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MedDevice-Catalog Sterilization Validation

Sterilization Validation

All sterilization processes require validation of the efficacy and reproducibility of the process. Depending on the type of sterilization, this may be accomplished by partial, sub-lethal, or repetitive processing, using representative product and/or biological indicators. AppTec offers a full range of services in this area, from testing alone to full management of the validation.

Reusable Medical Device Validation

The FDA expects manufacturers to validate all reuse instructions including cleaning and disinfection procedures, cycle parameters, and aeration times, if applicable. AppTec offers a comprehensive program for evaluation of cleaning and sterilization processes for reusable medical devices.

Your AppTec Account Manager can provide you with initial information regarding
any of these testing programs. Also working closely with you will be a
highly trained and knowledgeable technical expert

           In this section
EO Half Cycle Sterilization Validation
Determination of Bioburden
    Bioburden Recovery Validation - Repetitive Recovery
    Bioburden Recovery Validation - Inoculation Method
Fractional Cycle Studies
    Inoculated Biological Indicators
    USP Product Sterility Test
    Bacteriostasis/Fungistasis
Terminal Sterilization Studies
    Biological Indicators
EO Residual Testing
    EO Residual Panel - Water Extraction
    EO Residual Panel - Headspace Extraction
ISO 11135 Performance Qualifications: Sensor and BI Requirements [Chart]
Radiation Sterilization Validation
Testing Requirements (per ISO and AAMI Standards) [Chart]
AppTec's Radiation Sterilization Validation Programs
AppTec's Dose Audit Programs
Reusable Medical Device Validation

EO Half Cycle Sterilization Validation Back to Top

For validation of ethylene oxide (EO) sterilization, certain steps must be followed as outlined in ISO and AAMI standards. As part of the performance qualification, a microbiological challenge must be performed to demonstrate the adequacy of the process to achieve the desired sterility assurance level (SAL). One of the most utilized methods is the half-cycle (overkill) method, which uses a biological indicator (BI) challenge, typically 10⁶ spores of Bacillus subtilis. Complete EO validation studies can be designed for a particular product and process, and all aspects of the studies follow the requirements of ISO and AAMI standards.

NOTE: Samples for EO Half Cycle Sterilization Validation testing should be shipped to AppTec’s St. Paul facility.

ESTIMATED TOTAL TESTING TIME: 4 - 6 weeks

1601000	Devices are selected at random for the bioburden recovery validation. They must be representative of the Worst Case Representative Family Designs being tested, but need not be identified with the production batches being used for validation. SAMPLE REQUIREMENTS 5-10 products For more information on these tests, see Page A-3.
Bioburden Recovery Efficiency - Repetitive Recovery Method OR 1602000 Bioburden Recovery Efficiency - Spore Inoculation Method

1603010	Non-sterile devices are tested for bioburden. SAMPLE REQUIREMENTS Minimum 10 products
Aerobic Bioburden Panel

1203000

Twenty (20) samples will contain the microbial challenge system (process challenge device) inoculated in the device's most difficult area to sterilize. The BI seeded samples can be simulated products if they are wholly representative of the actual finished product.

SAMPLE REQUIREMENTS 80 products (four sets of 20)

[See table on next page for sample size if chamber is larger than two (2) pallets.]

Inoculated Biological Indicators

USP Product Sterility Test	Twenty (20) product samples are removed from the load for sterility testing. (A minimum of 40 extra samples should be retained in the event a retest is required.) SAMPLE REQUIREMENTS 20 products
1220010 Extra Small [≤ 100 ml of media] 1220000 Small [101 to 200 ml of media] 1226000 Medium [201 to 400 ml of media] 1227000 Large [401 to 600 ml of media] 1228000 Extra Large [601 to 1200 ml of media]

190105	Sample device or material is tested for growth inhibition using the current USP organisms for Soybean-Casein Digest Medium (SCDM) and Fluid Thioglycollate Medium (FTM). (Additional organisms available upon request.) SAMPLE REQUIREMENTS 6 products
Bacteriostasis/Fungistasis

1201000	A minimum of five samples per pallet, but at least 10 samples per cycle will contain inoculated carriers (spore strips). These carriers will be tested for sterility according to client specifications and/or the USP. SAMPLE REQUIREMENTS Set of 10 [See table below for sample size if chamber is larger than two (2) pallets.]
Biological Indicators

195000

Samples from the terminal sterilization cycle will be tested for ethylene oxide residuals at incremental time periods. Suggested time periods are: immediately after sterilization, one day post-sterilization, three days post-sterilization, five days post-sterilization, and seven days post-sterilization. Additional time increments may be required and will be identified in the final report.

