Cova™ORTHO-NERVE is a pure collagen membrane designed to be used as a barrier to allow guided healing along distinct anatomical planes. It is completely resorbable within a time frame that is compatible with healing. The membrane is obtained by standardized, controlled manufacturing processes. Cova™ORTHO-NERVE is further sterilized in double-pouches by gamma-irradiation. Cova™ORTHO-NERVE membranes are designed to be resorbable, non inflammatory and biocompatible for uses to treat peripheral nerve injuries. When wetted, the membrane is conformable, elastic and easy to handle. It can be used alone or, if needed, it can be sutured in place. Cova™ORTHO-NERVE is provided in rectangular sheets of 15 x 25 mm, 20 x 30 mm, 30 x 40 mm and 40 x 60 mm. Furthermore, the device can be easily trimmed or shaped to the appropriate size, without tearing or fragmenting, to fit the zone to be treated.

AI/ML Overview

This document describes a 510(k) premarket notification for the Cova™ORTHO-NERVE, a resorbable collagen membrane for peripheral nerve repair. The submission focuses on demonstrating substantial equivalence to predicate devices rather than proving performance against specific acceptance criteria for a novel device. Therefore, a table of acceptance criteria and reported device performance from a clinical study is not applicable in this context. The information provided relates to non-clinical data, bench tests, and animal studies to demonstrate safety and effectiveness.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

As this is a 510(k) submission demonstrating substantial equivalence to predicate devices, specific acceptance criteria for a novel device performance claim (e.g., a specific sensitivity/specificity for an AI algorithm) are not presented in the document. Instead, the "acceptance criteria" are implied by meeting the standards for biocompatibility, physical characteristics, and safety established by the predicate devices and relevant ISO standards.

Test Category	Acceptance Criteria (Implied by Predicate Equivalence & ISO)	Reported Device Performance (Cova™ORTHO-NERVE)
Biocompatibility	No cytotoxicity, sensitization, irritation, systemic toxicity, pyrogenicity, hemolytic activity, mutagenicity, or clastogenicity. Absorption within a compatible timeframe.	Non-cytotoxic, No evidence of sensitization, No evidence of irritation, No mortality or systemic toxicity, No material-mediated pyrogenicity, No hemolytic activity, No evidence of mutagenicity, No evidence of clastogenicity. Absorption by 13 weeks. No inflammation observed.
Implantation/Performance	Protection during nerve repair, no adverse tissue reaction, no fibrous peri-nervous tissue, no systemic toxicity.	Protection during nerve repair. No fibrous peri-nervous tissue observed after 3, 60, or 90 days. No adverse tissue reaction to the implant up to 13 weeks of implantation. No systemic toxicity.
Viral Inactivation	Reduction of final viral load to the limit of detection.	Demonstrated "that the inactivation steps reduced down the final viral load to the limit of detection."
Bench Tests	Meet similar specifications as predicate devices (e.g., color, odor, feel, dimensions, suture strength, tensile strength, pH, UV spectra purity, enzymatic degradation, swelling rate, compression, kinking, endotoxin limit).	"The following tests were performed and were found to meet the similar specifications as a predicate." (Specific values not provided, but deemed acceptable)
Animal Study (Performance & Safety)	Ability to confer a protective environment for the repaired nerve, no fibrous peri-nervous tissue, lowered time for re-intervention.	Demonstrated "its ability to confer a protective environment for the repaired nerve." "No fibrous peri-nervous tissue was observed after 3, 60 or 90 days." "Time for re-intervention was also lowered."

