Protocol #JIANAN-001 STERILIZATION VALIDATION PROTOCOL for Sterile Gauze Pad OVERVIEW: This document describes the method for development and validation of sterilization processes used for the sterile gauze Pad, which will be sterilized by Zhejiang Huanyi Medical Product Sterilization Co.,Ltd. It applies to microbiological, equipment, and process considerations related to the ability of the cycle and equipment to reliably and reproducibly sterilize the product when applied in accordance with process specifications. Other considerations are outside the scope of this document. The sterile gauze Pad is manufactured and designed for the purpose, which used for absorbing blood in body and extravasate, also cleaning wound, for use during various medical procedures & operations. Sterile gauze sponge is individually wrapped by paper bag. There are three sizes that are considered equivalent for sterilization. The size 4”x4”-8ply will be used for this validation. The validation strategy is an application of the Half-Cycle Overkill Method, performed in accordance with the current ISO 11135 -1994, and EN550. Successful completion of this study will demonstrate that the products can be reliably sterilized to a sterility assurance level (SAL) of 10-6. The validation practices defined by this document are the following: I. Documentation of proposed sterilization cycle. II. Documentation/Verification of Equipment Installation Qualification and Ongoing Calibration, Metrology, and Maintenance Programs. III. Operational Qualification. Ⅳ. Certification. PROCESS VALIDATION COMPONENTS Ⅰ. Documentation of Proposed Sterilization Cycle: The parameters and limits for the specified cycle are to be documented and approved by designated responsible representatives of ABC and Zhejiang Huanyi Medical Product Sterilization Co.,Ltd. The vehicle for this documentation shall be a supplement to the sterilization contract entitled PROCESS INSTRUCTION RECORD. The cycle parameters proposed for this cycle are as follows: Equipment: -Zhejiang Huanyi Medical Product Sterilization Co.,Ltd preconditioning Room #1. - Zhejiang Huanyi Medical Product Sterilization Co.,Ltd Sterilizers C, D, G, (Identical 667 ft Vacudyne ETO chambers, manufactured to the same specifications as defined under Vacudyne contracts number J93-27, 28, and 26, respectively). These process chambers utilize common utilities, steam source, and sterilant source, in addition to having been assembled and installed identically. They have been installation qualified as equivalent. -Zhejiang Huanyi Medical Product Sterilization Co.,Ltd preconditioning Room #1. Preconditioning: -Minimum initial product temperature prior to preconditioning: 70°F -Temperature: 90 -110°F -Relative Humidity: 45 -70% RH -Time: 18 – 96 Hrs. Sterilization: -Maximum Time to Load: 0.5 Hr. -Minimum Cycle Start Temp: 105°F -Process Temp. (during Exposure): 110 -125°F -Volatilizer Temp: 130 -190°F -Initial Evacuation: 10 INHGA -Nitrogen Dilutions (3): 10 -26 INHGA -Vacuum Break (Humidity Injection): 1.3 -1.7 INHG -Humidity Dwell: 75 – 150 Min. -Sterilant: 100% ETO -Sterilant Injection: 7.5 -9.1 INHG -Theoretical Concentration: 420 mg/L -Theoretical Weight: 17.8 lbs. -Nitrogen Blanket to: 27 INHGA -Exposure: 4 -8 Hrs. -Nitrogen Washes (3): 10 -27 INHGA -Air Washes (4): 10 -27 INHGA Aeration (QSR-97): -Minimum Residence Time: 24 Hrs. -Minimum Temperature: 75 °F -Minimum Air Exchange: 4197 Ft /M Ⅱ. Documentation/Verification of Equipment Installation Qualification and Ongoing Calibration, Metrology, and Maintenance Programs: This function is the responsibility of Zhejiang Huanyi Medical Product Sterilization Co.,Ltd. Zhejiang Huanyi Medical Product Sterilization Co.,Ltd warrants that all equipment has been installation qualified to assure that the process equipment can perform within its design specification (per definition of Installation Qualification in ANSI/AAMI/ISO 11135 -1994). Zhejiang Huanyi Medical Product Sterilization Co.,Ltd maintains documentation demonstrating such installation qualification and assures that the equipment continues to perform within its design specification through documented calibration and metrology practices consistent with the (GMP) requirements of 21CFR 820.70(g) and 21CFR 820.72, as well as formal maintenance practices including periodic empty chamber temperature distribution tests and leak tests. All practices are defined in sterilization maintenance and calibration sections of the Zhejiang Huanyi Medical Product Sterilization Co.,Ltd procedures. III. Operational/Qualification: Operational qualification of sterilization efficacy will be based upon a minimum of three successive Half-Cycle Overkill processes performed in accordance with ANSI/AAMI/ISO 11135 -1994, section 5, Performance Qualification. These half cycle processes will be parametrically identical to the proposed cycle specifications with the exception of the exposure time, which will be precisely one half of the minimum allowed process exposure time. In the performance of these qualification cycles, to the extent possible with process equipment of this size, cycle parameters will be held to "minimum" or "worst case" settings (i.e.: minimum