(315 days)
The XenoSure Biologic Patch is intended for use as a surgical patch material for cardiac reconstruction and repair, soft tissue deficiency repair and reinforcing the suture line during general surgical procedures.
The XenoSure consists of one piece of bovine pericardial tissue that has been selected for minimal tissue blemishes. The tissue is treated with a glutaraldehyde process which crosslinks the collagen fibers and minimizes antigenicity. XenoSure patch is liquid chemical sterilized and packaged in a plastic jar containing sterile glutaraldehyde storage solution.
The provided text is a 510(k) summary for the XenoSure Biologic Patch, which is a medical device. This document details the pre-clinical testing performed to demonstrate substantial equivalence to a predicate device, specifically to support a labeling change allowing the device to be exposed to temperatures below 0°C (i.e., frozen).
The request asks for information typically associated with the acceptance criteria and proof of performance for an AI/ML-driven medical device, including aspects like human reader studies, training/test set sample sizes, and ground truth establishment by experts. However, the provided document does not describe an AI/ML device; it is for a physical biologic patch used as surgical material. Therefore, information about AI-specific aspects (like MRMC studies, human-in-the-loop performance, training/test set ground truth for AI, number of experts for ground truth, etc.) is not applicable to this document.
Instead, the document details laboratory and animal studies to prove the physical and biological characteristics of the XenoSure Biologic Patch are not adversely affected by freezing.
Here's an analysis of the provided text in the context of the device's performance and acceptance criteria:
Acceptance Criteria and Study for XenoSure Biologic Patch
The study described here aims to demonstrate that a frozen XenoSure Biologic Patch is substantially equivalent to the unfrozen predicate XenoSure Biologic Patch. The acceptance criteria are based on mechanical properties and biological performance, ensuring the frozen device retains its intended function and safety.
1. Table of Acceptance Criteria and Reported Device Performance:
| Test | Acceptance Criteria | Reported Device Performance (Frozen Device) |
|---|---|---|
| Longitudinal Tensile | ≥ 2 MPa | Mean tensile strength: 12.1 MPa. All patches passed. No statistical difference from unfrozen predicate (12.9 MPa). |
| Elongation | 5% - 50% elongation | Mean elongation: 22.3%. All patches passed. No statistical difference from unfrozen predicate (21.8%). |
| Burst Strength | ≥ 12 PSI | Mean burst strength: 113 PSI. All patches passed. Statistically different from unfrozen predicate (134 PSI), but the difference is not clinically significant as both are much higher than the 12 PSI clinical specification. |
| Suture Retention | ≥ 300 gf | Mean suture retention: 1235 gf. All patches passed. No statistical difference from unfrozen predicate (1233 gf). |
| Cross Linking | No acceptance criteria stated for this test, but comparison to predicate is implicit for substantial equivalence. | 28 ppm free amine site per gram. No statistical difference from unfrozen predicate (29 ppm free amine site per gram). |
| Collagenase Digestion | No acceptance criteria stated for this test, but comparison to predicate is implicit for substantial equivalence. | 0.18%. No statistical difference from unfrozen predicate (0.16%). |
| Water Permeability | < 0.1 ml/cm² min | All samples for both predicate and proposed (frozen) devices recorded zero water permeability. No statistical difference. |
| Delamination (Visual Inspection) | No delamination | No delamination identified for both predicate and proposed (frozen) devices. |
| In-vivo Animal Study (Safety & Comparability) | Favorable local tissue responses (e.g., endothelialization, tissue integration, absence of adverse effects) comparable to control device; no effect on vessel patency; bioequivalence. | Six of seven animals survived the full 90-day duration. One animal's early euthanasia was unrelated to the patches. All carotid patches achieved appropriate sealing (no leaks). Both test (frozen) and control (unfrozen) patches did not affect vessel patency based on angiography and ultrasound. Histologically, the frozen patches showed favorable local tissue responses comparable to the control, with no significant differences in histological parameters. Displayed bioequivalence and comparable characteristics in vascular safety, local tissue response, endothelialization, and tissue integration. |
2. Sample Sizes and Data Provenance:
-
Test Set (Physical Properties):
- Specific numbers of samples tested for each physical property (e.g., tensile strength, burst strength) are not explicitly stated in the summary, but the results indicate that "All XenoSure patches" or "All samples for both predicate and proposed devices" were tested and passed, implying a sufficient sample size was used for each test to demonstrate statistical equivalence or compliance with criteria.
- Data Provenance: The tests are laboratory-based, performed on the manufactured device. The document does not specify the country of origin of the data, but it is for a US FDA submission, implying adherence to relevant standards for medical device testing. The studies are pre-clinical performance testing.
-
Test Set (In-vivo Animal Study):
- Sample Size: Seven Polypay sheep (6 survived to the scheduled time point). Each animal received both a frozen (test) and unfrozen (control) patch, allowing for within-subject comparison.
