Medtronic XOMED. Seal Integrity Inspection of Packaging for Sterile Product

Transcription

1 Medtronic XOMED Rev. BP Ref. 7.1 Page 1 of PURPOSE: 1.1 To provide a procedure for visual inspection of seal integrity and seal strength determination via burst test on sterile barrier packages. 2.0 SCOPE: 2.1 This procedure applies to the in-process inspection of seal integrity on sterile barrier packages. 2.2 This procedure applies to inspections conducted during sealer start-up (per applicable product XPI), such as (ARO) Burst Testing and Post-Peel Inspection. 2.3 This procedure applies to incoming inspection of supplier-made seals on pouches. 2.4 This procedure applies to post-sterilization inspections and/or functional testing for certain products. 3.0 ASSOCIATED DOCUMENTS: 3.1 Applicable Documents: SOP Top Level Procedure for Control of Non-Conforming Product SOP Division Procedure for Manufacturing Process Validation SOP Radiation Sterilization Validation, Processing and Dose Auditing SOP E-Beam Radiation Sterilization Validation, Processing and Dose Auditing QCFM QA Post Sterilization Inspection 3.2 Reference Documents: SOP Control of Reprocessing/Rework QCFM Sealer Operating Performance Log Alloyd Atlas Sealer QCFM Sealer Operating Performance Log Sencorp Sealer QCFM Sealer Operating Performance Log Urania Sealer A QCFM Sealer Operating Performance Log Hawo 06 Sealer QCFM Sealer Operating Performance Log APM 01 Sealer QCFM Sealer Operating Performance Log Belco 03 Sealer QCFM Sealer Operating Performance Log Accuseal 635 Sealer QCFM Sealer Operating Performance Log Sencorp Lab Sealer QCFM Sealer Operating Performance Log Urania Sealer B ASTM F1140 Standard Test Methods for Internal Pressurization Failure Resistance of Unrestrained Packages ASTM F2054 Standard Test Method for Burst Testing of Flexible Package Seals Using Internal Air Pressurization Within Restraining Plates ASTM F1886 Standard Test Method for Determining Integrity of Seals for Medical Packaging by Visual Inspection 4.0 GENERAL: 4.1 Responsibilities All Employees are responsible for identifying and reporting package and/or seal defects in the course of their manufacturing or inspection activities regardless of their responsibilities All Manufacturing personnel are responsible for adhering to this procedure during sealer start-up and in-process inspection and reporting any non-conformance to Team Leader(s), Quality Assurance, Quality Engineering and/or Packaging Engineering Receiving personnel are responsible for adhering to this procedure during incoming inspection of supplier made seals on pouches Quality Assurance (QA) Technicians are responsible for evaluating packaging and/or seal defects and following process outlined in SOP 037 if non-conformance is detected Quality Engineering is responsible for evaluating packaging and/or seal defects and following process outlined in SOP 037 if non-conformance is detected Packaging Engineering is responsible for evaluating packaging and/or seal defects and assisting Quality Engineering with determining appropriate corrective or preventive actions. Packaging Engineering is also responsible for reviewing and approving any changes to this procedure.

2 Rev. BP Ref. 7.1 Page 2 of Definitions (ARO) Burst Test: Method whereby packages are tested in an apparatus that internally pressurizes the package until the package fails, i.e. a seal ruptures. The test measure is the maximum pressure detected before the package fails, captured in units of in/h2o. Per this SOP, Burst Test is used to measure seal strength Open Package Method: Burst test method used to test flexible packages with one opened side Closed Package Method: Burst test method where the completely sealed package is internally pressurized through a puncture Post-Peel Inspection: Method whereby package seals are fully peeled apart and the adhesive residue is inspected for undesired seal characteristics. 4.3 Equipment: (ARO) Burst Tester: Pressure control and monitoring device used to conduct burst tests on porous and nonporous pouches and lidded trays Open Package Fixture: Fixture for conducting Open Package Method pressurized seal strength testing on porous and non-porous flexible pouches Closed Package Fixture: Stable Platform and fixture, generally used in conjunction with a Split Plate Restraining Fixture, for conducting Closed Package Method pressurized seal strength testing on fully sealed lidded trays Split Plate Restraining Fixture: Fixture, used in conjunction with Closed Package Fixture, designed to determine appropriate restraining fixture for applicable product/package.