2. Sample Sizes Used for Test Set and Data Provenance

Biocompatibility Tests: The document does not explicitly state the sample sizes for each specific biocompatibility test (e.g., how many guinea pigs for sensitization, how many mice for systemic toxicity, how many rabbits for pyrogenicity). It only indicates the types of animals used for some tests.
Implantation/Absorption Study: Rats were used. The number of rats is not specified, but time points were 3 weeks, 30 days, and 90 days.
Implantation (Safety and Performance) Study: Rats were used. The number of rats is not specified, but time points were 3, 30, and 90 days.
Subchronic/Chronic Toxicity Study: Rats were used for a 13-week study. The number of rats is not specified.
Animal Study (Performance in nerve repair): A "rat model" was used. The specific number of rats or nerves involved is not provided.
Data Provenance: All studies (biocompatibility, implantation, animal study) appear to be preclinical (animal and in vitro) and were conducted by the manufacturer or contracted labs. The document does not specify the country of origin for the data beyond the manufacturer being in France. These are prospective non-clinical studies.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

This information is not applicable as the document describes a medical device (collagen membrane) and not an AI/imaging device requiring expert-established ground truth for a test set in the conventional sense. The "ground truth" for the non-clinical studies is determined by direct measurement, observation, and histological analysis by researchers/pathologists.

4. Adjudication Method for the Test Set

This information is not applicable for the reasons stated above.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

This information is not applicable as the document is for a physical medical implant, not an AI or imaging diagnostic device.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This information is not applicable as the document is for a physical medical implant, not an AI or imaging diagnostic device. There is no "algorithm" in the context of Cova™ORTHO-NERVE.

7. Type of Ground Truth Used

The "ground truth" for the studies described relies on:

Biochemical/Cellular Assays: For cytotoxicity, sensitization, pyrogenicity, hemolysis, genotoxicity.
Histopathology/Microscopic Examination: For implantation studies (inflammation, tissue reaction, absorption, fibrous tissue formation around nerves).
Direct Observation/Measurement: For physical bench tests (dimensional, tensile strength, pH, etc.).
Viral Load Measurement: For viral inactivation studies.
Functional Outcomes/Observation: In the animal study, the ability to confer protection and reduce re-intervention time.

8. Sample Size for the Training Set

This information is not applicable as there is no "training set" in the context of a physical medical device. The device's characteristics are inherent to its manufacturing process and material properties, not learned from a dataset.

9. How the Ground Truth for the Training Set Was Established

This information is not applicable for the reasons stated above.

Summary

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K103081

MAR - 2 2012

510(k) Summary

Submitter's name and address: Biom'Up S.A. 8. Allee Irene Joliot-Curie 69800, Saint-Priest, France

Contact person:

Valerie Centis. R&D Project Manager and Regulatory Affairs

Biom'Up S.A.S 8, Allee Irene Joliot-Curie 69800, Saint-Priest, France Phone: +33 (0)4 86 57 36 10 Fax: +33 (0)4 37 69 00 84 Email: regulatory.affairs@biomup.com

Date Summary was prepared:

Trade/Proprietary Name:

Classification Name: Product Code: Regulation Number: Device Classification:

Predicate Devices

March 2nd, 2012

Cova™ORTHO-NERVE

Nerve Cuff JXI 21 CFR 882.5275 Class II

Collagen Nerve Wrap (K060952) NeuraWrap™ (K041620) NeuroGen™ (K011168)

Device Description

Cova™ORTHO-NERVE membranes are designed to be resorbable, non inflammatory and biocompatible for uses to treat peripheral nerve injuries. When wetted, the membrane is conformable, elastic and easy to handle. It can be used alone or, if needed, it can be

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Image /page/1/Picture/0 description: The image shows the logo for "biom'up ADVANCED BIOMATERIALS". Above the company name is a graphic of a wave made up of small dots. The company name is in bold, and the words "ADVANCED BIOMATERIALS" are in a smaller font size.

sutured in place. Cova™ORTHO-NERVE is provided in rectangular sheets of 15 x 25 mm, 20 x 30 mm, 30 x 40 mm and 40 x 60 mm. Furthermore, the device can be easily trimmed or shaped to the appropriate size, without tearing or fragmenting, to fit the zone to be treated.

Intended Use

Cova™ORTHO-NERVE is indicated for the repair of peripheral nerve injuries in which there is no gap or where a gap closure can be achieved by flexion of the extremity.

Basis for Substantial Equivalence

The intended use, product design, composition, physical structure and target population of Cova™ORTHO-NERVE resorbable collagen membranes are substantially equivalent to the FDA cleared and legally marketed predicate devices Collagen Nerve Wrap (K060952), NeuraWrap™ (K041620) and NeuroGen™ (K011168). Similarities are presented in Table 1.

