperature of the storage area should be less than or equal to the lowest temperature the product is expected to be exposed to throughout the year. Product temperature data are recorded during the storage time. The time in storage should be equal to or greater than the maximum time any product load is expected to exist under such conditions, or the maximum product temperature while in storage becomes the minimum acceptable product temperature for a load to be admitted to the preconditioning phase. This applies to preconditioning or to conditioning when preconditioning is not used. The use of refrigeration can result in unrealistically low humidity levels, with the resultant desiccation of the load. A desiccated load can be much more difficult to sterilize than a non-desiccated load. b) Temperature modelingData analysis of load temperature studies may be augmented by modeling to establish the additional time required for starting temperatures lower than those studied. If lower starting temperatures are allowed, the effect of additional condensation should be evaluated. For example, at the time of validation, the lowest product load temperature point is 60 F prior to entering preconditioning. Once in preconditioning, data yield a temperature profile for the worst-case position showing that the load temperature increases to 100 F by the end of preconditioning. When the temperatures over time data are graphed, the linear part of the time/temperature relationship (which is generally the initial few hours of preconditioning when the difference between load temperature and preconditioning area temperature is the greatest) can be used to extrapolate the necessary preconditioning times for sterilization loads at temperatures lower than 60 F. Using this technique to calculate a minimum preconditioning time will yield a time that is greater than that actually required. Other techniques of temperature modeling can be used. c) Seasonal validationpreconditioning validation can target those seasons that present the most extreme temperature and humidity conditions. For example, a validation conducted during the coldest part of the year (which would also present the lowest ambient humidity level) could yield minimum preconditioning parameters valid for routine production cycles during the entire year. However, in cases of validations performed during the summer, it is advisable to validate the preconditioning process with simulated cold storage, mathematical modeling or to repeat the preconditioning validation at least once during the winter to confirm the validity of the parameters.

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Appendix 2:- Determination of Bioburden Determination of Bioburden: Procure ten (10) each product samples randomly from three (3) different batches of routine production processes. Send to approved test lab for bioburden evaluation (enumeration of aerobes, fungus, and spores.) At the test lab, perform the bioburden determinations using a standard method as outlined in IS0 1 1737-1 by extracting each device individually and filtering the extract through a sterile bacterial retentive filter. A validation of bioburden recovery should be performed. (An additional five non sterile samples are required.) Determine the average bioburden per device for each lot, as well as the overall batch average bioburden Calculate the overall average bioburden. If a spike (a single value at least 2 X the overall average) occurs, the spike value may be used rather than the average for the cycle selection. Sample item portion (SIP) method for bioburden determination: Based on following criteria product sample portion determined for bioburden assessment. 1) If the product with an average Bioburden equal to or greater than 1.0 whenever practicable, an entire product (SIP equal to 1.0) should be used for testing in accordance with ISO 11137:2. When the use of an entire product is not practicable, a selected portion of product (sample item portion) may be substituted. The SIP should be as large a portion of item as practicable in order to manipulate in the laboratory, and should be of a size that can be handled during testing. 2) If a product with an average Bioburden equal to or less than 0.9, an entire product (SIP equal to 1.0) shall be used for testing in accordance with ISO 11137:2. 3) If the Bioburden is evenly distributed on and/or in the item, the SIP may be selected from any portion of the item. If the Bioburden is not evenly distributed, the SIP shall consist of portions of product selected at random, which proportionally represent each of the materials from which the product is made. If the Bioburden distribution is known, the SIP may be selected from the portion of the product that is considered to be the most severe challenge to the sterilization process. The value of SIP can be calculated on the basis of length, mass, volume or surface area Basis for SIP Product Length Mass Tubing (consistent diameter) Powders Gowns Implants (absorbable) Fluid Implants (non-absorbable) Tubing (variable diameter)