3 Rev. BP Ref. 7.1 Page 3 of PROCEDURE: 5.1 Visual Inspection Visual Inspection is required for 100% in-process inspection of all pouch and tray seals Visual Inspection may be required for incoming inspection per applicable specifications Seals should be inspected at a distance of 12 to 18 inches from the eye. Magnification devices are not required All visual inspections should occur in a well-lit area (Illumination should be approximately 540 lumen/m 2 or 50 foot candles of white light or daylight on the specimen) Refer to visual aids provided in Figure 2 for pouch seals and Figure 3 for tray seals for acceptable and unacceptable seal characteristics observed during visual inspection In addition to visual inspection of the package seal, the remainder of the pouch, tray, and/or lid shall undergo visual inspection to insure package is free of dirt, stains, grease or oils, rust, particulate, burs, cracks, cuts, tears, broken pieces, burned or embedded materials, deformation, scratches or other damage that may affect performance or prevent use During sealer start-up, seals with questionable seal characteristics should not undergo (ARO) Burst Test and Post-Peel Inspection. If only one of the required start-up samples is questionable, the questionable package sample should be scrapped. A new pouch or tray and lid should be used to replace the scrapped sample for sealer start-up. If more than one of the required start-up samples is questionable, contact appropriate personnel for further investigation. NOTE: The initial burst test is not required to be completed before production starts. However, burst testing must be completed prior to finishing the first work order of the shift If questionable seal characteristics are found during normal sealing procedures after successful sealer startup procedures, the questionable package should be scrapped. A new pouch or tray and lid should be used to reseal the product If questionable seal characteristics persist during normal sealing procedures, contact appropriate personnel for further investigation Any additional seal characteristics or criteria for packaging noted in applicable product XPIs supersede the requirements outlined in this document A false positive could occur when the seam in the seal band of certain pouch sealers creates an indentation in the poly-side of a pouch (see Figure 1 below). This is acceptable provided the indentation is at an angle of 20 degrees and no other seal defects are noted on the specimen. Figure 1: Seal Indentation Caused by Seal Band Seam (Acceptable)

4 Rev. BP Ref. 7.1 Page 4 of 14 Figure 2: Visual Aids for Pouch Seals

5 Rev. BP Ref. 7.1 Page 5 of 14 Figure 3: Visual Aids for Tray Seals

6 Rev. BP Ref. 7.1 Page 6 of (ARO) Burst Test Burst testing may be required for incoming inspection of supplier made seals on pouches. The procedure for burst testing outlined in this SOP shall be followed During sealer start-up, burst testing may be required per applicable product XPI. Unless other burst test procedures are detailed in the product BOM or XPI, the procedure for burst testing outlined in this SOP shall be followed. (see Section 5.1) The applicable Sealer Operating Performance Log (see section 3.1) should be used to record sealer start-up Before using (ARO) Burst Tester, ensure proper set-up Check machine calibrations Press RESET until the SELECT MODE screen appears Move the cursor to BURST TEST Press SET and the BURST TEST set-up screen will appear Set the appropriate FLOW and SENSITIVITY testing parameters For Pouches, FLOW should be set to 5, SENSITIVITY should be set to For Trays, see table 2 for FLOW and SENSITIVITY settings Verify units are in. H2O Move the cursor to BURST TEST Press SET Setup appropriate test fixture and attach package Initiate Burst Test Press START The sterile barrier (i.e.: perimeter) seal must burst in order to determine correct burst strength. For Closed Package Fixture, if needle punctures thru tray lidding during test before a seal bursts, sample is acceptable provided minimum burst value was met Trays that have an island seal that burst during the initial test cycling (e.g. Repose tray packaging p/n 68C1366) will require a second test run to burst the sterile barrier (perimeter) seal. Note: If both island and perimeter seals burst during the same ARO test cycle, the burst value collected may be recorded on applicable inspection/manufacturing documentation Press START. First cycle runs and bursts island seal Press RESET and START. Second cycle runs and bursts perimeter seal ACCEPTANCE CRITERIA for (ARO) Burst Test: Packages subjected to (ARO) Burst Test must have a burst value greater than the minimum burst value specified in the tables below.

7 Rev. BP Ref. 7.1 Page 7 of 14 Table 1: Minimum Burst Values for Pouches Material Part Number Side A Side B Width of Pouch Length of Pouch Minimum BURST value in H 2 O 187 Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1073B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Metalized PET Metalized PET Metalized PET Metalized PET Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly

8 Rev. BP Ref. 7.1 Page 8 of 14 Part Number Side A Material Side B Width of Pouch Length of Pouch Minimum BURST value in H 2O 684 Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Metalized PET Metalized PET D1042 Paper Blue Tint Poly D3000 Paper Blue Tint Poly D3004 Paper Blue Tint Poly D3012 Paper Blue Tint Poly D3017 Paper Blue Tint Poly D3018 Paper Blue Tint Poly D3021 Paper Blue Tint Poly D3022 Paper Blue Tint Poly D3025 Paper Blue Tint Poly D3027 Paper Blue Tint Poly D3028 Paper Blue Tint Poly D3030 Tyvek 1073B 92 GA Poly D3036 Tyvek 1059B 48 GA Poly D3037 Tyvek 1059B 48 GA Poly D3038 Tyvek 1059B 48 GA Poly D3039 Tyvek 1059B 48 GA Poly D3040 Paper Blue Tint Poly D3044 Metalized PET Metalized PET D3045 Tyvek 1059B 48 GA Poly D3046 Paper Blue Tint Poly D3047 Paper Blue Tint Poly D3048 Tyvek 1059B 48 GA Poly D3049 Tyvek 1059B 48 GA Poly D3050 Tyvek 1059B 48 GA Poly D3051 Tyvek 1059B 48 GA Poly D3052 Paper Blue Tint Poly D3053 Paper Blue Tint Poly D3055 Metalized PET Metalized PET D3056 Metalized PET Metalized PET D3057 Metalized PET Metalized PET D3058 Metalized PET Metalized PET D3059 Metalized PET Metalized PET