preconditioning time, cycle start at 105°F, cycle temp set at 110°F, 0 gas makeups). An additional "fractional cycle" will be performed. This fractional cycle will be parametrically identical to the full and half cycles, the exception being an extremely abbreviated sterilant exposure time. The results of this fractional cycle will demonstrate the relative resistances of the product and spore strips, as placed, and will also serve to demonstrate the adequacy of the BI recovery (sterility) tests to be used in routine process monitoring. Procedure: All product samples provided for the testing services listed below will be destroyed. Samples will be disposed of at the laboratory. Bioburden Total aerobic bioburden of the product will be determined on 10 samples, randomly selected from the first lot, in accordance with Nantong Jianan Medical Products Co.,Ltd laboratory procedure number LAB-07. Additionally, bioburden recovery will be performed on 3 of these samples. The quantitative results from testing these samples will be included in the final report. Bacteriostasis Fungistasis Bacteriostasis Fungistasis testing will be performed by NAmSA on 6 samples. The quantitative results from testing these samples will be included in the final report. Spore Strip Enumeration Nantong Jianan Medical Products Co.,Ltd will perform verification of population of spore strips for lot(s) of biological indicators used in the validation (per LAB-17). Residual of Ethylene Oxide Adequate studies are to be performed to demonstrate that, at the time of earliest release, ETO residuals consistently fall below proposed FDA limits. In order to assure that these criteria are being met, three random samples will be removed, sterilized in separate cycles (Zhejiang Huanyi Medical Product Sterilization Co.,Ltd Cycle 26), and tested in accordance with procedures defined for determining Residual Ethylene Oxide, Residual Ethylene Chlorohydrin and Ethylene Glycol in Medical Devices. Each sample, tested on the day of earliest release, must demonstrate that the residual levels fall below those specified below. Nantong Jianan Medical Products Co.,Ltd has specified residual levels to be less than or equal to: 25 ppm EO, 25 ppm EC, and 250 ppm EG. Microbial Challenge Nantong Jianan Medical Products Co.,Ltd has selected the 4”x4”-8ply on the basis of sterilization process challenge. Nantong Jianan Medical Products Co.,Ltd will place two sets of spore strips provided, inside the product in the locations deemed to present the greatest potential sterilization challenge. Each Sterile Gauze Pad will be packaged in an inner pouch and also placed in an outer tray. The two sets of spore strips used in the validation are (1) strip of NAmSA’s SPORTROL code TN-6, and one (1) strip of STERIS’s SPORDEX NA005, which will be placed side by side within the product. Additionally, duplicate sets of the spore strips will be placed inside of poly/tyvek pouches and placed immediately adjacent to the product test units. The strips will contain a minimum assayed population of 1 x 10 spores of Bacillus atrophaeus. The Sterile Gauze Pad samples will be sent to Nantong Jianan Medical Products Co.,Ltd for product sterility testing. Sterility testing will be performed on the entire device-uncut. Nantong Jianan Medical Products Co.,Ltd will also test the biological indicators contained in these product samples and the biological indicators placed in pouches adjacent to the cable samples. All three half-cycles and the fractional cycle processes must contain no fewer than forty microbial challenge units. Each cycle will include 20 catheters and 20 pouches as described earlier. The units will be placed throughout the load in the areas identified to present the most difficult sterilization challenge. If no areas are known to present a more difficult challenge, samples may be distributed throughout the load geometrically or placed in convenient product locations that have been correlated with these sites in development studies or historically. A loading diagram will be prepared as a component of the process record indicating all sample locations. The half cycle loads will all contain the maximum corrugated cardboard density possible in a chamber load (630 lbs., minimum), along with suitable dunnage, product, and test samples. All components of the load will be documented. Physical Monitoring Twenty calibrated thermocouples (no fewer than nineteen must operate throughout the process) and one calibrated humidity sensor will be placed in each half-cycle process load prior to processing. The thermocouples are to be geometrically distributed, with each adjacent to a microbial challenge sample, through the test load with their locations documented. The humidity sensor must be located in the center of the product case, which is the most centrally located in the load. The product load is placed into the preconditioning room once the correct minimum temperature is achieved. The time into preconditioning, initial temperature, and initial RH are documented at this time. At the end of the ≤ 18-hour preconditioning, product temperature and relative humidity are reported, the humidity sensor is removed, and product