XenoSure Biologic Patch

K190882 · Lemaitre Vascular · PSQ · Feb 13, 2020 · Cardiovascular

Device Facts

• Record ID: K190882
• Device Name: XenoSure Biologic Patch
• Applicant: Lemaitre Vascular
• Product Code: PSQ · Cardiovascular
• Decision Date: Feb 13, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 870.3470
• Device Class: Class 2
• Attributes: Therapeutic

Intended 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.

Device Story

XenoSure Biologic Patch consists of bovine pericardial tissue treated with glutaraldehyde to crosslink collagen and minimize antigenicity. Device is used by surgeons in cardiovascular and general surgical procedures for tissue reconstruction, repair, and suture line reinforcement. Subject device is modified to allow storage at temperatures below 0°C by underfilling the packaging to accommodate solution expansion upon freezing. Device is supplied in a jar with sterile glutaraldehyde storage solution. Clinical benefit includes providing a biocompatible, durable patch material for surgical repair. Performance is verified through bench testing (tensile, burst, suture retention, permeability) and in-vivo animal studies comparing frozen vs. non-frozen patches to ensure safety and efficacy remain equivalent to the predicate.

Clinical Evidence

Prospective animal study (n=7 Polypay sheep) compared frozen vs. non-frozen patches implanted in carotid arteries. Primary endpoints included vessel patency, local tissue response, endothelialization, and tissue integration over 90 days. Results showed no significant differences between groups; both achieved appropriate sealing and favorable tissue responses. Bench testing confirmed mechanical properties (tensile, suture retention, etc.) were statistically equivalent or clinically acceptable.

Technological Characteristics

Bovine pericardium tissue; glutaraldehyde cross-linked; chemically sterilized per ISO 14160:2011; packaged in jar with glutaraldehyde storage solution. Modified for freeze-tolerance via underfilled packaging. No changes to material composition or design compared to predicate.

Indications for Use

Indicated for cardiac and vascular reconstruction and repair, soft tissue deficiency repair, and suture line reinforcement during general surgical procedures in patients requiring such surgical intervention.

Regulatory Classification

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.

Predicate Devices

• XenoSure Biologic Patch (K040835)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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) Zhang<br>VP of Regulatory Affairs<br>LeMaitre Vascular, Inc.<br>Email: [e-mail] |
| 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 |
| Establishment<br>Registration: | 1220948 |
| Establishment: | 63 Second Avenue<br>Burlington, MA 01803 |
| Predicate Device: | XenoSure Biologic Patch (K040835) |
| Reference Device: | None |
| Device Description: | The XenoSure consists of one piece of bovine pericardial<br>tissue that has been selected for minimal tissue blemishes.<br>The tissue is treated with a glutaraldehyde process which<br>crosslinks the collagen fibers and minimizes antigenicity.<br>XenoSure patch is liquid chemical sterilized and packaged<br>in a plastic jar containing sterile glutaraldehyde storage<br>solution. |

