NeuroGen" Nerve Guide is an implant designed for repair of peripheral nerve discontinuities. NeuroGen™ Nerve Guide provides a protective environment for peripheral nerve repair after injury. NeuroGen" Nerve Guide is designed to be an interface between the nerve and surrounding tissue and to create a conduit for axonal growth across a nerve gap.

NeuroGen" Nerve Guide is flexible to accommodate movement of joint and associated tendons while retaining its shape and is resistant to occlusive forces from surrounding tissue. When hydrated, NeuroGen" is an easy to handle, soft, pliable, nonfriable, porous collagen tube. NeuroGen™ Nerve Guides are provided sterile in double blister packages in a variety of sizes.

AI/ML Overview

The NeuroGen™ Nerve Guide is a device for repairing peripheral nerve discontinuities. The provided documents focus on its substantial equivalence to predicate devices based on safety and performance in animal studies, rather than defining specific statistical acceptance criteria for its effectiveness in humans. Therefore, it's not possible to generate a table of acceptance criteria and reported device performance in the typical sense of a human clinical trial with defined metrics like sensitivity or specificity.

However, based on the provided text, we can describe the studies conducted to demonstrate its safety and performance:

1. Table of Acceptance Criteria and Reported Device Performance

As specific statistical acceptance criteria for human device performance (e.g., success rate of nerve repair) and corresponding reported performance are not present in this 510(k) summary, this section will describe the types of criteria the device aimed to meet through its testing and the general outcomes reported.

Acceptance Criterion Type (Implied)	Reported Device Performance
Biocompatibility	- Noncytotoxic - Nonpyrogenic - Nonirritating - Nonsensitizing - Acute Systemic Toxicity (no toxicity) - Subchronic Toxicity (no toxicity) - Chronic Toxicity (no toxicity) - Genotoxicity (non-mutagenic) - Implantation (biocompatible) - Hemolysis (no hemolysis)
Effectiveness in Nerve Repair	Demonstrated to be substantially equivalent to nerve graft, direct suture, and silicone tubes for repairing peripheral nerve discontinuities in animal models. The studies confirmed it provides a protective environment for peripheral nerve repair and creates a conduit for axonal growth. Long-term evaluations in primates demonstrated it is biocompatible and provides an environment for axonal growth.
Mechanical Properties	- Suture retention: Able to hold a suture. - Mechanical compression: Resistant to repeated compression from surrounding tissues.
Physical Properties	- Porosity: Porous outer surface and tube wall. - Permeability: Allows the passage of molecules of specific size through the tube wall. - Flexibility: Flexible to accommodate movement of joint and associated tendons. - Shape Retention: Retains its shape despite movement. - Resistance to Occlusive Forces: Resistant to occlusive forces from surrounding tissue. - Handling: When hydrated, easy to handle, soft, pliable, nonfriable.
Substantial Equivalence	NeuroGen™ Nerve Guide is substantially equivalent in function and intended use to Salumedica™ Nerve Cuff, NeuroTube®, and Fastube™ Nerve Cuff. It is a tubular device, provided sterile, for single use, and manufactured from a bioresorbable material (like NeuroTube®).

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

Sample Size:
- Animal Studies: Not explicitly stated for specific numbers of animals, but refers to "a long-term (3.5 years) primate study and in rodent animal models."
- Biocompatibility/Mechanical/Physical Tests: Not specified in terms of sample size (e.g., number of guides tested), but mentions "a series of tests."
Data Provenance: Not specified (e.g., country of origin). The studies appear to be pre-clinical animal and laboratory tests rather than human clinical data. They are retrospective or prospective in the sense of being conducted as part of the device's development and regulatory submission.

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

This information is not provided. The ground truth for effectiveness was established in animal models, likely through histological analysis, functional recovery assessment, and comparison to established nerve repair methods. The ground truth for biocompatibility, mechanical, and physical properties was established through standardized laboratory testing.

4. Adjudication Method for the Test Set

This information is not provided, as the studies are primarily animal and laboratory-based. Adjudication methods are typically relevant for human clinical trials or expert-based assessments of medical imaging.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No MRMC comparative effectiveness study was done. This device is a physical implant, not an AI-assisted diagnostic or interpretative tool.

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

Not applicable. This device is a physical implant, not an algorithm.

7. The Type of Ground Truth Used

Effectiveness (Nerve Repair):
- Animal model outcomes (e.g., histological evidence of axonal growth, functional recovery, comparison to established repair methods like nerve graft, direct suture, and silicone tubes).
Biocompatibility: In vitro and in vivo toxicological assessments (e.g., cell viability, pyrogenicity tests, irritation assays, systemic toxicity endpoints, implantation site reactions).
Mechanical and Physical Properties: Laboratory measurements using established test methods for suture retention, compression resistance, porosity, and permeability.

8. The Sample Size for the Training Set

Not applicable. This is a physical medical device, not an AI algorithm that requires a training set.

