SUMMARY... 2 II. SCOPE... 3 III. LIST OF ABBREVIATIONS AND UNITS... 3 IV.

Transcription

1 TEST REPORT 14-0xx In Vitro Accelerated Fatigue Test: x Million Cycle Pulsatile Fatigue and Durability Test of Customer xmm Devices in a Overlapped Configuration Deployed in Curved Vessels Device Manufacturer: Customer Contact: Testing Facility Medical Device Testing Services, Inc Baker Rd Suite 430 Minnetonka, MN Test Engineer: Calvin Chao Job #: MDT140xx Date: I. SUMMARY... 2 II. SCOPE... 3 III. LIST OF ABBREVIATIONS AND UNITS... 3 IV. EQUIPMENT MACHINE CALIBRATION AND VALIDATIONS MAINTENANCE LAB CERTIFICATIONS... 5 V. PROCEDURES VESSEL INSPECTION VESSEL CONDITIONING DETERMINATION OF PHYSIOLOGICAL LOADING PARAMETERS... 7 a) Empty vessel compliance verification... 7 b) Physiological Loading Determination... 7 c) Physiological Loading Determination Validation ACCELERATED FATIGUE TEST SET UP INSPECTIONS PROCEDURE DEVIATIONS VI. RESULTS ACCELERATED FATIGUE TEST START: a) Test Monitoring INSPECTION DISASSEMBLY APPENDIX A: CALIBRATION RECORDS APPENDIX B: A2LA CERTIFICATE... ERROR! BOOKMARK NOT DEFINED. APPENDIX C: EQUATIONS APPENDIX D: ACCELERATED FATIGUE TEST DATA... 16

2 I. SUMMARY Customer device name devices (xmm) were tested to meet the requirements of FDA Recognized Consensus Standard (Recognition Number 3-87) ASTM F Standard Test Methods for in vitro Pulsatile Durability Testing of Vascular Devices FDA Guidance 1545 (2010) Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Devices and Associated Delivery Systems to evaluate durability when subjected to hydrodynamic loading that simulates the loading and/or change in diameter that the device will experience in vivo. Medical Device Testing Services (MDT) uses the Diameter Control Test Method (or Strain Control Method) described in Annex A2 of ASTM F This method uses a diameter measurement system (Laser) and vessels to ensure that the desired minimum and maximum device diameters, or the equivalent change in device diameter and mean device diameter, are achieved at the test frequency. x (x) devices were deployed in (x) vessels to their diameter xmm. To mimic the physiological application site, the devices were deployed in pairs in an overlapping configuration. The vessels were installed on the test instrument to maintain a xmm radius of curvature. The devices were subjected to x million strain controlled cycles on an EnduraTEC SGT in the Medical Device Testing Services lab (x/x/13 x/x/13). At the conclusion of the test, MDT performed a visual inspection (30x magnification) and no evidence of gross failure was observed. The devices within the testing vessels were returned to Customer for additional failure device analysis. Results only relate to the items tested, opinions and interpretations will be clearly marked as such in the test report. TR #: 14-0xx Page 2 of 23 3/27/2015 Job #:

3 II. SCOPE This benchtop test is used to determine the durability of a vascular device by exposing it to physiologically relevant diametric distension levels by means of hydrodynamic pulsatile loading. Device specimens are deployed in a vessel and subjected to the equivalent of x years post-implantation physiological stress, a minimum of x million cycles. The test method is applicable to balloon-expandable and self-expanding devices fabricated from metals and metal alloys. Test conditions are designed to meet the requirements of in vitro mechanical fatigue testing stated in ASTM F Standard Test Methods for in vitro Pulsatile Durability Testing of Vascular Devices and FDA Guidance 1545 (2010) Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Devices and Associated Delivery Systems. The test is controlled and monitored via the strain control method, which dictates that the test will control the diametric distention, relative to initial diameter of the vessel. III. LIST OF ABBREVIATIONS AND UNITS Abbreviation Description # Numbering, individual number %OD radial strain Outer diameter radial strain in percent % ID radial strain Inner diameter radial strain in percent avg% average bpm Beats per minute Comp Compliance dp delta Pressure ID Inner Diameter LVDT linear variable differential transformer n Number of samples NP Nominal Pressure OD Outer Diameter PBSS Phosphate Buffered (Isotonic) Saline Solution atm Atmosphere MDT Medical Device Testing Services SOP Standard Operating Procedure WI Work Instruction SGT stent/graft tester TR #: 14-0xx Page 3 of 23 3/27/2015 Job #:

4 IV. EQUIPMENT In accordance with ASTM F MDT uses the EnduraTEC SGT (Fig.1) which accommodates precision measurement and control of pressure, dimensions, and cycle counts. The general instrument features 4 to 12 vessels mounted between a pair of manifolds and linear motor driven pumps. The computer controlled system is capable of delivering radial strain to the devices under controlled temperature conditions. Laser micrometer measurement of radial strain is performed daily at repeated positions along each device to ensure that the desired strain levels are being met throughout the test duration. The following equipment was used: 1. Model 9100 EnduraTEC SGT (MDT SGT 91x0-0xx) 2. EnduraTEC WinTest Controls and Software 3. Keyence Laser Head and Controller (ISN00xxx) 4. Computer 400MHz CPU 5. Customer s Device size devices (CSP#xxx) 6. Inflation device (ISN00xxx) 3.5/20 balloon Lot # x 7. Silicone Vessel (n=1) x mm ID, 0. x mm wall thickness (physiological) 8. Silicone Vessels (n=x) x mm ID, 0. x mm wall thickness (thick walled) 9. Custom L fittings: n=24 r=xmm ± xmm 10. Magnifying glass with 10X magnification (ISN00925) 11. Olympus Videoscope with 30X magnification (ISN01068) 12. Nikon Microscope with 40X magnification (ISN01089) 13. Digital Camera (ISN00962) 14. Heater 0xx 15. RTD (ISNxxxxx) 16. Recirculator (ISNxxxxx) 17. ProAnalyst Software 18. Isotonic Saline Solution (PBSS): Lot # x a. Water b. Sodium Chloride 0.85% weight per volume c. Dihydrogen Potassium Phosphate - trace d. Sodium Dihydrogen Phosphate Monohydrate - trace e. Ethylene Glycol Monophenylether trace TR 14-xxx Page 4 of 23 3/27/2015

5 Fig. 1: EnduraTEC SGT MACHINE CALIBRATION AND VALIDATIONS Medical Device Testing Services calibrates, and maintains lab and facility equipment in accordance with A2LA ISO/IEC 17025:2005. ISO17025 is in compliance with GLP, GCP, and cgmp regulations for all activities performed by MDT these include; equipment generation, maintenance, calibration, measurement, and data collection The SGT 9100 EnduraTEC SGT (MDT SGT 91x0-00x), Keyence Laser Head and Controller, and the Heater used for this test were verified to be up to date with all calibration schedules. Calibration (Appendix A) was conducted according to MDT s SOP: Calibration and Preventative Maintenance (Doc# and ) and Calibration WI (Doc # 98105, 98106, 98107, 98116, and 98129). 2. MAINTENANCE No maintenance is scheduled to be performed during the test. If maintenance is performed, it will be listed in the results section and a justification will be provided. 3. LAB CERTIFICATIONS Tests are conducted in accordance with A2LA ISO/IEC 17025:2005, Testing Certificate Number: (Appendix B). TR 14-xxx Page 5 of 23 3/27/2015

6 V. PROCEDURES In accordance with MDT quality policy, the test protocol is the governing document for all tests performed. This test was conducted in accordance with test protocol ID# x reviewed and authorized by Customer. This protocol documented the diameter control test method described in ASTM F , Annex A2. This method reproduces the minimum and maximum diameters, or equivalent change in diameter at mean, that the device would see in vivo. To reproduce these diameters, a volume of testing fluid is injected into a fluid filled vessel that may or may not have a compliance that is physiologically relevant. Thick walled (thicker than physiological walls) vessels are used in order to achieve the desired higher frequency levels. The injected volume is adjusted so that the minimum diameter and maximum diameter of the device is equivalent to the minimum and maximum diameters that the device would experience under physiological conditions. The minimum and maximum loading diameters which simulate physiological loading conditions are determined using a physiological (thin walled) vessel. The general test sequence is as follows: Load vessel with physiological compliance behavior on the test instrument Run the system at 1.2Hz 160mmHg/80mmHg. Record max & min ID of the vessel. Deploy the device into the vessel and run the system at 1.2Hz 160mmHg/80mmHg. Record the max & min OD of the device = physiological loading Calculate the equivalent max & min OD of the device in a thicker walled vessel Install thick wall mock vessels on the test system. Deploy the devices. Start the fatigue test and adjust the volumetric displacement to achieve the physiological loading conditions. Monitor the test daily. Inspect devices according to protocol. TR 14-xxx Page 6 of 23 3/27/2015