SAMPLE REQUIREMENTS Varies

EO Residual Panel -
Water Extraction

OR

194500

EO Residual Panel -
Headspace Extraction

ISO 1135 Performance Qualifications: Sensor and BI Sample Requirements
15 pallet	11 pallet	9 pallet	7 pallet	3 pallet	2 pallet	30 cu. ft.	25 cu. ft.
Load Dimensions
Width	48"	48"	48"	48"	42"	42"	21"	23"
Length	48"	48"	48"	48"	48"	48"	60"	51"
Height	78"	78"	78"	75"	72"	72"	30"	35"
Cubic Feet	1560	1144	936	700	252	168	22	24
performance qualifications
Commissioning/Physical
Preconditioning: TC/RH Sensor	40/19	29/14	25/12	19/9	9/4	7/3	5/2	5/2
Empty Chamber Temp Profile: TC Sensor	20	20	20	20	12	10	10	10
Conditioning: TC/RH Sensor	20/19	20/14	20/12	20/9	12/4	10/3	10/2	10/2
Microbiological
Biological Indicators (BI)	54	42	37	30	24	20	20	20
Routine Process
Biological Indicators (BI)	27	21	19	15	12	10	10	10
TC = Thermocouples RH = Relative Humidity

Radiation Sterilization Validation Back to Top

For validation of radiation (gamma, electron beam or x-ray) sterilization, certain steps must be followed as outlined in ISO and AAMI standards. As part of the performance qualification, a dose-setting or dose substantiation study must be performed to demonstrate the adequacy of the minimum dose to achieve the desired sterility assurance level (SAL). Several methods are available for validation of the minimum SAL dose, and the choice of method is dependent on a number of variables. Complete radiation validation studies can be designed for a particular product and process, and all aspects of the studies follow the requirements of ISO and AAMI standards.

AppTec offers three levels of service programs for sterilization validations,
as well as two levels of service programs for dose audits.
For descriptions of these programs, see below.

NOTE: Samples for radiation sterilization validation testing should be shipped to AppTec’s Atlanta facility.

test name	samples required	test description
AAMI/ISO 11137 Method 1 Validation
total turnaround time: 4-6 weeks m
Total Bioburden Panel	10 products from first batch	see section A (Bioburden/Microbial Assays)
Aerobic Bioburden Panel	10 products each from 2nd & 3rd batches	see section A (Bioburden/Microbial Assays)
Bioburden Recovery Efficiency Test	3-5 products from any batch	see section A (Bioburden/Microbial Assays)
Bacteriostasis / Fungistasis – One Medium	3 products from any batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	100 samples from one batch	see section G (Sterility Testing)
Dose Audit
Aerobic Bioburden Panel	10 products from one batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	100* samples from one batch	see section G (Sterility Testing)
m
AAMI/ISO 11137 Method 2 Validation
total turnaround time: 6-7 weeks m
The requirements of Method 2 are not outlined here due to the complexity of the sampling scheme. Please contact the laboratory for more information.
Dose Audit
Aerobic Bioburden Panel	10 products from one batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	100* samples from one batch	see section G (Sterility Testing)
*Reduced number of samples may apply. Contact laboratory.
m
m
test name	samples required	test description
AAMI TIR 27 (25 kGy) Validation
total turnaround time: 4-6 weeks m
Total Bioburden Panel	10 products from one batch	see section A (Bioburden/Microbial Assays)
Aerobic Bioburden Panel	10 products each from 2nd & 3rd batches	see section A (Bioburden/Microbial Assays)
Bioburden Recovery Efficiency Test	5-10 products from one batch	see section A (Bioburden/Microbial Assays)
Bacteriostasis / Fungistasis – One Medium	3 products from any batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	10 samples from one batch	see section G (Sterility Testing)
Quarterly Dose Audit
Aerobic Bioburden Panel	10 products from one batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	10 samples from one batch	see section G (Sterility Testing)
m
ISO/TR 13409 (25 kGy) Validation
total turnaround time: 4-6 weeks m
Total Bioburden Panel	10 products from one batch	see section A (Bioburden/Microbial Assays)
Bioburden Recovery Efficiency Test	5-10 products from one batch	see section A (Bioburden/Microbial Assays)
Bacteriostasis / Fungistasis – One Medium	3 products from any batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	10 samples from one batch	see section G (Sterility Testing)
Quarterly Dose Audit
Aerobic Bioburden Panel	10 products from one batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	10 samples from one batch	see section G (Sterility Testing)
m
AAMI/ISO 15844 Single-Batch Validation
total turnaround time: 4-6 weeks m
Total Bioburden Panel	10 products from batch	see section A (Bioburden/Microbial Assays)
Bioburden Recovery Efficiency Test	5-10 products from batch	see section A (Bioburden/Microbial Assays)
Bacteriostasis / Fungistasis – One Medium	3 products from batch	see section A (Bioburden/Microbial Assays)
Product Test of Sterility	100* samples from batch	see section G (Sterility Testing)

Radiation Sterilization Validation Programs Back to Top

To help clients get their products through the validation process, AppTec offer three levels of service options for validation studies and two levels of service options for dose audits – each with varying degrees of involvement.