9 Rev. BP Ref. 7.1 Page 9 of 14 Part Number Side A Material Side B Width of Pouch Length of Pouch Minimum BURST value in H 2 O 68D3063 Metalized PET Metalized PET D3064 Metalized PET Metalized PET D3065 Metalized PET Metalized PET D3066 Paper Blue Tint Poly D3067 Paper Blue Tint Poly D3070 Paper Blue Tint Poly D3071 Tyvek 1073B 92 GA Poly D3075 Metalized PET Metalized PET D3076 Metalized PET 48 GA Poly D3077 Metalized PET 48 GA Poly D3078 Paper Blue Tint Poly D3079 Paper Blue Tint Poly D3081 Paper Blue Tint Poly D3084 Metalized PET 48 GA Poly D3086 Paper Blue Tint Poly D3089 Tyvek 1073B 48 GA Poly D3090 Tyvek 1073B 48 GA Poly D3091 Tyvek 1073B 48 GA Poly D3092 Tyvek 1073B 48 GA Poly D3093 Tyvek 1073B 48 GA Poly D3094 Metalized PET 48 GA Poly D3095 Tyvek 1073B 48 GA Poly D3096 Tyvek 1073B 48 GA Poly D3097 Tyvek 1073B 48 GA Poly D3100 Tyvek 1073B 48 GA Poly D3101 Tyvek 1073B 48 GA Poly D3102 Tyvek 1073B 48 GA Poly D3103 Tyvek 1073B 92 GA Poly D3104 Tyvek 1073B Nylon D3105 Tyvek 1073B Nylon D3106 Metalized PET 48 GA Poly D3109 Metalized PET Metalized PET M726750B020 Tyvek 1073B Nylon M726750B939 Foil/Nylon Foil/Nylon M726750C338 Tyvek 1073B Nylon M726750C339 Tyvek 1073B Nylon M726750C340 Tyvek 1073B Nylon

10 Rev. BP Ref. 7.1 Page 10 of 14 Table 2: Minimum Burst Values for Trays P/N Tray / Blister Description Flow Sensitivity Test Fixture Burst Value (Min.) in H 2 O Tray Thermoformed, 5 X 10, Pillar 5 4 Pillar Tray Fixture 19 68C1032 Sinus Irrigation Tube Tray 5 1 Laser Shield Test Fixture Notch C1038 Laser Shield ET & EMG Tube Tray 5 1 Laser Shield Test Fixture Notch C1325 Blister Tray, PETG, Outer, NIM Pedicle 5 1 Laser Shield Fixture Notch C1326 Blister Tray, PETG, Inner, NIM Pedicle 5 1 Laser Shield Fixture Notch C1351 Blister Tray, PETG, Hydrodebrider, Hydrodebrider Tray Fixture 5 4 x x C C1352 Blister Tray, Slide on Sheath 5 4 VSI Sheath Tray Fixture 85 68C1355 Blister Tray, PETG, Tubing Sets 5 4 Tubing Sets Tray Fixture 17 68C1356 Tray, PETG, Hydrodebrider Inner 5 1 Hydrodebrider Inner Tray Fixture 10 68C1360 Blister Tray, PETG, Suction Irrigator 5 4 Suction Irrigator Fixture 13 68C1361 Tray, PETG, Hydrodebrider Outer 5 1 Hydrodebrider Outer Tray 9 68C1366 Blister Tray, PETG, Repose Inserter Inner C1367 Blister Tray, PETG, Repose Inserter Outer 5 1 Repose Inserter Inner Tray Fixture Repose Inserter Outer Tray Fixture 68C1369 Blister Tray, PETG, Repose Bone Screw 5 1 Repose Bone Screw Tray Fixture 43 68C1378 Tray, Chitosan Delivery System 5 1 Chitosan (NovaGen) Tray Fixture 17 * Ensure that the perimeter seal bursts per Section * 11

11 Rev. BP Ref. 7.1 Page 11 of Post-Peel Inspection Post-peel inspection may be required for incoming inspection of supplier made seals on pouches During sealer start-up, post-peel inspection may be required per applicable product XPI Post-peel inspection should not be used as an in-process inspection for any package The procedure for post-peel inspection consists of the following: Separate sealed materials from themselves by peeling from applicable corner of package Entire package should be peeled open Inspect peeled seal area for defects. Figure 4: Peel technique for Pouches Figure 5: Peel technique for Lidded Trays ACCEPTANCE CRITERIA for Post-Peel Inspection: Packages subjected to post-peel inspection must adhere to the following: Free of fiber tear, defined as loose, movable fibers on tray, lid, pouch, or product Free of encapsulation, defined as delamination wherein large sections of the Tyvek side of the pouch or lid remains in the seal area of the package which could impede sterile transfer of the product into the sterile field (see Figure 6). Figure 6: Accept and Reject Criteria for Encapsulation Seals shall conform to acceptable seal characteristics noted in the visual aids provided in Figure 2 for pouch seals and Figure 3 for tray seals in section 5.1 above False voids may occur when peeling certain tray seals. For peeled tray seals with apparent voids, a visual inspection of the matching adhesive on the lid stock is required. A glossy appearance on the lid matching the void pattern on the tray indicates the seal was complete prior to peeling. If the patterns do not match or if the void location appears on the same spot on multiple sealer start-up samples, contact appropriate personnel for further investigation.

