The NervAlign® Nerve Cuff is indicated for the repair of peripheral nerve injuries in which there is no gap or where a gap closure is achieved by flexion of the extremity.

Device Description

The NervAlign® Nerve Cuff is a collagen membrane matrix derived from porcine pericardium. It is a sterile, whitish to light beige colored, freeze-dried, pre-cut, flat sheet of acellular collagen. The NervAlign® Nerve Cuff is available in three (3) different sizes: 10x10mm, 20x30mm and 30x40mm.

The collagen material that comprises the Nerve Cuff is derived from the same species as that of the predicate nerve cuff (AxoGuard Nerve Protector; K132660) manufactured by Cook Biotech Incorporated.

Like the predicate, the NervAlign® Nerve Cuff is implanted providing a scaffold which becomes infiltrated by the patient's cells and is remodelled into native tissue. The Nerve Cuff provides protection of the damaged nerve while the nerve heals.

The NervAlign® Nerve Cuff is packaged in a dried state, is for single use and provided sterile.

AI/ML Overview

This document is a 510(k) Premarket Notification from the FDA for a medical device called the "NervAlign Nerve Cuff." It focuses on demonstrating the substantial equivalence of the NervAlign Nerve Cuff to a legally marketed predicate device (AxoGuard Nerve Protector; K132660).

Based on the provided document, the device (NervAlign Nerve Cuff) is not an AI/ML powered device, nor does it involve human-in-the-loop performance, or a comparative effectiveness study with human readers (MRMC). Therefore, many of the requested criteria, such as "effect size of how much human readers improve with AI vs without AI assistance" or "Number of experts used to establish the ground truth for the test set and the qualifications of those experts", are not applicable to this specific device submission.

This submission relies on non-clinical performance testing to demonstrate substantial equivalence, rather than clinical studies involving human performance or diagnostic accuracy.

Here's the information that is applicable and can be extracted from the document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not present explicit "acceptance criteria" in a numerical or pass/fail table format with specific thresholds. Instead, the "Results" column from the "Performance Data" section effectively serves as the reported device performance and implicitly demonstrates that the device met the necessary standards for its intended use and for demonstrating substantial equivalence to the predicate.