7 1. VESSEL INSPECTION The silicone vessels were visually inspected for uniform color, general appearance, and uniform ID and wall thickness. No abnormalities were detected and the silicone vessels were accepted for test use. 2. VESSEL CONDITIONING In accordance with ASTM F , the empty vessels ID were verified on the test instrument after they had been mounted in their initial position. x (x) silicone vessels size x mm ID, 0.x mm wall thickness were mounted on the SGT 9100 EnduraTEC SGT. The tester was filled with Isotonic Saline Solution (PBSS) and then purged of air. The vessels were conditioned for 2 hours at expected test conditions: x Hz, displacement levels -/+ 0.x ml, 37 C. MDT used a laser micrometer to measure the non-deployed vessel OD along the length of the vessel under the dynamic test conditions. The data confirmed the conformity of the silicone vessels ID as well as the uniformity of the wall thickness between the x vessels. Additionally, each vessel was numbered and marked with left and right reference points 3. DETERMINATION OF PHYSIOLOGICAL LOADING PARAMETERS MDT and test protocol ID# x determine the minimum and maximum diameters (simulating physiological loading conditions) using a physiological (thin walled) vessel. Physiological loading conditions are identified by Customer, based on device application site. Test protocol ID# x identified a physiological compliance of x% -x%. a) Empty vessel compliance verification A straight thin walled silicone vessel (xmm ID, 0.xmm wall thickness) mounted on the tester (MDT SGT 91x0-00x) in the position of the pressure transducer. The vessel was mounted in a straight configuration. The tester was started and the controls were set to meet physiologic conditions identified in ASTM F ; 1.2 Hz (72 bpm) and 80 mmhg to 160 mmhg. The laser micrometer was used to measure the radial OD strain of the vessel every centimeter along the length of the vessel (Table 1). The empty vessel compliance was calculated using the experimental data (Table 1). The resulting x% for the xmm ID vessel met the test protocol requirements of x% - x%. (Appendix C: Equation 1, 2, 3) Physiological Compliance Empty Vessel: Dynamic %OD and %ID Radial Strain Compliance Positions(cm) OD-avg %OD Radial Strain over 1.2Hz: %OD Radial Strain Comp per Hz: %ID Radial Strain Comp per Hz: Mean of %ID Radial Strain Comp per Hz: Table 1: Physiological compliance data for the empty silicone vessel. b) Physiological Loading Determination The physiological vessel was then used to determine the physiological loading on the device, based on the device OD and the vessel OD relationship TR 14-xxx Page 7 of 23 3/27/2015

8 x (x) of Customer s devices were deployed into the straight physiological vessel according to test protocol ID# x. The devices were positioned at the center of the straight vessel with a target overlap of x- xmm (x- xmm acceptable). The tester was started and the controls were set to meet physiologic conditions identified in ASTM F2477-7; 1.2 Hz (72 bpm) and 80 mmhg to 160 mmhg (+/- 5mmHg). The laser micrometer was used to measure the radial OD strain of the vessel every centimeter along the length of the vessel (Fig 2, Table 2). The thick wall equivalent physiological loading condition (%OD strain) was then calculated. The result was 0.x % for devices deployed in xmm ID x 0.xmm wall vessels for the accelerated fatigue test (Appendix C: Equation 4, 5, 1) Fig. 2: Image showing the physiologic set-up and corresponding measurement locations. Positions (cm) OD-avg (mm) %OD Radial Strain %ID Radial Strain Mean %ID Radial Strain Physiological Loading Target %OD Radial Strain (thick wall equivalent) Table 2: Device OD and vessel OD relationship c) Physiological Loading Determination Validation The functionality, of the test method used with a device inside a vessel, depends on the device remaining in contact with the ID of the vessel throughout the distention cycle of that vessel. MDT compares OD vs pressure slope for an empty and deployed vessel to confirm that the test method is valid. The test method is valid if the OD slope of the deployed vessel is different than the OD slope of the non device deployed linear relationship with pressure. TR 14-xxx Page 8 of 23 3/27/2015