12 Rev. BP Ref. 7.1 Page 12 of Functional Post Sterilization Inspection: Post Sterile sampling plan: Sampling for functional post sterilization testing and inspection is intended for process auditing and not for acceptance sampling. Samples are prepared by manufacturing personnel prior to sterilization as part of normal production as per XPI instructions. QA Technicians audit these products after sterilization by conducting 100% visual and destructive inspection of the samples provided Packaging Testing; Manufacturing operators perform sampling inspection of pouches sealed on identified sealing equipment during the work order process for product packaging and sealers used in each sterile load. Samples are obtained by the manufacturing operators during the manufacturing packaging process per the XPI or XII, the samples are then placed into cartons marked QA Package Test Samples, and included with each sterile load prior to sterilization process Each QA Package Test Samples are comprised of a minimum of 5 (five) sample pouches, sealed lid packages, or other sealed package obtained from a Single work order during the course of manufacturing and packaging per the XPI or XII. Carton and label samples with the Work Order #, Sealing Equipment #, product # and pouch # or pouch/package size, date and time selected for test sampling on QCFM Sampling plan for test package and subsequent product functional sample testing is derived from ANSI/ASQZ 1.4 as justified by the pre-sterilization testing on seal integrity. This QA final sampling of (five minimum) selected test samples from the identified sealer equipment is an audit to observe any changes in MI and II attributes after sterilization and confirms product suitability for QA final release Prior to load final release, QA is delivered the QA Package Test Samples and QCFM 067. QA shall verify Load Number, Purchase Order, Packing List, Sterilization Certification per SOP 389 for Gamma or SOP 582 for E-Beam Testing and Inspection: Test results are documented on QCFM 067 to record the selected test sample, identify the Work Order/Lot #, Sealer Equipment I.D. #, product #, description/family #, and pouch #/tray # or pouch/package size. QCFM 067 shall be retained with the load release packet Packaging Visual Testing: For each sterile load containing any identified Product Family types in Table 3, QA selects a minimum of 5 (five) random finished units (products within pouches / seals packages), of a minimum of 1 identified product from each of the Product Family types. QA individually inspects the package seals for any physical / functional defects, i.e., tears, ruptured seals, holes, voids, or channels, contamination, etc After sterilization, packaging seals are no longer considered in-process. Certain seal defects (as shown in Figure 1 for pouches and Figure 2 for trays) may be acceptable provided a minimum of 1/8 of uninterrupted seal remains; however, this is at the discretion of Quality Engineering and Packaging Engineering following investigation Packaging Functional Testing: For each sterile load containing any identified Product Family types in Table 3, QA selects a minimum of 5 (five) random finished units (products within pouches / seals packages), of a minimum of 1 identified product from each of the Product Family types QA conducts destructive testing (ARO Burst Test per section 5.1.1, and Peel Test per section 5.2.1) of each identified Product Family types samples in accordance to the MI, II, or XPI for the product Product Visual and Functional Testing: Finished product units of use for functional testing can be obtained from the packaging samples. QA conducts destructive testing of samples per Table 3 below and in accordance to the MI, II, or XPI for the product Functional Test for Vari-stim III Post Sterile EO Ensure that LED lights on each of the three settings when contact is made between needle and probe Functional Test for Pulsatron II Post Sterile EO Ensure that LED lights when contact is made between needle and probe when button is depressed.

13 Rev. BP Ref. 7.1 Page 13 of 14 Table 3: Post-Sterilization Functional Product Family Test Table Family Number Product Family Typical Product # Description Product Testing Required 1 Pulsatron Yes 2 Vari-Stim III Yes

14 Rev. BP Ref. 7.1 Page 14 of 14 Attachment A: Minimum Burst Value Calculation 1. Minimum Burst Values for pouches are derived from the formula: Burst Pressure = (Perimeter) x 454 OR 2 (L + W) x 454 OR (Inner Seal Perimeter) x 454 (Area) x (L x W) x (Area of Inner Seal) x Where: L = inner length of seal W = inner width of seal For pouches with a Side A material of Tyvek 1059, multiply final value derived from formula above by 0.75 to obtain minimum burst value. For pouches with a Side B material of Nylon, multiply final value derived from formula above by 0.75 to obtain minimum burst value. This formula also applies to tray seals. Perimeter and Area were measured using the following diagrams: CHEVRON POUCH CORNER CUT POUCH Perimeter = 2P + 2R + J Perimeter = 2P + S + T + R + J Area = (P x J) + [O x (J/2)] Area = (P x J) + (S x T) + [S x (U/2)] 2. Burst test formula derived from Thomas P. Wachala article Correlating Tensile & Burst Tests in Pouches from 1991 edition of Medical Device & Diagnostic Industry. 3. Minimum burst value correlates to minimum tensile value for seal strength. Industry practice prescribes a minimum tensile value of 0.75 to 1.0 (lbf) pounds of force based on material. 4. The burst values calculated are provided as a minimum requirement. Process validation for heat sealers is required per SOP 327.