- Data Provenance: The study was conducted in animals, a pre-clinical, prospective study design. The country of origin of the animal study isn't specified, but it was performed to support a US FDA submission.
3. Number of Experts and Qualifications for Ground Truth:
- Not applicable for an AI/ML device. For this physical device, "ground truth" is established through standardized laboratory testing methods (e.g., Instron for mechanical properties, spectrophotometry for chemical properties) and histological analysis by qualified veterinary pathologists in the animal study. The document does not specify the number or qualifications of individuals interpreting the histology, but it is standard for such studies to involve board-certified pathologists.
4. Adjudication Method:
- Not applicable for an AI/ML device. For the physical testing, the results are quantitative measurements or visual inspections against defined criteria. For the animal study, histological evaluation would typically follow a standardized protocol, often with consensus or independent review by pathologists, but no formal "adjudication method" in the sense of reader disagreements for an AI study is described.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- Not applicable. This device is a physical patch, not an AI system. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed.
6. Standalone Performance (Algorithm Only):
- Not applicable. This pertains to an AI algorithm. The device is a physical biologic patch. The "standalone performance" of the device is assessed through the physical and biological tests described in the table above.
7. Type of Ground Truth Used:
- Laboratory Measurements: For mechanical and chemical properties, the "ground truth" is derived from direct quantitative measurements using validated test methods (e.g., Instron for force, UV-Vis Spectrophotometry for chemical levels).
- Visual Inspection: For delamination, ground truth is established by direct visual inspection.
- In-vivo Histopathology and Clinical Outcomes: For the animal study, the "ground truth" for safety and biological integration is based on gross observations, angiographic and ultrasound analysis of vessel patency, and detailed histopathologic evaluation of explanted tissues by qualified personnel.
8. Sample Size for Training Set:
- Not applicable. There is no "training set" as this is not an AI/ML device.
9. How Ground Truth for Training Set was Established:
- Not applicable. There is no "training set" for this physical medical device.
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February 13, 2020
LeMaitre Vascular John Bradsher Senior Regulatory Affairs Specialist 63 Second Avenue Burlington, Massachusetts 01803
Re: K190882
Trade/Device Name: XenoSure Biologic Patch Regulation Number: 21 CFR 870.3470 Regulation Name: Intracardiac Patch Or Pledget Made Of Polypropylene, Polyethylene Terephthalate, Or Polytetrafluoroethylene Regulatory Class: Class II Product Code: PSQ Dated: April 2, 2019 Received: April 4, 2019
Dear John Bradsher:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Rachel Neubrander, Ph.D. Assistant Director DHT2B: Division of Circulatory Support, Structural and Vascular Devices OHT2: Office of Cardiovascular Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K190882
Device Name XenoSure Biologic Patch
Indications for Use (Describe)
The XenoSure Biologic Patch is intended for use as a surgical patch material for cardiac reconstruction and repair, soft tissue deficiency repair and reinforcing the suture line during general surgical procedures.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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K190882 510k Summary
| Submitter's Information | |
|---|---|
| Name: | LeMaitre Vascular, Inc. |
| Address: | 63 Second Avenue, Burlington, MA 01803 |
| Phone: | 781-425-1706 |
| Fax: | 781-425-5049 |
| Contact Person: | Xiang (Vic) ZhangVP of Regulatory AffairsLeMaitre Vascular, Inc.Email: xzhang@lemaitre.com |
| Date Prepared: | February 13, 2020 |
| Device Name: | XenoSure Biologic Patch |
| Trade Name: | XenoSure Biologic Patch |
| Common Name: | Intracardiac patch or pledget |
| Regulation Number: | 21 CFR 870.3470 |
| Classification Panel: | Cardiovascular |
| Class: | II (2) |
| Product Code: | PSQ |
| EstablishmentRegistration: | 1220948 |
| Establishment: | 63 Second AvenueBurlington, MA 01803 |
| Predicate Device: | XenoSure Biologic Patch (K040835) |
| Reference Device: | None |
| Device Description: | The XenoSure consists of one piece of bovine pericardialtissue that has been selected for minimal tissue blemishes.The tissue is treated with a glutaraldehyde process whichcrosslinks the collagen fibers and minimizes antigenicity.XenoSure patch is liquid chemical sterilized and packagedin a plastic jar containing sterile glutaraldehyde storagesolution. |
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| Indication for Use: | The XenoSure Biologic Patch is intended for use as a surgical patch material for cardiac and vascular reconstruction and repair, soft tissue deficiency repair and reinforcing the suture line during general surgical procedures. | |||
|---|---|---|---|---|