9 OD (mm) Confidential MDT measured the OD at a single position on both the empty and deployed vessel at 60, 80, 100, 120, 140, and 160mmHg. Results confirmed that the test method was valid (Fig. 3). 3.7 MDT120xx Customer 2.5mm Stent 420E6 Physiological Setup device deployed position 3.1x306deg device deployed position 6.2x44deg empty position 6.2x44deg Press (mmhg) Figure 3: OD of an empty silicone vessel vs the OD of the same vessel with a deployed device. 4. ACCELERATED FATIGUE TEST SET UP The devices were deployed in vessels designed to accommodate accelerated fatigue testing. These vessels have a thicker wall than the physiological vessels used in the determination of physiological loading. The device OD relationship with the vessel OD determined in previous steps was used to calculate the accelerated test conditions (0.x% OD strain for the xmm ID vessels) (Table 2). To provide a more realistic strain the vessels are installed on the test instrument in a bend to mimic physiological geometry. Customer s x mm devices were deployed according to test protocol ID# x into straight vessels on the benchtop. The deployment configuration consisted of x (x) devices deployed into each vessel (Table 3) with a x-x mm overlap located at the center of the vessel. Reference points were marked on the silicone tube indicating the left and right edges of the devices as well as the center. The straight vessel was installed on the SGT instrument in a curved configuration (xmm radius). The target curvature was verified using a digital camera and ProAnalyst measurement software (Appendix D). Station Vessel Size (mm) Left Device Lot- Instrum. # Right Device Lot- Instrum. # Overlap Length (mm) Total Length TR 14-xxx Page 9 of 23 3/27/2015

10 Table 3: Devices used for testing in test MDT12xxx. (mm) 5. INSPECTIONS 6. PROCEDURE DEVIATIONS Test Protocol ID #x required x VI. RESULTS 1. ACCELERATED FATIGUE TEST START: MDT uses the diameter control test method. To meet the ASTM F requirements the SGT test instrument volumetric displacement is controlled to maintain a targeted dimensional measurement (%OD strain). WinTest software maintains user defined volumetric displacement using a closed feedback loop and linear variable differential transformers (LVDTs), logs the cycle count, and monitors the system pressure. Daily measurements with a laser micrometer of the targeted %OD strain and OD mm (at repeatable points along the deployed vessel) are conducted to ensure that the test control parameters are correct. The SGT instrument was initiated at the protocol dictated test frequency (xhz) and the volumetric displacement levels adjusted until the target %OD strain (0.x%) was achieved (Table 2). MDT controls the test below target %OD at start up to avoid over testing the devices. Devices typically become conditioned in the first 500,000 cycles of testing and the %OD strain increases in response. a) Test Monitoring Testing conditions were observed and recorded daily to ensure proper instrument performance (Table 4). Pressure maximum and minimum values may reflect short term conditions during test instrument initiation and/or the presence of an air bubble. These values are recorded to track trends in instrument performance but do not affect the test conditions. The physiological loading is controlled via volumetric displacement. The volumetric displacement was adjusted as needed to maintain the correct %OD target strains (Table 5). TR 14-xxx Page 10 of 23 3/27/2015

11 Daily laser micrometer measurements were collected and recorded the cumulative results include: Results for deployment devices throughout the duration of the x0 x 10 6 cycle xhz accelerated fatigue test were mean %OD radial strain 0.x% (Appendix D Table 1). %ID radial strain was 0.x% (Appendix D Table 2). Mean OD (mm) was xmm (Appendix D Table 3). Mean ID (mm) was xmm (Appendix D Table 4). Temperature (C) Maximum Pressure (mmhg) Minimum Pressure (mmhg) P Table 4: Summary of testing conditions, recorded daily. Mean Minimum Maximum Start Finish Level 1 (ml) Level 2 (ml) End #Cycles (million) Frequency (Hz) Table 5: Alterations to the volumetric displacement levels to maintain the calculated target %OD radial strain on the devices throughout the accelerated fatigue test. 2. INSPECTION The devices were visually inspected, using a magnifying glass (10X, ISN#00925), at the completion of x million cycles. Inspection did not detect any visible signs of fracture, cracks or migration in the x Customer s xmm devices. A final device inspection was conducted at the conclusion of the test (x million cycles). The vessels were removed from the test instrument and the devices inspected with a 40x microscope. The devices were not removed from the vessels prior to inspection. Inspection did not detect any visible signs of fracture, cracks, or migration in the x Customer x mm devices. 3. DISASSEMBLY The devices were returned to Customer for further fracture analysis. The devices were not removed from their vessels prior to shipping. TR 14-xxx Page 11 of 23 3/27/2015