15 Medtronic XOMED Rev. BO BP Ref. 7.1 Page 1 of PURPOSE: 1.1 To provide a procedure for visual inspection of seal integrity and seal strength determination via burst test on sterile barrier packages. 2.0 SCOPE: 2.1 This procedure applies to the in-process inspection of seal integrity on sterile barrier packages. 2.2 This procedure applies to inspections conducted during sealer start-up (per applicable product XPI), such as (ARO) Burst Testing and Post-Peel Inspection. 2.3 This procedure applies to incoming inspection of supplier-made seals on pouches. 2.4 This procedure applies to post-sterilization inspections and/or functional testing for certain products. 3.0 ASSOCIATED DOCUMENTS: 3.1 Applicable Documents: SOP Top Level Procedure for Control of Non-Conforming Product SOP Division Procedure for Manufacturing Process Validation SOP Radiation Sterilization Validation, Processing and Dose Auditing SOP E-Beam Radiation Sterilization Validation, Processing and Dose Auditing QCFM QA Post Sterilization Inspection 3.2 Reference Documents: SOP Control of Reprocessing/Rework QCFM Sealer Operating Performance Log Alloyd Atlas Sealer QCFM Sealer Operating Performance Log Sencorp Sealer QCFM Sealer Operating Performance Log Urania Sealer A QCFM Sealer Operating Performance Log Hawo 06 Sealer QCFM Sealer Operating Performance Log APM 01 Sealer QCFM Sealer Operating Performance Log Belco 03 Sealer QCFM Sealer Operating Performance Log Accuseal 635 Sealer QCFM Sealer Operating Performance Log Sencorp Lab Sealer QCFM Sealer Operating Performance Log Urania Sealer B ASTM F1140 Standard Test Methods for Internal Pressurization Failure Resistance of Unrestrained Packages ASTM F2054 Standard Test Method for Burst Testing of Flexible Package Seals Using Internal Air Pressurization Within Restraining Plates ASTM F1886 Standard Test Method for Determining Integrity of Seals for Medical Packaging by Visual Inspection 4.0 GENERAL: 4.1 Responsibilities All Employees are responsible for identifying and reporting package and/or seal defects in the course of their manufacturing or inspection activities regardless of their responsibilities All Manufacturing personnel are responsible for adhering to this procedure during sealer start-up and in-process inspection and reporting any non-conformance to Team Leader(s), Quality Assurance, Quality Engineering and/or Packaging Engineering Receiving personnel are responsible for adhering to this procedure during incoming inspection of supplier made seals on pouches Quality Assurance (QA) Technicians are responsible for evaluating packaging and/or seal defects and following process outlined in SOP 037 if non-conformance is detected Quality Engineering is responsible for evaluating packaging and/or seal defects and following process outlined in SOP 037 if non-conformance is detected Packaging Engineering is responsible for evaluating packaging and/or seal defects and assisting Quality Engineering with determining appropriate corrective or preventive actions. Packaging Engineering is also responsible for reviewing and approving any changes to this procedure.

16 Rev. BO BP Ref. 7.1 Page 2 of Definitions (ARO) Burst Test: Method whereby packages are tested in an apparatus that internally pressurizes the package until the package fails, i.e. a seal ruptures. The test measure is the maximum pressure detected before the package fails, captured in units of in/h2o. Per this SOP, Burst Test is used to measure seal strength Open Package Method: Burst test method used to test flexible packages with one opened side Closed Package Method: Burst test method where the completely sealed package is internally pressurized through a puncture Post-Peel Inspection: Method whereby package seals are fully peeled apart and the adhesive residue is inspected for undesired seal characteristics. 4.3 Equipment: (ARO) Burst Tester: Pressure control and monitoring device used to conduct burst tests on porous and nonporous pouches and lidded trays Open Package Fixture: Fixture for conducting Open Package Method pressurized seal strength testing on porous and non-porous flexible pouches Closed Package Fixture: Stable Platform and fixture, generally used in conjunction with a Split Plate Restraining Fixture, for conducting Closed Package Method pressurized seal strength testing on fully sealed lidded trays Split Plate Restraining Fixture: Fixture, used in conjunction with Closed Package Fixture, designed to determine appropriate restraining fixture for applicable product/package.

17 Rev. BO BP Ref. 7.1 Page 3 of PROCEDURE: 5.1 Visual Inspection Visual Inspection is required for 100% in-process inspection of all pouch and tray seals Visual Inspection may be required for incoming inspection per applicable specifications Seals should be inspected at a distance of 12 to 18 inches from the eye. Magnification devices are not required All visual inspections should occur in a well-lit area (Illumination should be approximately 540 lumen/m 2 or 50 foot candles of white light or daylight on the specimen) Refer to visual aids provided in Figure 2 for pouch seals and Figure 3 for tray seals for acceptable and unacceptable seal characteristics observed during visual inspection In addition to visual inspection of the package seal, the remainder of the pouch, tray, and/or lid shall undergo visual inspection to insure package is free of dirt, stains, grease or oils, rust, particulate, burs, cracks, cuts, tears, broken pieces, burned or embedded materials, deformation, scratches or other damage that may affect performance or prevent use During sealer start-up, seals with questionable seal characteristics should not undergo (ARO) Burst Test and Post-Peel Inspection. If only one of the required start-up samples is questionable, the questionable package sample should be scrapped. A new pouch or tray and lid should be used to replace the scrapped sample for sealer start-up. If more than one of the required start-up samples is questionable, contact appropriate personnel for further investigation. NOTE: The initial burst test is not required to be completed before production starts. However, burst testing must be completed prior to finishing the first work order of the shift If questionable seal characteristics are found during normal sealing procedures after successful sealer startup procedures, the questionable package should be scrapped. A new pouch or tray and lid should be used to reseal the product If questionable seal characteristics persist during normal sealing procedures, contact appropriate personnel for further investigation Any additional seal characteristics or criteria for packaging noted in applicable product XPIs supersede the requirements outlined in this document A false positive could occur when the seam in the seal band of certain pouch sealers creates an indentation in the poly-side of a pouch (see Figure 1 below). This is acceptable provided the indentation is at an angle of 20 degrees and no other seal defects are noted on the specimen. Figure 1: Seal Indentation Caused by Seal Band Seam (Acceptable)