Test	Test Method Summary	Reported Device Performance (Results)
Suture retention strength	A suture was placed through aged and unaged devices and the force required to pull free was measured.	Test was completed and met specification. Like predicate the device has sufficient strength for its intended use.
Thickness	Direct measurement of the device with micrometer when hydrated according to IFU.	Thickness measurements of device showed substantially equivalent to predicate.
Tensile Strength	Direct measurement of the device. Device placed between two grips and the separation force required to reach device failure was measured.	Test was completed and met specification. Like predicate device is suitable for intended use.
Cytotoxicity	The device was evaluated for potential cytotoxic effects using a mammalian cell line following ISO 10993-5 guidelines.	The test article extract showed no cytotoxic potential.
Sensitization	The device was evaluated for the potential to cause delayed dermal contact sensitization in guinea pigs based on ISO 10993-10.	Extracts of the test article showed no evidence of inducing delayed contact sensitization in the guinea pig.
Acute intracutaneous reactivity (Irritation)	The device was evaluated for the potential to cause irritation following intracutaneous injection in rabbits based on ISO 10993-10.	Extracts of the test article show no evidence of irritation.
Acute systemic toxicity	The device was evaluated for acute systemic toxicity in mice based on ISO 10993-11.	No mortality or evidence of systemic toxicity from both extracts, injected into mice.
Pyrogenicity	The device was evaluated for the potential to induce a pyrogenic response following intravenous injection in rabbits. Study conducted according to the United States Pharmacopeia (USP 41 - NF36, General Chapter <151>).	The test article met the requirements and is judged non-pyrogenic.
Hemolysis	The device was evaluated for hemolytic potential when in contact with blood based on ASTM F756 and requirements of ISO 10993-4.	The direct contact of the test article was slightly hemolytic. The extracts at 25, 12.5 and 6.25% were non-hemolytic. Device is suitable for intended indication. (Note: This result is presented as acceptable despite "slightly hemolytic" in direct contact, indicating agency's acceptance based on overall risk/benefit or context of use and non-hemolytic extracts).
Genotoxicity (AMES)	The device was evaluated for the potential to induce reverse mutations in Salmonella typhimurium and Escherichia coli tester strains per ISO 10993-3.	Extracts of the device were considered to be non-mutagenic to tester strains.
Genotoxicity (mouse lymphoma assay)	The device was evaluated to determine its mutagenic potential using the mouse lymphoma forward gene mutation assay per ISO 10993-3.	Test article considered non-mutagenic.
Endotoxin	Bacterial endotoxin testing is conducted per USP 85 and European Pharmacopoeia 2.6.14.	Device is produced and released with endotoxin level <2.15EU/device.
Subacute Systemic Toxicity & Local effects of Implantation	The device was surgically implanted in the subcutaneous tissue of rats for 4 weeks to evaluate its potential systemic toxicity and local tissue response.	The device showed no evidence of systemic toxicity. Device appeared as a well-integrated scaffold with remodelling responses. Microscopically the test article demonstrated minimal reaction to the tissue.
Sub-chronic Systemic Toxicity & Local effects of implantation	The device was surgically implanted in the subcutaneous tissue of rats for 8 and 13 weeks to evaluate potential systemic toxicity after 13 weeks and local tissue responses after 8 and 13 weeks.	On subcutaneous implantation the device showed no evidence of systemic toxicity after 13 weeks. Microscopically the test article demonstrated minimal tissue reaction compared to control. Device was bioresorbing at 13 weeks as expected.
6-Month Nerve Wrap Study in New-Zealand White Rabbits	The device was surgically implanted around the sciatic nerve of rabbits for 1, 2 & 6 months. The effects and compatibility of the wrapping material on the nerve and surrounding tissues were assessed.	The device was well tolerated with no device related clinical signs, changes in body weight, food consumption, neurological parameters, NCV, clinical pathology, or organ weights up to 6 months post-implantation. No adverse macroscopic or microscopic changes in the nerve and surrounding tissues were observed. No device related axonal degeneration was observed.
Rat transected sciatic nerve model	The device was surgically implanted around the transected sciatic nerve of the rat and compared to nerves wrapped with marketed predicate control material. Data were collected at 1, 4 and 13 weeks. Local tissue responses and device degradation were evaluated, and motor and sensory neurological assessments were conducted.	At all time points the changes observed in the nerve were similar between device and predicate control material and were typical of changes in a nerve after transection. At all time points the device was considered to elicit no or minimal reaction in comparison to the predicate control. The reactivity scores for device and predicate control decreased at later time points indicating healing. The device was markedly or completely degraded at 13 weeks, compared with the control device which was not degraded. Neuromas were not observed in any animal.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set: The document does not specify the exact numerical sample sizes (e.g., number of devices, number of animals) for each test. Instead, it describes the type of animal models used:
- Guinea pigs for Sensitization.
- Rabbits for Acute Intracutaneous Reactivity and Pyrogenicity.
- Mice for Acute Systemic Toxicity.
- Rats for Subacute Systemic Toxicity & Local effects of Implantation and Sub-chronic Systemic Toxicity & Local effects of Implantation.
- New-Zealand White Rabbits for 6-Month Nerve Wrap Study.
- Rats for Rat transected sciatic nerve model.
  The document focuses on the results rather than the specific numbers of subjects/samples per test.
Data Provenance: The document does not explicitly state the country of origin for the data generation. The company, ReNerve Ltd, is listed with an address in North Melbourne, Victoria, Australia. The studies are non-clinical (animal and lab-based physico-chemical) retrospective in nature, meaning they were conducted prior to this submission.

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

Not Applicable. This submission is based on non-clinical performance testing for substantial equivalence, not a diagnostic or prognostic performance study that would require human expert-established ground truth. The "ground truth" for these tests comes from established biological/chemical/physical assay standards (e.g., ISO 10993 guidelines, USP, ASTM).

4. Adjudication Method for the Test Set

Not Applicable. As per point 3, this is a non-clinical performance study, not a study where human readers would be assessing or adjudicating results.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size for human readers.

No, a MRMC comparative effectiveness study was not done. This is a non-AI, non-diagnostic medical device. The study evaluates the physical, chemical, and biological compatibility of the device itself.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done.

Not Applicable. This is not an algorithm or AI device.

7. The type of ground truth used.

For physical and chemical tests: Ground truth is established by the specified test methods and industry standards (e.g., ISO standards, USP, ASTM, internal specifications). For example, "Test was completed and met specification."
For biological compatibility (biocompatibility) and animal studies: Ground truth is established by the observed biological responses and histological findings in the tested animals, compared against established safety profiles and often against a control or predicate material (as seen in the rat sciatic nerve model comparing to predicate control material). The interpretation of these observations is made by trained personnel in the field (e.g., toxicologists, pathologists).