Your choice of service levels would depend on how much of your company’s time, manpower and expertise you want to commit to your validation program. With the Level 1 option, we provide only the testing services. You schedule and manage all aspects of the irradiation services and you pull together all the documentation to present an organized study. With Level 2, in addition to the testing, we handle all the irradiation services. However, you are still responsible for producing the final documentation. With Level 3, we take care of everything. You simply choose the validation method, give us your product samples, and 4 to 6 weeks later we give you a completed validation and finished manual.

These programs are conducted by AppTec’s Atlanta facility.
Contact your Account Manager for more information.

V a l i d a t i o n P r o g r a m s

LEVEL 1

Testing Services
We perform the full panel of the specific tests required by the particular validation method you have chosen –– AAMI/ISO Method 1, Method 2,
the 25 kGy Method, or the Single-Batch Method.

[See above charts]

LEVEL 2

Testing Services + Irradiation Services
We perform all the required testing plus we provide the verification irradiation services –– we compute the dose calculations, coordinate all interaction with the sterilizer, ensure that samples are irradiated at the verification dose, and provide the confirmation of irradiation.

LEVEL 3

Total Management of the Validation Study
We perform all the required testing, provide verification irradiation services and produce a manual that includes the protocol, test reports and supporting documents as attachments to protocol, the official AAMI / ISO standards, irradiation documentation (instructions, dose certificates, etc.), and a final report summarizing the study.

Most programs that are validated for radiation sterilization require periodic dose audits.
AppTec offers two levels of service options for performing these audits.

D o s e A u d i t P r o g r a m s

LEVEL 1

Testing Services
We perform all the tests required for a particular dose audit.

LEVEL 2

Testing Services + Irradiation Services
We perform all the required testing plus we provide dose audit irradiation services and a dose audit summary. The summary contains the steps of the dose audit, provides a conclusion, and includes reports and supporting documents.

D o s e A u d i t R e m i n d e r P r o g r a m
The dose audit requirements for Method 1 and Method 2 validations now allow for reduction in the number of verification samples as well as a reduction in the frequency, based on certain criteria.
AppTec offers a dose audit reminder program that informs clients of their options and issues reminders when dose audits are due for each product or family of products.

T e s t C o d e s

validation method codes dose audit codes

LEVEL 1	LEVEL 2	LEVEL 3	LEVEL 1	LEVEL 2
AAMI/ISO 11137 Method 1	200100	200110	200120		200130	200140
AAMI/ISO 11137 Method 2	200300	200400	200600		200800	200900
AAMI TIR 27 (25 kGy) Method	200101	200102	200121		200131	200141
ISO13409 (25 kGy) Method	200150	200160	200170		200180	200190
AAMI/ISO 15844 Single-Batch Method	200200	200500	200700		N/A	N/A

NOTE: These test codes are for prepackaged/bundled programs. Clients may select services within any level.

Reusable Medical Device Validation Back to Top

When reusable medical devices are cleaned and sterilized in a health care facility, manufacturers are responsible for providing their customers with complete and comprehensive written instructions for handling, cleaning, disinfection and sterilization. The FDA expects manufacturers to validate all reuse instructions including cleaning and disinfection procedures, cycle parameters, and aeration times, if applicable.

AppTec offers a comprehensive program for evaluation of cleaning and sterilization processes for reusable medical devices. Testing follows the guidelines outlined in the AAMI Technical Information Report No. 12 ("Designing, Testing & Labeling Reusable Medical Devices for Reprocessing in Health Care Facilities: A Guide for Device Manufacturers"). This program assists the manufacturer in meeting the requirements of the FDA Reviewer Guidance: "Labeling Reusable Devices for Reprocessing in a Health Care Facility."

All samples for reusable medical device testing should be shipped to AppTec’s St. Paul facility.

Protocol Development
A custom protocol is written for each study, tailored specifically to the device and the manufacturer’s instructions for reuse. AppTec’s scientific staff assists clients in designing cleaning processes and developing protocols.
Cleaning Efficacy Studies
Manufacturers must verify the efficacy of their recommended cleaning processes. Following the manufacturer’s cleaning instructions, this study tests those processes using simulated soil inoculated with bacterial spores.
Sterilization Efficacy Studies
Manufacturers must provide health care facilities with detailed sterilization instructions for their particular medical device. Sterilization parameters are tested to determine capability of producing a sterility assurance level of at least 10^-6. Studies are available to evaluating the following sterilization processes: • Liquid chemical sterilants • Pre-vacuum, steam (121-123°C and 132-135°C) • Sterrad^TM (H₂O₂) • Gravity, steam (121-123°C and 132-135°C) • Ethylene Oxide (EO)
Support for Functionality Studies
These studies involve exposure to multiple cleaning and or sterilization cycles as part of the functionality studies required to determine the useful life of a device.

For more information on reusable device validation testing, contact your Account Manager.