18 Rev. BO BP Ref. 7.1 Page 4 of 14 Figure 2: Visual Aids for Pouch Seals

19 Rev. BO BP Ref. 7.1 Page 5 of 14 Figure 3: Visual Aids for Tray Seals

20 Rev. BO BP Ref. 7.1 Page 6 of (ARO) Burst Test Burst testing may be required for incoming inspection of supplier made seals on pouches. The procedure for burst testing outlined in this SOP shall be followed During sealer start-up, burst testing may be required per applicable product XPI. Unless other burst test procedures are detailed in the product BOM or XPI, the procedure for burst testing outlined in this SOP shall be followed. (see Section 5.1) The applicable Sealer Operating Performance Log (see section 3.1) should be used to record sealer start-up Before using (ARO) Burst Tester, ensure proper set-up Check machine calibrations Press RESET until the SELECT MODE screen appears Move the cursor to BURST TEST Press SET and the BURST TEST set-up screen will appear Set the appropriate FLOW and SENSITIVITY testing parameters For Pouches, FLOW should be set to 5, SENSITIVITY should be set to For Trays, see table 2 for FLOW and SENSITIVITY settings Verify units are in. H2O Move the cursor to BURST TEST Press SET Setup appropriate test fixture and attach package Initiate Burst Test Press START The sterile barrier (i.e.: perimeter) seal must burst in order to determine correct burst strength. For Closed Package Fixture, if needle punctures thru tray lidding during test before a seal bursts, sample is acceptable provided minimum burst value was met Trays that have an island seal that burst during the initial test cycling (e.g. Repose tray packaging p/n 68C1366) will require a second test run to burst the sterile barrier (perimeter) seal. Note: If both island and perimeter seals burst during the same ARO test cycle, the burst value collected may be recorded on applicable inspection/manufacturing documentation Press START. First cycle runs and bursts island seal Press RESET and START. Second cycle runs and bursts perimeter seal ACCEPTANCE CRITERIA for (ARO) Burst Test: Packages subjected to (ARO) Burst Test must have a burst value greater than the minimum burst value specified in the tables below.

21 Rev. BO BP Ref. 7.1 Page 7 of 14 Table 1: Minimum Burst Values for Pouches Material Part Number Side A Side B Width of Pouch Length of Pouch Minimum BURST value in H 2 O 187 Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1073B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Metalized PET Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Metalized PET Metalized PET Metalized PET Metalized PET Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly

22 Rev. BO BP Ref. 7.1 Page 8 of 14 Part Number Side A Material Side B Width of Pouch Length of Pouch Minimum BURST value in H 2O 684 Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Tyvek 1059B 48 GA Poly Metalized PET Metalized PET D1042 Paper Blue Tint Poly D3000 Paper Blue Tint Poly D3004 Paper Blue Tint Poly D3012 Paper Blue Tint Poly D3017 Paper Blue Tint Poly D3018 Paper Blue Tint Poly D3021 Paper Blue Tint Poly D3022 Paper Blue Tint Poly D3025 Paper Blue Tint Poly D3027 Paper Blue Tint Poly D3028 Paper Blue Tint Poly D3030 Tyvek 1073B 92 GA Poly D3036 Tyvek 1059B 48 GA Poly D3037 Tyvek 1059B 48 GA Poly D3038 Tyvek 1059B 48 GA Poly D3039 Tyvek 1059B 48 GA Poly D3040 Paper Blue Tint Poly D3044 Metalized PET Metalized PET D3045 Tyvek 1059B 48 GA Poly D3046 Paper Blue Tint Poly D3047 Paper Blue Tint Poly D3048 Tyvek 1059B 48 GA Poly D3049 Tyvek 1059B 48 GA Poly D3050 Tyvek 1059B 48 GA Poly D3051 Tyvek 1059B 48 GA Poly D3052 Paper Blue Tint Poly D3053 Paper Blue Tint Poly D3055 Metalized PET Metalized PET D3056 Metalized PET Metalized PET D3057 Metalized PET Metalized PET D3058 Metalized PET Metalized PET D3059 Metalized PET Metalized PET