8. The sample size for the training set.

Not Applicable. This is not an AI/ML device that requires a training set. The "test set" in this context refers to the samples/animals used for the non-clinical performance testing.

9. How the ground truth for the training set was established.

Not Applicable. As per point 8, there is no "training set."

Summary

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February 10, 2022

Renerve Ltd % Chris Sloan President Sloan Regulatory Consulting LLC 322 Hart Road Gaithersburg, Maryland 20878

Re: K202234

Trade/Device Name: NervAlign Nerve Cuff Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: January 10, 2022 Received: January 11, 2022

Dear Chris Sloan:

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.

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

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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 mediation-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,

Adam D. Pierce, Ph.D. Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K202234

Device Name NervAlign® Nerve Cuff

Indications for Use (Describe)

The NervAlign® Nerve Cuff is indicated for the repair of peripheral nerve injuries in which there is no gap closure is achieved by flexion of the extremity.

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary NervAlign® Nerve Cuff K202234

Submitter

Name	ReNerve Ltd
Address	Suite 3, 21 Vale StreetNorth Melbourne, Victoria 3051Australia
Contact Person	David Rhodes
Phone	+61 (0)418598835
Email Address	drhodes@renerve.com.au
Date Prepared	February 2, 2022

Device

Trade Name	NervAlign® Nerve Cuff
Common Name	Nerve Cuff
Classification Name	Nerve Cuff
Classification Number	21 CFR 882.5275
Product Code	JXI
Regulatory Class	II

Predicate Device

Name [510(k) Number]	AxoGuard Nerve Protector [K132660]
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Device Description

The collagen material that comprises the Nerve Cuff is derived from the same species as that of the predicate nerve cuff (AxoGuard Nerve Protector; K132660) manufactured by Cook Biotech Incorporated.

The NervAlign® Nerve Cuff is packaged in a dried state, is for single use and provided sterile.

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Indications for Use

The NervAlign® Nerve Cuff is indicated for the repair of peripheral nerve injuries in which there is no gap or where a gap closure is achieved by flexion of the extremity.

Comparison of Technological Characteristics with the Predicate Device

The proposed device is substantially equivalent to the design and materials in the predicate device. The table below summarizes the comparison between the predicate device and the NervAlign® Nerve Cuff.

Feature	NervAlign® Nerve Cuff[Proposed Device]	AxoGuard Nerve Protector[Predicate Device]
510(k)	K202234	K132660
Device Class	Class II	Class II
Classification Name andNumber	Nerve Cuff; 21 CFR 882.5275	Nerve Cuff; 21 CFR 882.5275
Product Code	JXI	JXI
Indications for Use	The NervAlign® Nerve Cuff isindicated for the repair ofperipheral nerve injuries in whichthere is no gap or where a gapclosure is achieved by flexion of theextremity.	The Nerve Cuff is indicated forthe repair of peripheral nerveinjuries in which there is no gapor where a gap closure isachieved by flexion of theextremity. The device is providedsterile and intended for one-timeuse.
Principles of Operation	Collagen matrix intended to wrapand repair damaged peripheralnerves	Collagen matrix intended to wrapand repair damaged peripheralnerves
Material	Collagen Matrix - PorcinePericardium	Collagen Matrix – Porcine SmallIntestinal Submucosa (SIS)
Sterile/Single Use	Sterile; single use	Sterile; single use
Sterilization Method	Gamma Irradiation	Ethylene Oxide (EtO)

NervAlign® Nerve Cuff Comparison to AxoGuard Nerve Protector

Performance Data

The following testing was performed on the ReNerve NervAlign® Nerve Cuff.