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Table 1. Comparison of Cova™ORTHO-NERVE with the predicate devices

Medical Device	Cova™ ORTHO-NERVE	Collagen Nerve Wrap	NeuraWrap™ Nerve Protector	NeuroGen™ Nerve Guide
510(k)Class	K103081 (tbd)JXI	K060952JXI	K041620JXI	K011168JXI
CompositionOrigin	Type I CollagenPorcine	Type I collagenBovine	Type I collagenBovine	Type I collagenBovine
Intended use	Indicated for the repair of peripheralnerve injuries in which there is no gapor where a gap closure can be achievedby flexion of the extremity.	Indicated for the management of peripheral nerveinjuries in which there has been no substantial loss ofnerve tissue and where gap closure can be achievedby flexion of the extremity.	Indicated for the management of peripheralnerve injuries in which there has been nosubstantial loss of nerve tissue.	Indicated for the repair of peripheral nervediscontinuities where gap closure can beachieved by flexion of the extremity.
Characteristics	Membrane, rollable if neededEasy to manipulateFlexibleSmoothWettableHemostaticCell-occlusive	Pre-rolled membraneEasy to manipulateFlexibleSmoothWettableHemostaticCell-occlusive	Pre-rolled membraneEasy to manipulateFlexibleSmoothWettableHemostaticCell-occlusive	TubularEasy to manipulateFlexibleSmoothWettableHemostaticCell-occlusive
Biocompatibility	Established	Established	Established	Established
Non-pyrogenic	Yes	Yes	Yes	Yes
Resorbable	Yes	Yes	Yes	Yes
Suturable	Yes	Yes	Yes	Yes
Sterilization	Gamma irradiation	Gamma irradiation	Ethylene Oxide (EtO)	Ethylene Oxide (EtO)
Reusable	Single-use	Single-use	Single-use	Single-use
Shelf-life	24 months	36 months	36 months	36 months
Packaging	Double-peel packages	Double-peel packages	Double-peel packages	Double-peel packages

ಗಾ

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Any differences in technological characteristics between the Cova™ORTHO-NERVE and the predicate devices do not raise any new issues of safety or efficacy. The performance and safety of the material used was evaluated. The collective results have demonstrated that the Cova™ORTHO-NERVE is substantially equivalent to the respective predicate devices with regard to safety and efficacy.

Summary of Non-Clinical Data

Biocompatibility

Biocompatibility tests were selected in accordance with ISO-10993 - 1 (Biological Evaluation of Medical Devices) guidelines for a permanent implant in contact with tissue/bone. All studies were conducted pursuant to 21 CFR, Part 58, Good Laboratory Practices. The table 2 provides a summary of the biocompatibility test results and conclusions.

Test	Test Method	Results
Cytotoxicity	ISO Direct contact CytotoxicityAssay	Non-cytotoxic
Sensitization	ISO Guinea pig Maximization Testwith device extracts (saline andsesame oil extracts)	No evidence of sensitization
Acute IntracutaneousReactivity	ISO Acute IntracutaneousReactivity Test in rabbits withdevice extracts (saline andsesame oil extracts)	No evidence of irritation
Acute Systemic Toxicity	ISO Acute Systemic Toxicity inMice with device extracts (salineand sesame oil extracts)	No mortality or evidence of systemictoxicity
Rabbit Pyrogen Study	USP Material-mediated RabbitPyrogen Test with saline extractof the device	No evidence of material-mediatedpyrogenicity
Hemolysis	Hemolysis Test by direct contactwith human red blood cells	No hemolytic activity
Genotoxicity	ISO Ames Mutagenicity Assaywith device extracts (saline andethanol extracts)	No evidence of mutagenicity
Genotoxicity	ISO Mouse bone marrowmicronucleus with device extracts(saline and sesame oil extracts)	No evidence of clastogenicity