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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. | | | |
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| Summary of Technological<br>Characteristics: | 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 for<br>Use | The XenoSure® Biologic Patch<br>is intended for use as a surgical<br>patch material for cardiac and<br>vascular reconstruction and<br>repair, soft tissue deficiency<br>repair and reinforcing the suture<br>line during general surgical<br>procedures. | | The XenoSure® Biologic Patch<br>is intended for use as a surgical<br>patch material for cardiac and<br>vascular reconstruction and<br>repair, soft tissue deficiency<br>repair and reinforcing the suture<br>line during general surgical<br>procedures. | 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 |
| Medical<br>Specialists | 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 that<br>XenoSure biologic patch (frozen) meets the product<br>performance requirements of the device specifications and<br>does not raise any additional safety issues. | | | |
| Sterilization: | XenoSure biologic patch is chemically sterilized<br>according to ISO14160: 2011, “Sterilization of health care<br>products -- Liquid chemical sterilizing agents for single-<br>use medical devices utilizing animal tissues and their<br>derivatives -- Requirements for characterization,<br>development, validation and routine control of a<br>sterilization process for medical devices”. | | | |
| Biocompatibility: | The material for XenoSure Biologic Patch is bovine<br>pericardium. It is identical to that in the predicate device<br>which has established biocompatibility. There is no<br>change to the materials, manufacturing process, or<br>packaging for this submission and the biocompatibility is<br>not affected. | | | |
| Summary of Product Testing: | The following tests have been completed on baseline and<br>aged product to evaluate the XenoSure Biologic Patch<br>(frozen) in comparison to the predicate device (unfrozen<br>patch):<br>• Longitudinal Tensile test<br>• Burst strength test<br>• Suture retention test<br>• Water Permeability<br>• Elongation<br>• Cross Linking test<br>• Collagenase digestion<br>• Delamination | | | |
| Test | Test method summary | Results | | |
| Longitudinal<br>Tensile | Use Instron pull the sample until it<br>fails. Record the ultimate tensile<br>strength in MPa. | All XenoSure patches passed the acceptance<br>criteria of ≥ 2 MPa. The mean of tensile strength<br>of the predicate device (unfrozen) was measured<br>as 12.9 MPa. The mean of tensile strength of<br>XenoSure patch (frozen) was measured as 12.1<br>MPa. There is no statistical difference. | | |
| Elongation | Use Instron pull the sample until it<br>fails. Record the elongation at the<br>failure as percent of the original sample<br>length. | All XenoSure patches passed the acceptance<br>criteria of 5~50% elongation. The mean of<br>elongation of the predicate device was measured<br>as 21.8%. The mean of elongation of XenoSure<br>patch (frozen) was measured as 22.3%. There is<br>no statistical difference. | | |

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| Burst strength | Sample is secured in the testing fixture<br>as a membrane between two chambers.<br>One side of the sample is slowly<br>pressurized using water. Record the<br>pressure at the time of burst or leak. | All XenoSure patches passed the acceptance<br>criteria of ≥ 12 PSI. The mean of burst strength<br>of the predicate device (unfrozen patch) was<br>measured as 134 PSI. The mean of burst strength<br>of XenoSure patch (frozen) was measured as<br>113 PSI. They are statistically different.<br>However, since both results are much higher<br>than the clinical specification of 12PSI, the<br>difference does not have any clinical<br>significance. |
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| Suture retention | Make sutures on the edge of the patch.<br>Pull the suture using Instron until either<br>patch or suture fail. Record the force at<br>the failure. | All XenoSure patches passed the acceptance<br>criteria of ≥ 300 gf. The mean of suture retention<br>of the predicate device was measured as 1233 gf.<br>The mean of suture retention of XenoSure patch<br>(frozen) was measured as 1235 gf. There is no<br>statistical difference. |
| Cross Linking | This test is to determine the degree of<br>cross-linking of collagen based<br>materials by measuring the amounts of<br>unreacted amino groups. Free amino<br>groups will bind to<br>2,4,6-trinitrobenzenesulfonic acid<br>(TNBS) and the remaining TNBS is<br>reacted with glycine to<br>produce a complex that absorbs<br>strongly at 340 nm and can be<br>quantitatively measured by UV-Vis<br>Spectrophotometry. The number of free<br>amine sites is calculated using a pre-<br>and post-test calibration curve and the<br>absorbance of the test sample. | There is no acceptance criteria for this test. The<br>cross linking of the predicate (unfrozen patch) is<br>29 ppm free amine site per gram. The cross<br>linking of the proposed (frozen) patch is 28 ppm<br>free amine site per gram. The test results show<br>there is no statistical difference between the<br>proposed and predicate devices. |
| Collagenase<br>Digestion | This test is to determine the digestion<br>rates of biological tissue by collagenase<br>digestion. Collagenase will cleave<br>glycine bonds in collagen, breaking<br>tissue down into peptides. Depending<br>on the type of tissue and crosslinking<br>used, the biologic tissues can exhibit<br>different digestion rates. | There is no acceptance criteria for this test. The<br>digestion of the predicate (unfrozen patch) is<br>0.16%. The digestion of the proposed (frozen<br>patch) is 0.18%. The test results show there is no<br>statistical difference between the proposed and<br>predicate devices. |
| Water<br>Permeability | This test is to measure the water<br>permeability of the tissue under 120<br>mmHg pressure. | The acceptance criteria is < 0.1 ml/cm2 min<br>All samples for both predicate and proposed<br>devices recorded zero water permeability and<br>therefore are not statistically different. |
| Delamination | This is a visual inspection. The<br>operator inspects the patch for<br>delamination. | No delamination was identified for both the<br>predicate and proposed devices. |