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Test	Test Method Summary	Results
Suture retentionstrength	A suture was placed through aged andunaged devices and the force required topull free was measured.	Test was completed and met specification.Like predicate the device has sufficientstrength for its intended use.
Thickness	Direct measurement of the device withmicrometer when hydrated according toIFU.	Thickness measurements of device showedsubstantially equivalent to predicate.
Tensile Strength	Direct measurement of the device.Device placed between two grips and theseparation force required to reach devicefailure was measured.	Test was completed and met specification.Like predicate device is suitable forintended use.
Cytotoxicity	The device was evaluated for potentialcytotoxic effects using a mammalian cellline following ISO 10993-5 guidelines.	The test article extract showed no cytotoxicpotential.
Sensitization	The device was evaluated for thepotential to cause delayed dermalcontact sensitization in guinea pigsbased on ISO 10993-10.	Extracts of the test article showed noevidence of inducing delayed contactsensitization in the guinea pig.
Acute intracutaneousreactivity (Irritation)	The device was evaluated for thepotential to cause irritation followingintracutaneous injection in rabbits basedon ISO 10993-10.	Extracts of the test article show no evidenceof irritation.
Acute systemictoxicity	The device was evaluated for acutesystemic toxicity in mice based on ISO10993-11.	No mortality or evidence of systemictoxicity from both extracts, injected intomice.
Pyrogenicity	The device was evaluated for thepotential to induce a pyrogenic responsefollowing intravenous injection inrabbits. Study conducted according tothe United States Pharmacopeia (USP 41- NF36, General Chapter <151>).	The test article met the requirements and isjudged non-pyrogenic.
Hemolysis	The device was evaluated for hemolyticpotential when in contact with bloodbased on ASTM F756 and requirementsof ISO 10993-4.	The direct contact of the test article wasslightly hemolytic.The extracts at 25, 12.5 and 6.25% werenon-hemolytic.Device is suitable for intended indication.
Genotoxicity(AMES)	The device was evaluated for thepotential to induce reverse mutations inSalmonella typhimurium and	Extracts of the device were considered to benon-mutagenic to tester strains.
Test	Test Method Summary	Results
Escherichia coli tester strains per ISO10993-3.
Genotoxicity (mouselymphoma assay)	The device was evaluated to determineits mutagenic potential using the mouselymphoma forward gene mutation assayper ISO 10993-3.	Test article considered non-mutagenic.
Endotoxin	Bacterial endotoxin testing is conductedper USP 85 and EuropeanPharmacopoeia 2.6.14	Device is produced and released withendotoxin level <2.15EU/device.
Subacute SystemicToxicity & Localeffects ofImplantation	The device was surgically implanted inthe subcutaneous tissue of rats for 4weeks to evaluate its potential systemictoxicity and local tissue response.	The device showed no evidence of systemictoxicity. Device appeared as a well-integrated scaffold with remodellingresponses. Microscopically the test articledemonstrated minimal reaction to the tissue.
Sub-chronic SystemicToxicity & Localeffects ofimplantation	The device was surgically implanted inthe subcutaneous tissue of rats for 8 and13 weeks to evaluate potential systemictoxicity after 13 weeks and local tissueresponses after 8 and 13 weeks.	On subcutaneous implantation the deviceshowed no evidence of systemic toxicityafter 13 weeks.Microscopically the test articledemonstrated minimal tissue reactioncompared to control. Device wasbioresorbing at 13 weeks as expected.
6-Month Nerve WrapStudy in New-Zealand WhiteRabbits	The device was surgically implantedaround the sciatic nerve of rabbits for 1,2 & 6 months. The effects andcompatibility of the wrapping materialon the nerve and surrounding tissueswere assessed.	The device was well tolerated with nodevice related clinical signs, changes inbody weight, food consumption,neurological parameters, NCV, clinicalpathology, or organ weights up to 6 monthspost-implantation.No adverse macroscopic or microscopicchanges in the nerve and surroundingtissues were observed. No device relatedaxonal degeneration was observed.
Rat transected sciaticnerve model	The device was surgically implantedaround the transected sciatic nerve of therat and compared to nerves wrappedwith marketed predicate controlmaterial. Data were collected at 1, 4 and13 weeks.	At all time points the changes observed inthe nerve were similar between device andpredicate control material and were typicalof changes in a nerve after transection.At all time points the device was consideredto elicit no or minimal reaction incomparison to the predicate control
Test	Test Method Summary	Results
	Local tissue responses and devicedegradation were evaluated, and motorand sensory neurological assessmentswere conducted.	The reactivity scores for device andpredicate control decreased at later timepoints indicating healing.The device was markedly or completelydegraded at 13 weeks, compared with thecontrol device which was not degraded.Neuromas were not observed in any animal.

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Conclusions

The NervAlign® Nerve Cuff has the following similarities to the predicate device:

. Same intended use,
Same basic design,
Similar material, ●
Similar safety and performance characteristics, and ●
Same operating principles. ●

Based on the similarities of the intended use/indications for use, device design, principles of operation, technological characteristics and the results of the non-clinical performance testing, the subject device, NervAlign® Nerve Cuff, is substantially equivalent to the legally marketed predicate device.

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).