| Summary of TechnologicalCharacteristics: | The purpose of this submission is to support the labeling change of removing the warning that XenoSure cannot be frozen. No change to the device design, materials, packaging materials, or manufacturing processes. The only change is to underfill the final package to tolerate the expected expansion if the storage solution is frozen. Comparisons of the XenoSure Biologic Patch (frozen) with the predicate XenoSure Biologic Patch (unfrozen) show that technological characteristics such as materials, biocompatibility, performance, and sterilization of the proposed device are substantially equivalent to the predicate device. The difference between the proposed device and the predicate device is the proposed device labeling will allow the device to be exposed to temperature below 0°C while the predicate device labeling warns against that. For the subject device, the storage solution is under-filled to accommodate potential frozen expansion. This difference was evaluated to demonstrate substantial equivalence via performance testing and an in-vivo animal study. | |||
| Proposed Device | Predicate Device | Comparison | ||
| Product Name: | Product Name: | |||
| XenoSure Biologic Patch | XenoSure Biologic Patch | |||
| Manufacturer | LeMaitre Vascular Inc. | LeMaitre Vascular Inc. | Same | |
| Clearance | This submission | K040835 | ||
| Indications forUse | The XenoSure® Biologic Patchis intended for use as a surgicalpatch material for cardiac andvascular reconstruction andrepair, soft tissue deficiencyrepair and reinforcing the sutureline during general surgicalprocedures. | The XenoSure® Biologic Patchis intended for use as a surgicalpatch material for cardiac andvascular reconstruction andrepair, soft tissue deficiencyrepair and reinforcing the sutureline during general surgicalprocedures. | Same | |
| Materials | Bovine pericardium | Bovine pericardium | Same | |
| Design | Various size patches | Various size patches | Same | |
| Sterility | Chemical sterilization with 10-6 SAL | Chemical sterilization with 10-6 SAL | Same | |
| Single Use | Yes | Yes | Same | |
| MedicalSpecialists | Cardiovascular | Cardiovascular | Same | |
| Packaging | Jar/Lid, carton | Jar/Lid, carton | Same | |
| Shelf Life | 6 years | 6 years | Same | |
| Functional/Safety Testing: | The verification activities conducted indicate thatXenoSure biologic patch (frozen) meets the productperformance requirements of the device specifications anddoes not raise any additional safety issues. | |||
| Sterilization: | XenoSure biologic patch is chemically sterilizedaccording to ISO14160: 2011, “Sterilization of health careproducts -- Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and theirderivatives -- Requirements for characterization,development, validation and routine control of asterilization process for medical devices”. | |||
| Biocompatibility: | The material for XenoSure Biologic Patch is bovinepericardium. It is identical to that in the predicate devicewhich has established biocompatibility. There is nochange to the materials, manufacturing process, orpackaging for this submission and the biocompatibility isnot affected. | |||
| Summary of Product Testing: | The following tests have been completed on baseline andaged product to evaluate the XenoSure Biologic Patch(frozen) in comparison to the predicate device (unfrozenpatch):• Longitudinal Tensile test• Burst strength test• Suture retention test• Water Permeability• Elongation• Cross Linking test• Collagenase digestion• Delamination | |||
| Test | Test method summary | Results | ||
| LongitudinalTensile | Use Instron pull the sample until itfails. Record the ultimate tensilestrength in MPa. | All XenoSure patches passed the acceptancecriteria of ≥ 2 MPa. The mean of tensile strengthof the predicate device (unfrozen) was measuredas 12.9 MPa. The mean of tensile strength ofXenoSure patch (frozen) was measured as 12.1MPa. There is no statistical difference. | ||
| Elongation | Use Instron pull the sample until itfails. Record the elongation at thefailure as percent of the original samplelength. | All XenoSure patches passed the acceptancecriteria of 5~50% elongation. The mean ofelongation of the predicate device was measuredas 21.8%. The mean of elongation of XenoSurepatch (frozen) was measured as 22.3%. There isno statistical difference. |
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| Burst strength | Sample is secured in the testing fixtureas a membrane between two chambers.One side of the sample is slowlypressurized using water. Record thepressure at the time of burst or leak. | All XenoSure patches passed the acceptancecriteria of ≥ 12 PSI. The mean of burst strengthof the predicate device (unfrozen patch) wasmeasured as 134 PSI. The mean of burst strengthof XenoSure patch (frozen) was measured as113 PSI. They are statistically different.However, since both results are much higherthan the clinical specification of 12PSI, thedifference does not have any clinicalsignificance. |
|---|---|---|
| Suture retention | Make sutures on the edge of the patch.Pull the suture using Instron until eitherpatch or suture fail. Record the force atthe failure. | All XenoSure patches passed the acceptancecriteria of ≥ 300 gf. The mean of suture retentionof the predicate device was measured as 1233 gf.The mean of suture retention of XenoSure patch(frozen) was measured as 1235 gf. There is nostatistical difference. |