is loaded into the sterilizer. The time required to load the sterilizer is to be documented. When the minimum cycle start temperature is achieved, the cycle is started. Process temperature, product temperatures, chamber pressure, sterilant weight used, and cycle event identification will automatically print throughout the duration of the process. Sterilant volatilizer temperature at the start of the cycle is to be documented in the process record. Temperature for one product load (lethal cycle) shall be monitored during the aeration period to satisfy the requirement specified in ANSI/AAMI/ISO 11135-1994, Section 5.3.4g. Acceptance Criteria: The physical process and microbiological components of the performance qualification are to be considered acceptable when: A) All whole product catheter samples from the three half cycle processes test sterile when cultured in accordance with ABC laboratory procedure LAB-08, or applicable contract lab procedure, consistent with the current monograph for sterility testing. B) All biological indicator microbial challenge samples from the three half cycle processes test sterile when cultured in accordance with ABC laboratory procedure LAB-06. C) The product is demonstrated to be non-bacteriostatic and non-fungistatic when tested in accordance with the current USP monograph for Bacteriostasis/Fungistasis (Laboratory procedure LAB-15) or applicable contract lab procedure. D) Positive cultures are obtained from fractional cycle biological indicators, and their number exceeds the number of whole product positive cultures from the process. E) An audit of records confirms that all recorded parameters for the half cycle processes conform to the cycle specifications proposed above. F) Product temperature range across the load during the exposure stage of the cycle is less than 18°F (10°C) at any given time. G) The correlation between the increase in pressure on steam addition and humidity has been documented. IV. Certification: All documents generated in the performance of the practices specified above must be maintained in a controlled permanent record. Upon completion of each phase of the validation, documents are to be reviewed and, if acceptable, approved by the designated quality assurance representative of the contractor. When complete, a validation report is to be compiled, by Nantong Jianan Medical Products Co.,Ltd, that is consistent with ANSI/AAMI/ISO 11135-1994; section 5.5. This report will summarize the results of the validation and contain (or refer to the location of) all documents generated in the performance of the validation practices. The documentation will include, but not be limited to, the following: A) Product Accountability/Tracking Records. B) Preconditioning Records. C) Sterilization Cycle Printout/Records. D) Loading Diagrams, Probe Placement Diagrams, and Sample Placement Diagrams. E) Aeration Records. F) Calibration Documents. G) Sterilant Certificates. H) Laboratory Reports. The validation report must demonstrate conformance with all physical and microbiological specifications. If acceptable, it will be signed as approved by the designated quality assurance representative of the contractor and forwarded the sponsor for review, approval, and filing. ROUTINE PROCESSING All process records for each routine load will receive a formal review to assure conformance with validated specifications prior to release. In addition, routine production loads will be biologically monitored. Twenty glassine enclosed spore strips, placed as in the validation studies (i.e.: in a pouch, adjacent to the product) will be distributed through the load geometrically. After processing, the strips will be removed and cultured in accordance with laboratory procedure LAB-06. All strips must test negative for the indicator organism as a condition of release. RE-VALIDATION In accordance with ANSI/AAMI/ISO 11135-1994, section 5.6, this "validation and any subsequent re-validation data shall be reviewed at least annually and the extent of re-validation determined and documented. Procedures for the review of validation and re-validation shall be documented and records of re-validation shall be retained. A re-validation report shall be documented. The report shall be signed by the same functionary that prepared, reviewed, and accepted the original validation report". INTERNAL DOCUMENTS LAB-06 -Sterility Testing of Inoculated Carriers (Spore Strips) used in Ethylene Oxide Sterilization LAB-08 -Procedure for Sterility Testing of Non-Liquid Devices LAB-15 -Bacteriostasis and Fungistasis –Direct Transfer LAB-17 -Identification and Enumeration of Inoculated Spore Strips LAB-20 -LAL Endotoxin Test Procedure QSR-92 -Sterilization Equipment Standard Operating Procedures -Preconditioning Process Parameters and Employee Instructions QSR-93 -Sterilization Equipment Standard Operating Procedures -Sterilization Parameters for 100% ETO QSR-96 -Sterilization Equipment Standard Operating Procedures -Sterilizer Loading QSR-97 -Sterilization Equipment Standard Operating Procedures -Sterilized Protocol Prepared By: Date: 2014-01-08 Nantong Jianan QA Manager Protocol Approved By: Date: Zhejiang Huanyi QA Manager 2014-01-08