Volume Surface area

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TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Appendix 3(GLOSSARY) ETHYLENE OXIDE STERILIZATION GLOSSARY Below is an alphabetical list of terms that may be used in discussions of ethylene oxide (EO) sterilization as recognized by medical device manufacturers inspected by the U.S. FDA. All definitions or explanations are to be taken as applied specifically in the context of EO sterilization processing. Aeration Part of the sterilization process during which ethylene oxide and/ or its reaction products desorb (outgas) from the medical device until predetermined levels are reached. This may be performed within the sterilizer and/or in a separate chamber or room. Aeration Area Either a chamber or a room in which aeration occurs. The temperature in the aeration area is elevated and controlled to assure that the aeration process is accelerated and repeatable. Air is recirculated in the room to maintain good heat distribution with a portion of the air stripped off and cleansed with the pollution control equipment. The stripping of the air reduces the amount of free ethylene oxide resident in the rooms, thus prevents recontamination of product load. AAMI Abbreviation for the Association for the Advancement of Medical Instrumentation. AAMI generates guidelines which are used in the industry for validating, monitoring, and performing routine EO sterilization processes. ANSI/AAMI/ISO 11135:2007 International Organization for Standardization (ISO) Guidance document which has been adopted and published by AMI (and ANSI) to address validation and routine control of ethylene oxide sterilization. Bacteriostasis/Fungi stasis Test Test performed to evaluate the presence of microbial growth inhibiting properties of a health care product. This test assures that any reaction of the growth medium with the different materials used in the manufacture of the device will not mask or prevent growth from any viable organism remaining on the device after being subjected to a sterilization process. Bioburden Population of viable microorganisms on a raw material, component, finished product, and/or package. Unlike the gamma irradiation process, bioburden data is not utilized in ethylene oxide sterilization to determine the sterilization process. It is collected to quantify the amount of product contamination, which is then compared to the population of the biological indicator used in the EO sterilization process. Biological Indicator Inoculated carrier contained within its primary pack ready for use and providing a defined resistance to the specified sterilization process. Calibration Comparison of a measurement system or device of unknown accuracy to a measurement system or device of known accuracy (traceable to national standards) to detect, correlate, report, or eliminate by adjustment, any variation from the required performance limits of the unverified measurement system or device. All critical measuring devices utilized on ethylene oxide sterilizers which may impact the quality of the process are calibrated to traceable national Page 22

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

or international standards. Chamber Enclosed area which only accommodates sufficient product to fill the sterilizer. EO chambers are constructed of steel or stainless steel and are designed to withstand the extreme pressures and elevated temperatures utilized in the EO sterilization process. Commissioning Obtaining and documenting evidence that equipment has been provided and installed in accordance with its specification and that it functions within predetermined limits when operated in accordance with operational instructions. All EO sterilization equipment which complies with ANSI/AAMI/ISO 11135 is commissioned. Conditioning Treatment of product within the sterilization cycle, but prior to sterilant admission, to attain a predetermined temperature and relative humidity. This part of the sterilization process may be carried out either at atmospheric pressure or under vacuum (see also preconditioning). Critical Parameters Parameters identified as being essential to the sterilization process and requiring monitoring. D-Value Time (expressed in minutes) required to achieve inactivation of 90 percent of a population of a test organism under stated exposure conditions. Also referenced as the D10 Value or decimal reduction value. Exposure Time Time for which the sterilizer chamber is maintained within the specified range for temperature, sterilant concentration, pressure, and relative humidity. Also may be referred to as the time for which a medical device (load) is exposed at the specified sterilizing conditions. Failure Event in which a component does not perform one or more of its required functions within the specified limits under specified conditions. Flushing Procedure by which sterilant is removed from the load and chamber by either multiple alternate admissions of filtered air or inert gas and evacuations of the chamber or continuous passage of filtered air or inert gas through the load and chamber. Inactivation Loss of the ability of microorganisms to grow and/or multiply under specified culture conditions. Indicator Combination of the indicator agent and its substrate in the form in which it is intended to be used. Inoculated Carrier Carrier on which a defined number of test organisms have been deposited. Installation Qualification Obtaining and documenting evidence that equipment has been provided and installed in accordance with its specifications and that it functions within predetermined limits when operated in accordance with the operational instructions. Manufacturer Natural or legal person packaging or sterilizing a medical device. Medical Device Any instrument, apparatus, appliance, material, or other article, whether used alone or in Page 23