Table 2: Biocompatibility Testing Summary for Cova™ORTHO-NERVE

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Implantation/Absorption	Subcutaneous implantation inrats	Absorption of material by 13 weeksNo inflammation observed
Implantation (safety andperformance)	In vivo safety and performancestudy in rats after 3, 30 and 90days	Protection during nerve repairNo fibrous peri-nervous tissue wasobserved after 3, 60 or 90 days.
Subchronic / chronictoxicity	13-Week systemic toxicity andlocal Tolerance Study in ratsfollowing subcutaneousimplantation	No adverse tissue reaction to theimplant up to 13 weeks ofimplantationNo systemic toxicity

Viral Inactivation Study

Viral Inactivation steps were validated for collagen extracted from tissues used in the manufacture of the membranes. For the validation, different viruses were selected according to their physico-chemical resistance and representativeness. The viral inactivation steps are routinely performed in process using appropriate treatment. It was demonstrated that the inactivation steps reduced down the final viral load to the limit of detection.

Bench Test

In vitro bench tests were conducted on final product to demonstrate the safety and effectiveness of the device, and to demonstrate that the device performs as it is intended. The following tests were performed and were found to meet the similar specifications as a predicate.

-Color, odor, feel Inspection
-Dimensional Inspection
-Edge Verification
Suture strength Verification -
-Tensile strength Verification
pH Verification
UV Spectra Verification to determine the purity of the raw material -
Enzymatic Degradation Verification .
-Swelling Rate Verification
-Compression and Kinking

Moreover, Endotoxin (Limulus Amebocyte Lysate Test) testing is routinely performed on the final device to conform to the endotoxin limit of 20 EU/device.

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Image /page/5/Picture/0 description: The image shows the logo for Biom'up Advanced Biomaterials. The logo features the word "biom'up" in a bold, sans-serif font, with the apostrophe slightly raised. Above the word is a wavy line made up of small, vertical lines that get progressively shorter towards the ends. Below the word is the text "ADVANCED BIOMATERIALS" in a smaller, sans-serif font.

Animal Study

An animal study was conducted in rat model to evaluate the performance and safety (local tissue effects) of the Cova"*ORTHO-NERVE membrane after nerve section and direct suture in the rat peroneal nerve. No fibrous peri-nervous tissue was observed after 3, 60 or 90 days. The membrane also demonstrated its ability to confer a protective environment for the repaired nerve. Time for re-intervention was also lowered.

Conclusion

Cova™ORTHO-NERVE Resorbable Collagen Membrane is substantially equivalent to its predicate devices: Collagen Nerve Wrap, NeuraWrap™ and NeuroGen™.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The eagle is positioned to the right of a circular seal that contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Room -WO66-G609 Silver Spring, MD 20993-0002

Biom'up Sas c/o Valerie Centis, Ph.D. R&D Project Manager and Regulatory Affairs 8, Allee Irene Joliot-Curie St-Priest, France 69800

MAR - 2 2012

Re: K103081

Trade/Device Name: Cova™ ORTHO-NERVE Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: December 21, 2011 Received: December 22, 2011

Dear Dr. Centis:

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 1 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. 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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Page 2 - Valerie Centis, Ph.D.

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 (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Quchan for

Malvina B. Eydelman, I Director Division of Ophthalmic, Neurological, and Ear. Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): 长 | 0 3 0 8 |

Cova™ORTHO-NERVE Device Name:

Indications for Use:

Indicated for the repair of peripheral nerve injuries in which there is no gap or where a gap closure can be achieved by flexion of the extremity.

Prescription Use _____________________________________________________________________________________________________________________________________________________________

AND/OR

Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) ૮ ઉન

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)

Division of Ophthalmic, Neurological and Ear, Nose and Throat Devices

510(k) Number K103081

Page 1 of 1

Regulation Number and Section

§ 882.5275 Nerve cuff.

(a)
Identification. A nerve cuff is a tubular silicone rubber sheath used to encase a nerve for aid in repairing the nerve (e.g., to prevent ingrowth of scar tissue) and for capping the end of the nerve to prevent the formation of neuroma (tumors).(b)
Classification. Class II (performance standards).