Document DDrg9MpvX8bj0JqxO2M7YXjeo

Lab /42 L 1538 TABLE OF CONTENTS SUMMARY INTRODUCTION MATERIALS METHODS DEVIATIONS RESULTS CONCLUSION RECORD STORAGE PHOTOGRAPH OF THE TEST ARTICLE APPENDIX SBRTC-2015-1052-2 4 5 5 6-7 .7 8 8 8 .9 10-12 Page 3 of 12 SHANGHAI BIOMATERIALS RESEARCH & TEST CENTER Add: 201, Building 2, NQ 427 Jumen Road, Shanghai, China Zip Code: 200023 TEL: 0086-21-63034903 FAX: OC Web site: www.sbrtc.com E-mail: 163.com Lab n L 1538 SBRTC-2015-1052-2 SUMMARY A guinea pig maximization test of the test article, Non--absorbable Surgical Suture (model: FIFE), was conducted to evaluate the skin sensitizing potential. This study was based on the International Organization for Standardization ISO 10993-10:2010: Biological evaluation of medical devices Part 10: Tests for irritation and skin sensitization; ISO 10993-12:2012: Biological evaluation of medical devices Part 12: Sample preparation and reference materials. 30 healthy young adult albino guinea pigs with body weight range from 300.1 g to 369.4 g were utilized. The test article was extracted in 0.9% sodium chloride injection (SC) and cotton seed oil (CSO) respectively. The test included intradermal induction phase, topical induction phase and challenge phase. In these phase, each extract was injected intradermally and patched occlusively to ten test guinea pigs (per extract) in an attempt to induce sensitization. The vehicle was similarly injected and patched occlusively to five reagent control guinea pigs (per vehicle). Following a recovery period, the test and reagent control animals were received a challenge patch of the appropriated test article extract and the reagent control. All sites were scored and the skin reactions for erythema and swelling were described and graded from 0-3 scale at 24h and 48h after patch removal. If the grades of less than 1 are seen in reagent control animals, grades of 1 or greater in the test group were generally indicated sensitization. Under the conditions of this study, at 24h and 48h after the challenge phase, the skin sites of the test and reagent control animals had no visible changes. It can be concluded that neither SC extracts nor CSO extracts of the test article had evidence of causing sensitization in the guinea pig. Study and Supervisory Personnel: FEI Yun MA Jiadong JIN Ruifen LU Hua Study Director: SUN Jiao, Ph.D. re-v of!' Date Completed SHANGHAI BIOMATERIALS RESEARCH & TEST CENTER Page 4 of 12 Add: 201, Building 2, No 427 Jumen Road, Shanghai, China Zip Code: 200023 TEL: 0086-21-63034903 FAX: 0 43 Web site: www.sbrtc.com E-mail: 163.com Lab Na L 1538 SBRTC-2015-1052-2 INTRODUCTION A guinea pig maximization study of the test article identified below was conducted to evaluate the potential to cause contact sensitization. This test was conducted based on the requirements of ISO 10993-10:2010: Biological evaluation of medical devices Part 10: Tests for irritation and skin sensitization. The test article was received on Jun. 16, 2015. Treatment began on Sep. 22, 2015, and the final observations were concluded on Oct. 20, 2015. This study, initiated by protocol signature on Aug. 11, 2015, was completed in the Lab of Shanghai Biomaterials Research & Test Center (SBRTC) and was conducted in accordance with the provisions of the ISO/TEC 17025-2005. MATERIALS The test article provided by the sponsor was identified and handled as follows: Test Article: Non-absorbable Surgical Suture (model: PTFE) <Specification: Z21302-60 (USP2-0/EP2.5)> Identification No: 150642 Sterilization Status: Sterilized Temperature Tolerance: -25--+55C (declaration from the sponsor) Extraction Vehicle: 0.9% sodium chloride injection (SC) <K15062018> Cotton seed oil (CSO) <MKBS9702V> Test Article Preparation: Based on the ISO ratio of 6cm2/ml [Surface area of the test sample to volume of extraction vehicle], 91.3cm2 of the test samples were covered 15.2 ml of extraction vehicle under sterile conditions for preparing the SC or CSO test extract at 37 'C for 72 hours respectively in each phase. The extracts were used within 1 hour after extraction. Reagent Control: The vehicles (without test article) were similarly prepared to serve as the reagent control. Condition of extracts: All the extracts of the test and control were clear. Additional materials: Freund's Complete Adjuvant (FCA) was mixed 50:50 (v/v) with the vehicle. A 10% (w/w) sodium dodecyl sulfate suspension in paraffin. In addition according ISO 10993-10 requirement, 5% mercaptobenzothiazole (dissolved in DMSO) as a positive control was used previously for another study last month. See the appendix I . Complete data is traceable in laboratory records. Page 5 of 12 SHANGHAI BIOMATERIALS RESEARCH & TEST CENTER Add: 201, Building 2, Ng. 427 Jumen Road, Shanghai, China Zip Code: 200023 TEL: 0086-21-63034903 FAX: 0" 3 Web site: www.sbrtc.com E-mail: 163,com Lab NQ L 1538 SBRTC-2015-1052-2 Test Animals: a) 0.1m1 of 50:50(v/v) mixture of FCA and the chosen vehicle b) 0.1ml of test extract c) 0.1ml of 50:50(v/v) mixture of a and b Reagent Control Animals: a) 0.1m1 of 50:50(v/v) mixture of FCA and the vehicle b) 0.1m1 of vehicle c) 0.1m1 of 50:50(v/v) mixture of a and b 2. Topical induction phase (Induction II): At 7th day after completion of the intradermal induction phase, the same area was clipped free of fur and treat with 10% sodium dodecyl sulfate suspension in paraffin. The suspension was massaged into the skin over the injection site to provoke a mild acute inflammation. The area was left uncovered. At 8th day, a 20mmx40mm section of absorbent gauze patch, saturated with freshly prepared the extract of the test article, and then was topically applied to the previously injected sites of the test animals. The reagent control animals were similarly patched with the appropriate reagent control. Each patch was secured with an occlusive dressing. The dressings and patches were removed after 48h. 3. Challenge phase At 22nd day, the fur was clipped and shaved from the left flank areas. At 23rd day, absorbent gauze patches were soaked with the corresponding solution at the concentration of site C, and patched on the left upper flank of each animal in test and reagent control group. Then the animals were secured with an occlusive dressing. The dressings and patches were removed after 24h. 4. Observation of animals The appearance of the challenge skin sites of the test and reagent control animals was observed respectively at 24h and 48h after removal of the dressing. The skin reactions for erythema and swelling were described and graded in according with the criteria shown below: Patch test reaction Grading scale No visible change 0 Discrete or patchy erythema 1 Moderate and confluent erythema 2 Intense erythema and swelling 3 If the grades of less than 1 are seen in reagent control animals, grades of 1 or greater in the test group were generally indicated sensitization. DEVIATIONS There were no deviations from the ISO 10993-10:2010 and SBRTC-PROTOCOL-2-261. Page 7 of 12 SHANGHAI BIOMATERIALS RESEARCH & TEST CENTER Add: 201, Building 2, N(2 427 Jumen Road, Shanghai, China Zip Code: 200023 TEL: 0086-21-63034903 FAX: 0 3 Web site: www.sbrtc.com E-mail: I163.com