12 Revision Description of revision Date Medical Device Testing Services (MDT) tests are conducted in accordance with A2LA ISO/IEC 17025:2005, Testing Certificate Number: In compliance with this standard, MDT test reports include complete and accurate documentation of the test protocol and results. Information including the specific test conditions, statements of compliance or non-compliance with test protocol, statements of the estimated measurement uncertainty, and opinions or interpretations may be provided. Any test method deviations, additions or exclusions are documented and reviewed with the customer prior to beginning the test. Results only relate to the items tested, opinions and interpretations will be clearly marked as such in the test report. Additional information required by customer specific, or customer group specific, methods will also be noted. TR 14-xxx Page 12 of 23 3/27/2015

13 Appendix A: Calibration Records Equipment Calibration No. Component Identification Number Date Calibrated Calibration Due Date 1 Enduratec SGT 9100 System Displacement (LVDT) SGT91x0-00x 2 Pressure ISN 00xxx 3 Laser ISN 00xxx 4 Heater 0xx Temperature Box RTD Probe ISN 00xxx ISN 00xxx Table 1: Calibration schedule for the equipment used for MDT1xxxx TR 14-xxx Page 13 of 23 3/27/2015

14 Appendix B: A2LA Certificate TR 14-xxx Page 14 of 23 3/27/2015

15 Appendix C: Equations Equation 1: Strain Ratio [ ( ) ] a = OD radius of vessel b = ID radius of vessel υ = Poisson Ratio (.47) Equation 2: % ID Equation 3: % Compliance (ΔP = 100 mmhg) Equation 4: %ID Strain Equation 5: %OD Strain TR 14-xxx Page 15 of 23 3/27/2015

16 Appendix D: Accelerated Fatigue Test Data Average OD data for each vessel during the test. Vessels are loaded with 2 overlapped devices. For each vessel, five positions are measured along the deployed section (left end, center of left device, overlapped section, center of right device, right end). %OD Radial Strain Test Data Vessel# Laser Position %OD Mean %OD Minimum %OD Median %OD Maximum n= TR 14-xxx Page 16 of 23 3/27/2015

17 Vessel# Laser Position %OD Mean %OD Minimum %OD Median %OD Maximum n= Test Duration Mean Minimum Median Maximum n Overall Device Deployed Tube Radial Strain Table 1: Summary of %OD Radial Strain Test Data. %ID Radial Strain Test Data TR 14-xxx Page 17 of 23 3/27/2015

18 Vessel# Laser Position %ID Mean %ID Minimum %ID Median %ID Maximum n= TR 14-xxx Page 18 of 23 3/27/2015

19 Vessel# Laser Position %ID Mean %ID Minimum %ID Median %ID Maximum n= Test Duration Mean Minimum Median Maximum n Overall Device Deployed Tube Radial Strain Table 1: Summary of %ID Radial Strain Test Data. OD (mm) Test Data TR 14-xxx Page 19 of 23 3/27/2015

20 Vessel # Laser Position OD(mm) Mean OD(mm) Minimum OD(mm) Median OD(mm) Maximum n= TR 14-xxx Page 20 of 23 3/27/2015

21 Vessel # Laser Position OD(mm) Mean OD(mm) Minimum OD(mm) Median OD(mm) Maximum n= Test Duration Mean Minimum Median Maximum n Overall Device Deployed Tube OD (mm) Table 3: Summary of OD (mm) Test Data. TR 14-xxx Page 21 of 23 3/27/2015

22 ID (mm) Test Data Vessel # Laser Position ID(mm) Mean ID(mm) Minimum ID(mm) Median ID(mm) Maximum n= TR 14-xxx Page 22 of 23 3/27/2015

23 Vessel # Laser Position ID(mm) Mean ID(mm) Minimum ID(mm) Median ID(mm) Maximum n= Test Duration Mean Minimum Median Maximum n Overall Device Deployed Tube ID (mm) Table 4: Summary of ID (mm) Test Data. Note: ID (mm) calculated from the laser micrometer measured OD data (mm): ( ) Where: ID min = ID of vessel at 0mmHG OD mean = laser micrometer measurement OD min = ID min+2*wall thickness TR 14-xxx Page 23 of 23 3/27/2015