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

combination, including the software necessary for its proper application intended by the manufacturer to be used for human beings for the purpose of: diagnosis, prevention, monitoring, treatment, or alleviation of disease; diagnosis, monitoring, treatment, alleviation of, or compensation for an injury or handicap; investigation, replacement, or modification of the anatomy or of a physiological process; control of conception; and which does not achieve its principal intended action in or on the human body by pharmacological, immunological, or metabolic means, but which may be assisted in its function by such means. Microbial Barrier Ability of the packaging system to prevent the ingress of microorganisms under specified conditions. Microbiological Challenge Biological indicators, biological-indicator test packs, or inoculated product that contain known populations of microorganisms and can be used in testing sterilization cycles. Overkill Sterilization Process Process which is sufficient to provide at least a 12-logarithmic reduction or 12 D inactivation of an appropriately resistant biological indicator with an established D value. Package Integrity Unimpaired physical condition of a final package. Parametric Release Declaring product as sterile based on physical and/or chemical process data rather than on the basis of sample testing or biological indicator results. Performance Qualification Obtaining and documenting evidence that the equipment, as commissioned, will produce acceptable product when operated according to the processing specifications. Positive Sterility Test Sterility test samples which exhibit detectable microbial growth after incubation. Preconditioning Treatment of product prior to the sterilization cycle in a room or chamber to attain specified limits for temperature and relative humidity. Preconditioning Area Either a chamber or a room in which preconditioning occurs. Process Lethality Capability of the sterilization process to destroy microorganisms. Process Qualification Obtaining and documenting evidence that the sterilization process will produce acceptable health care products. Product Generic term used to describe raw materials, intermediate products, subassemblies, and finished medical devices. Product Qualification Obtaining and documenting evidence that the health care product will be acceptable for its intended use after exposure to the sterilization process. Qualification Documented evidence that all prescribed design and performance requirements are met. Page 24

TITLE:- VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: EFFECTIVE DATE:-

Requalification Repetition of part of all of the validation test requirements for the purpose of reconfirming process reliability. Sterilant Microbicidal agent in the physical form in which it is active. Sterile Free from viable microorganisms. In practice, no such absolute statement regarding the absence of microorganisms can be proven (see sterilization). Sterility State of being free from viable microorganisms. In practice, no such absolute statement regarding the absence of microorganisms can be proven (see sterilization). Sterility Assurance Level (SAL) Probability of a viable microorganism being present on a product unit after sterilization. SAL is normally expressed at 10-n. Sterility Test Test performed to determine if viable microorganisms are present. Sterilization Validated process used to render a product free from viable microorganisms. In a sterilization process, the nature of microbial death is described by an exponential function. Therefore, the presence of viable microorganisms on any individual item can be expressed in terms of probability. While this probability may be reduced to a very low number, it can never be reduced to zero. The probability can be expressed as a sterility assurance level (SAL). Sterilization Cycle Defined sequence of operational steps designed to achieve sterilization that is carried out in a sealed chamber. Specifically for EO sterilization, the treatment in a sealed chamber comprising air removal, conditioning, injection of sterilant, exposure to ethylene oxide, and removal of ethylene oxide. Sterilization Load Goods that are to be or have been sterilized simultaneously in the same sterilization chamber. Sterilization Process All treatments which are required to accomplish sterilization, including preconditioning, the sterilization cycle, and aeration. Validation A documented procedure for obtaining, recording, and interpreting the results needed to show that a process will consistently yield a product complying with predetermined specifications. Validation is considered as a total process that includes written protocol, evidence that the equipment as installed meets design criteria and specifications (equipment qualification), use of calibrated instruments to collect data, and evidence that the equipment can deliver the process within specified tolerances under established operating conditions and is reproducible as demonstrated by replicate runs and process challenges (performance qualification).

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