23 Rev. BO BP Ref. 7.1 Page 9 of 14 Part Number Side A Material Side B Width of Pouch Length of Pouch Minimum BURST value in H 2 O 68D3063 Metalized PET Metalized PET D3064 Metalized PET Metalized PET D3065 Metalized PET Metalized PET D3066 Paper Blue Tint Poly D3067 Paper Blue Tint Poly D3070 Paper Blue Tint Poly D3071 Tyvek 1073B 92 GA Poly D3075 Metalized PET Metalized PET D3076 Metalized PET 48 GA Poly D3077 Metalized PET 48 GA Poly D3078 Paper Blue Tint Poly D3079 Paper Blue Tint Poly D3081 Paper Blue Tint Poly D3084 Metalized PET 48 GA Poly D3086 Paper Blue Tint Poly D3089 Tyvek 1073B 48 GA Poly D3090 Tyvek 1073B 48 GA Poly D3091 Tyvek 1073B 48 GA Poly D3092 Tyvek 1073B 48 GA Poly D3093 Tyvek 1073B 48 GA Poly D3094 Metalized PET 48 GA Poly D3095 Tyvek 1073B 48 GA Poly D3096 Tyvek 1073B 48 GA Poly D3097 Tyvek 1073B 48 GA Poly D3100 Tyvek 1073B 48 GA Poly D3101 Tyvek 1073B 48 GA Poly D3102 Tyvek 1073B 48 GA Poly D3103 Tyvek 1073B 92 GA Poly D3104 Tyvek 1073B Nylon D3105 Tyvek 1073B Nylon D3106 Metalized PET 48 GA Poly D3109 Metalized PET Metalized PET M726750B020 Tyvek 1073B Nylon M726750B939 Foil/Nylon Foil/Nylon M726750C338 Tyvek 1073B Nylon M726750C339 Tyvek 1073B Nylon M726750C340 Tyvek 1073B Nylon

24 Rev. BO BP Ref. 7.1 Page 10 of 14 Table 2: Minimum Burst Values for Trays P/N Tray / Blister Description Flow Sensitivity Test Fixture Burst Value (Min.) in H 2 O Tray Thermoformed, 5 X 10, Pillar 5 4 Pillar Tray Fixture 19 68C1032 Sinus Irrigation Tube Tray 5 1 Laser Shield Test Fixture Notch C1038 Laser Shield ET & EMG Tube Tray 5 1 Laser Shield Test Fixture Notch C1325 Blister Tray, PETG, Outer, NIM Pedicle 5 1 Laser Shield Fixture Notch C1326 Blister Tray, PETG, Inner, NIM Pedicle 5 1 Laser Shield Fixture Notch C1351 Blister Tray, PETG, Hydrodebrider, Hydrodebrider Tray Fixture 5 4 x x C C1352 Blister Tray, Slide on Sheath 5 4 VSI Sheath Tray Fixture 85 68C1355 Blister Tray, PETG, Tubing Sets 5 4 Tubing Sets Tray Fixture 17 68C1356 Tray, PETG, Hydrodebrider Inner 5 1 Hydrodebrider Inner Tray Fixture 10 68C1360 Blister Tray, PETG, Suction Irrigator 5 4 Suction Irrigator Fixture 13 68C1361 Tray, PETG, Hydrodebrider Outer 5 1 Hydrodebrider Outer Tray 9 68C1366 Blister Tray, PETG, Repose Inserter Inner C1367 Blister Tray, PETG, Repose Inserter Outer 5 1 Repose Inserter Inner Tray Fixture Repose Inserter Outer Tray Fixture 68C1369 Blister Tray, PETG, Repose Bone Screw 5 1 Repose Bone Screw Tray Fixture 43 68C1378 Tray, Chitosan Delivery System 5 1 Chitosan (NovaGen) Tray Fixture 17 * Ensure that the perimeter seal bursts per Section * 11

25 Rev. BO BP Ref. 7.1 Page 11 of Post-Peel Inspection Post-peel inspection may be required for incoming inspection of supplier made seals on pouches During sealer start-up, post-peel inspection may be required per applicable product XPI Post-peel inspection should not be used as an in-process inspection for any package The procedure for post-peel inspection consists of the following: Separate sealed materials from themselves by peeling from applicable corner of package Entire package should be peeled open Inspect peeled seal area for defects. Figure 4: Peel technique for Pouches Figure 5: Peel technique for Lidded Trays ACCEPTANCE CRITERIA for Post-Peel Inspection: Packages subjected to post-peel inspection must adhere to the following: Free of fiber tear, defined as loose, movable fibers on tray, lid, pouch, or product Free of encapsulation, defined as delamination wherein large sections of the Tyvek side of the pouch or lid remains in the seal area of the package which could impede sterile transfer of the product into the sterile field (see Figure 6). Figure 6: Accept and Reject Criteria for Encapsulation Seals shall conform to acceptable seal characteristics noted in the visual aids provided in Figure 2 for pouch seals and Figure 3 for tray seals in section 5.1 above False voids may occur when peeling certain tray seals. For peeled tray seals with apparent voids, a visual inspection of the matching adhesive on the lid stock is required. A glossy appearance on the lid matching the void pattern on the tray indicates the seal was complete prior to peeling. If the patterns do not match or if the void location appears on the same spot on multiple sealer start-up samples, contact appropriate personnel for further investigation.