| Cross Linking | This test is to determine the degree ofcross-linking of collagen basedmaterials by measuring the amounts ofunreacted amino groups. Free aminogroups will bind to2,4,6-trinitrobenzenesulfonic acid(TNBS) and the remaining TNBS isreacted with glycine toproduce a complex that absorbsstrongly at 340 nm and can bequantitatively measured by UV-VisSpectrophotometry. The number of freeamine sites is calculated using a pre-and post-test calibration curve and theabsorbance of the test sample. | There is no acceptance criteria for this test. Thecross linking of the predicate (unfrozen patch) is29 ppm free amine site per gram. The crosslinking of the proposed (frozen) patch is 28 ppmfree amine site per gram. The test results showthere is no statistical difference between theproposed and predicate devices. |
| CollagenaseDigestion | This test is to determine the digestionrates of biological tissue by collagenasedigestion. Collagenase will cleaveglycine bonds in collagen, breakingtissue down into peptides. Dependingon the type of tissue and crosslinkingused, the biologic tissues can exhibitdifferent digestion rates. | There is no acceptance criteria for this test. Thedigestion of the predicate (unfrozen patch) is0.16%. The digestion of the proposed (frozenpatch) is 0.18%. The test results show there is nostatistical difference between the proposed andpredicate devices. |
| WaterPermeability | This test is to measure the waterpermeability of the tissue under 120mmHg pressure. | The acceptance criteria is < 0.1 ml/cm2 minAll samples for both predicate and proposeddevices recorded zero water permeability andtherefore are not statistically different. |
| Delamination | This is a visual inspection. Theoperator inspects the patch fordelamination. | No delamination was identified for both thepredicate and proposed devices. |
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| Summary of Pre-clinical Study: | The objective of this study was to evaluate the safety of apreviously frozen XenoSure Biologic Vascular Patch (testpatch) in comparison to a non-frozen XenoSureBiologic Vascular Patch (control/predicate patch).Seven Polypay sheep underwent a single surgicalprocedure on Day 0, in which bilateral vascular patcheswere implanted following an arteriotomy and animalswere recovered for 90 days. The previously frozenXenoSure Biologic Vascular Patch (test) was implanted inone carotid artery and the non-frozen XenoSure BiologicVascular Patch (control) was implantedin the opposite carotid artery, for each animal. Activatedclotting times were monitored during the surgicalprocedure. Aspirin was administered for antiplatelettherapy at least once every 5 days until euthanasia.Angiographic assessments were performed on Day 0(before and after patch implant completion) and beforenecropsy. Ultrasound was also performed on Day 0 aftercarotid artery skin incision closure, at interim time points,and prior to necropsy. Animal health was monitored viaincision site and clinical observations, bodyweights/condition and clinical pathology, at pre-determined, regular intervals. On Days 89-90 the animalswere euthanized and comprehensive necropsies wereperformed. The patch-implanted carotid arteries werecollected and processed for histopathologic evaluation.Additionally, representative tissues/organs were collectedand will be archived with the study materials.Six of seven animals survived to the scheduled time point.Following implantation, all carotid patches were noted toachieve appropriate sealing (i.e., there were no leaks) priorto closure. One animal was euthanized on Day 21 due topoor prognosis after chronic inappetance and observationof pale conjunctiva and mucous membranes. Earlyeuthanasia of the animal was interpreted to be unrelated tothe carotid patches themselves. Both test and controlcarotid patches did not affect vessel patency based onangiography and ultrasound analysis. Histologically,implantation of the previously frozen XenoSure BiologicVascular Patch was associated with favorable local tissueresponses (such as endothelialization, tissue integrationand absence of adverse effects) that were comparable tothose seen with the control device, nonfrozen XenoSureBiologic Vascular Patch. Statistical comparison betweentreatment groups showed no significant differencesbetween any of the compared histologic parametersassociated with the bovine pericardium patches.Overall, the previously frozen XenoSure BiologicVascular Patch (test patch) displayed bioequivalence andcomparable characteristics in vascular safety, local tissueresponse, endothelialization, and tissue integration to thenon-frozen XenoSure Biologic Vascular Patch(control/predicate patch). |
|---|---|
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| Conclusion: | LeMaitre Vascular has demonstrated that XenoSureBiologic Patch (frozen) is substantially equivalent to thepredicate device (unfrozen patch) based on its intendeduse and fundamental scientific technology. |
|---|---|
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§ 870.3470 Intracardiac patch or pledget made of polypropylene, polyethylene terephthalate, or polytetrafluoroethylene.
(a)
Identification. An intracardiac patch or pledget made of polypropylene, polyethylene terephthalate, or polytetrafluoroethylene is a fabric device placed in the heart that is used to repair septal defects, for patch grafting, to repair tissue, and to buttress sutures.(b)
Classification. Class II (performance standards).