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| Summary of Pre-clinical Study: | The objective of this study was to evaluate the safety of a<br>previously frozen XenoSure Biologic Vascular Patch (test<br>patch) in comparison to a non-frozen XenoSure<br>Biologic Vascular Patch (control/predicate patch).<br>Seven Polypay sheep underwent a single surgical<br>procedure on Day 0, in which bilateral vascular patches<br>were implanted following an arteriotomy and animals<br>were recovered for 90 days. The previously frozen<br>XenoSure Biologic Vascular Patch (test) was implanted in<br>one carotid artery and the non-frozen XenoSure Biologic<br>Vascular Patch (control) was implanted<br>in the opposite carotid artery, for each animal. Activated<br>clotting times were monitored during the surgical<br>procedure. Aspirin was administered for antiplatelet<br>therapy at least once every 5 days until euthanasia.<br>Angiographic assessments were performed on Day 0<br>(before and after patch implant completion) and before<br>necropsy. Ultrasound was also performed on Day 0 after<br>carotid artery skin incision closure, at interim time points,<br>and prior to necropsy. Animal health was monitored via<br>incision site and clinical observations, body<br>weights/condition and clinical pathology, at pre-<br>determined, regular intervals. On Days 89-90 the animals<br>were euthanized and comprehensive necropsies were<br>performed. The patch-implanted carotid arteries were<br>collected and processed for histopathologic evaluation.<br>Additionally, representative tissues/organs were collected<br>and will be archived with the study materials.<br>Six of seven animals survived to the scheduled time point.<br>Following implantation, all carotid patches were noted to<br>achieve appropriate sealing (i.e., there were no leaks) prior<br>to closure. One animal was euthanized on Day 21 due to<br>poor prognosis after chronic inappetance and observation<br>of pale conjunctiva and mucous membranes. Early<br>euthanasia of the animal was interpreted to be unrelated to<br>the carotid patches themselves. Both test and control<br>carotid patches did not affect vessel patency based on<br>angiography and ultrasound analysis. Histologically,<br>implantation of the previously frozen XenoSure Biologic<br>Vascular Patch was associated with favorable local tissue<br>responses (such as endothelialization, tissue integration<br>and absence of adverse effects) that were comparable to<br>those seen with the control device, nonfrozen XenoSure<br>Biologic Vascular Patch. Statistical comparison between<br>treatment groups showed no significant differences<br>between any of the compared histologic parameters<br>associated with the bovine pericardium patches.<br>Overall, the previously frozen XenoSure Biologic<br>Vascular Patch (test patch) displayed bioequivalence and<br>comparable characteristics in vascular safety, local tissue<br>response, endothelialization, and tissue integration to the<br>non-frozen XenoSure Biologic Vascular Patch<br>(control/predicate patch). |
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| Conclusion: | LeMaitre Vascular has demonstrated that XenoSure<br>Biologic Patch (frozen) is substantially equivalent to the<br>predicate device (unfrozen patch) based on its intended<br>use and fundamental scientific technology. |
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