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

Not applicable.

Summary

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NeuroGen™ Nerve Guide

JUN 2 2 2001

510(K) SUMMARY

Submitter's name and address:

Integra LifeSciences Corporation 105 Morgan Lane Plainsboro, NJ 08536 USA

Contact person and telephone number:

Judith E. O'Grady Senior Vice President, Regulatory Affairs, Quality Assurance and Clinical Research (609) 275-0500

Date Summary was prepared:

April 16, 2001

Name of the device:

Proprietary Name:	NeuroGen™
Common Name:	Nerve Guide
Classification Name:	Nerve Cuff, Product Code 84JXI

Substantial Equivalence:

NeuroGen™ Nerve Guide is substantially equivalent in function and intended use to the following products which have been cleared to market under Premarket Notifications 510(k): Salumedica" Nerve Cuff, NeuroTube and Fastube" Nerve Cuff.

Device Description:

Intended Use:

NeuroGen" Nerve Guide is indicated for repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.

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Safety

Biocompatibility studies have demonstrated NeuroGen™ Nerve Guides to be: noncytotoxic, nonpyrogenic, nonirritating, and nonsensitizing. The following studies were conducted:

a) Cytotoxicity
b) Irritation / Intracutaneous Reactivity
Sensitization c)
d) Acute Systemic Toxicity
e) Subchronic Toxicity
Chronic Toxicity f)
Genotoxicity g)
h) Implantation
Hemolysis i)

Performance Characteristics:

The effectiveness of NeuroGen™ Nerve Guide to repair peripheral nerve discontinuities was studied in a long-term (3.5 years) primate study and in rodent animal models. The studies demonstrated that NeuroGen™ Nerve Guides are substantially equivalent to nerve graft, direct suture and silicone tubes.

The mechanical and physical characteristics of the NeuroGen™ Nerve Guides were evaluated in a series of tests. These tests were conducted to ensure that the NeuroGen™ Nerve Guides possess the mechanical properties (suture retention and mechanical compression) as well as physical properties (porosity and permeability) that determine their suitability for use in the human body. Testing has demonstrated that the nerve guides are able to hold a suture, resist repeated compression from surrounding tissues, have a porous outer surface and tube wall, and allow the passage of molecules of specific size through the tube wall.

Technological Characteristics Compared to Predicate Devices:

NeuroGen™ Nerve Guide is a tubular device which is equivalent to the predicate devices, Salumedica™ Nerve Cuff. NeuroTube® and Fastube™ Nerve Cuff in its design for repair of peripheral nerve discontinuities. Like the predicate devices, NeuroGen" is provided sterile, for single use only. The NeuroGen™ Nerve Guide is manufactured from a bioresorbable material, as is one of the predicate devices, NeuroTube®. NeuroGen™ Nerve Guide meets ISO 10993 requirements for Biocompatibility testing.

Conclusion

NeuroGen" Nerve Guide is indicated for the repair of nerve discontinuities where gap closure can be achieved by flexion of the extremity. NeuroGen™ Nerve Guide is flexible to accommodate movement of joint and associated tendons while retaining its shape and is resistant to occlusive forces from surrounding tissue.

Biocompatibility studies have demonstrated NeuroGen" Nerve Guide to be non-cytotoxic, nonsensitizing, non-toxic and non-mutagenic. Extensive, long-term evaluations in primates demonstrates NeuroGen™ Nerve Guide to biocompatible and provides an environment for axonal growth.

Valid scientific evidence through substantial testing of descriptive characteristics, Biocompatibility, mechanical and physical property testing and extensive performance testing in a primate model, provide reasonable assurance that NeuroGen™ Nerve Guide is safe and effective under the proposed conditions of use, and substantially equivalent to its predicate devices.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles three overlapping human profiles or a bird in flight, composed of curved lines.

Public Health Service

JUN 2 2 2001

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Ms. Judith E. O'Grady, RN, MSN Senior Vice President, Regulatory Affairs, Quality Assurance and Clinical Affairs Integra Life Sciences Corporation 105 Morgan Lane Plainsboro, New Jersey 08536

Re: K011168

Trade/Device Name: NeuroGen Nerve Guide Regulation Number: 882.5275 Regulatory Class: II Product Code: JXI Dated: April 16, 2001 Received: April 17, 2001

Dear Ms. O'Grady:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2 - Ms. Judith E. O'Grady, RN, MSN

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4659. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours.

Marlen Millenor

Celia M. Witten, Ph.D., M.D. Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number:

K011168

Device Name: NeuroGen™ Nerve Guide

Indications for Use

NeuroGen™ Nerve Guide is indicated for repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.

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

(Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use OR Over-the-Counter Use X (Per 21 CFR 801.109)

Mark N. Milhusan

(Division Sign-Off) (Division of General, Restorative and Neurological Devices

510(k) Number -

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).