26 Rev. BO BP Ref. 7.1 Page 12 of Functional Post Sterilization Inspection: Post Sterile sampling plan: Sampling for functional post sterilization testing and inspection is intended for process auditing and not for acceptance sampling. Samples are prepared by manufacturing personnel prior to sterilization as part of normal production as per XPI instructions. QA Technicians audit these products after sterilization by conducting 100% visual and destructive inspection of the samples provided Packaging Testing; Manufacturing operators perform sampling inspection of pouches sealed on identified sealing equipment during the work order process for product packaging and sealers used in each sterile load. Samples are obtained by the manufacturing operators during the manufacturing packaging process per the XPI or XII, the samples are then placed into cartons marked QA Package Test Samples, and included with each sterile load prior to sterilization process Each QA Package Test Samples are comprised of a minimum of 5 (five) sample pouches, sealed lid packages, or other sealed package obtained from a Single work order during the course of manufacturing and packaging per the XPI or XII. Carton and label samples with the Work Order #, Sealing Equipment #, product # and pouch # or pouch/package size, date and time selected for test sampling on QCFM Sampling plan for test package and subsequent product functional sample testing is derived from ANSI/ASQZ 1.4 as justified by the pre-sterilization testing on seal integrity. This QA final sampling of (five minimum) selected test samples from the identified sealer equipment is an audit to observe any changes in MI and II attributes after sterilization and confirms product suitability for QA final release Prior to load final release, QA is delivered the QA Package Test Samples and QCFM 067. QA shall verify Load Number, Purchase Order, Packing List, Sterilization Certification per SOP 389 for Gamma or SOP 582 for E-Beam Testing and Inspection: Test results are documented on QCFM 067 to record the selected test sample, identify the Work Order/Lot #, Sealer Equipment I.D. #, product #, description/family #, and pouch #/tray # or pouch/package size. QCFM 067 shall be retained with the load release packet Packaging Visual Testing: For each sterile load containing any identified Product Family types in Table 3, QA selects a minimum of 5 (five) random finished units (products within pouches / seals packages), of a minimum of 1 identified product from each of the Product Family types. QA individually inspects the package seals for any physical / functional defects, i.e., tears, ruptured seals, holes, voids, or channels, contamination, etc After sterilization, packaging seals are no longer considered in-process. Certain seal defects (as shown in Figure 1 for pouches and Figure 2 for trays) may be acceptable provided a minimum of 1/8 of uninterrupted seal remains; however, this is at the discretion of Quality Engineering and Packaging Engineering following investigation Packaging Functional Testing: For each sterile load containing any identified Product Family types in Table 3, QA selects a minimum of 5 (five) random finished units (products within pouches / seals packages), of a minimum of 1 identified product from each of the Product Family types QA conducts destructive testing (ARO Burst Test per section 5.1.1, and Peel Test per section 5.2.1) of each identified Product Family types samples in accordance to the MI, II, or XPI for the product Product Visual and Functional Testing: Finished product units of use for functional testing can be obtained from the packaging samples. QA conducts destructive testing of samples per Table 3 below and in accordance to the MI, II, or XPI for the product Functional Test for Vari-stim III Post Sterile EO Ensure that LED lights on each of the three settings when contact is made between needle and probe Functional Test for Pulsatron II Post Sterile EO Ensure that LED lights when contact is made between needle and probe when button is depressed.

27 Rev. BO BP Ref. 7.1 Page 13 of 14 Table 3: Post-Sterilization Functional Product Family Test Table Family Number Product Family Typical Product # Description Product Testing Required 1 Pulsatron Yes 2 Vari-Stim III Yes Special Case Products Sterilized at Back Up Sterilizer: In the event a load is sent to Medtronic Xomed s emergency backup sterilizer, SSG in Atlanta, Georgia, QA shall inspect the load list upon arrival back from vendor to ensure restricted products were not sterilized at SSG. The restricted products and their product numbers (P/Ns) are Hydrodebrider (P/Ns and ), International EMG Tubes (P/Ns , , , , , and ), and NIM TriVantage EMG Tubes (P/Ns , , , , , , , , , and ). Upon inspection if said P/Ns are present on load list, fill out the appropriate section of QCFM 067, and pull product(s) from the load, quantity verified with load list, and dispositioned through the NCMR process.

28 Rev. BO BP Ref. 7.1 Page 14 of 14 Attachment A: Minimum Burst Value Calculation 1. Minimum Burst Values for pouches are derived from the formula: Burst Pressure = (Perimeter) x 454 OR 2 (L + W) x 454 OR (Inner Seal Perimeter) x 454 (Area) x (L x W) x (Area of Inner Seal) x Where: L = inner length of seal W = inner width of seal For pouches with a Side A material of Tyvek 1059, multiply final value derived from formula above by 0.75 to obtain minimum burst value. For pouches with a Side B material of Nylon, multiply final value derived from formula above by 0.75 to obtain minimum burst value. This formula also applies to tray seals. Perimeter and Area were measured using the following diagrams: CHEVRON POUCH CORNER CUT POUCH Perimeter = 2P + 2R + J Perimeter = 2P + S + T + R + J Area = (P x J) + [O x (J/2)] Area = (P x J) + (S x T) + [S x (U/2)] 2. Burst test formula derived from Thomas P. Wachala article Correlating Tensile & Burst Tests in Pouches from 1991 edition of Medical Device & Diagnostic Industry. 3. Minimum burst value correlates to minimum tensile value for seal strength. Industry practice prescribes a minimum tensile value of 0.75 to 1.0 (lbf) pounds of force based on material. 4. The burst values calculated are provided as a minimum requirement. Process validation for heat sealers is required per SOP 327.