FLEXIBLE COOAGEN NERVE CUFF

K131541 · Collagen Matrix, Inc. · JXI · Apr 3, 2014 · Neurology

Device Facts

• Record ID: K131541
• Device Name: FLEXIBLE COOAGEN NERVE CUFF
• Applicant: Collagen Matrix, Inc.
• Product Code: JXI · Neurology
• Decision Date: Apr 3, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 882.5275
• Device Class: Class 2
• Attributes: Therapeutic, Real-World Evidence

Real-World Evidence

Submission	Device	Sponsor	RWD Sources	RWE Use Summary	Key Tags
K131541 · Apr 3, 2014	FLEXIBLE COOAGEN NERVE CUFF	Collagen Matrix, Inc.	Clinical study of patients undergoing routine surgical excision and device implantation; Clinical literature review and meta-analysis of published studies	The sponsor provided a clinical study of 50 patients to evaluate pain reduction following the use of the Flexible Collagen Nerve Cuff for foot neuromas. A literature review and meta-analysis were used to compare these results against the Silastic Nerve Cuff predicate and excision-only control groups to support substantial equivalence for the expanded indication.	Neuroma; Foot surgery; Pain reduction; Clinical literature review; Meta-analysis

Clinical Evidence

Study Design	Population	Comparator	Key Endpoints
Clinical study of Flexible Collagen Nerve Cuff for painful neuromas of the foot; Retrospective clinical cohort study; Follow-up/Duration: Mean follow-up 36 months (range 6-55 months)	Patients with painful single or multiple neuromas of the foot; Sample Size: 50 patients (60 nerves)	Not applicable for this study	Reduction of pain (1-10 scale)
Clinical literature review and meta-analysis; Literature review and meta-analysis	Patients treated for nerve ends of the foot	Silastic Nerve Cuff and nerve excision alone	Post-operative pain reduction

Indications for Use

Flexible Collagen Nerve Cuff is used for the management of peripheral nerve injuries in discontinuities where gap closure can be achieved by flexion of the extremity (e.g., to prevent ingrowth of scar tissue) or at the end of the nerve in the foot to reduce the formation of symptomatic or painful neuroma.

Device Story

Flexible Collagen Nerve Cuff is a resorbable, flexible type I collagen tubular matrix; provides encasement for peripheral nerve injuries; protects neural environment; acts as interface between nerve and surrounding tissue to prevent scar tissue ingrowth. When placed at terminal nerve ends, prevents neuroma formation. Features crimped walls for kink-resistance. Supplied sterile, non-pyrogenic, single-use. Used by clinicians in surgical settings. Device provides physical barrier; output is the physical protection of the nerve site. Benefits include reduced scar tissue ingrowth and reduced formation of symptomatic or painful neuromas.

Clinical Evidence

Clinical study of 50 patients (ages 16-77, mean 54) undergoing excision of painful neuromas in the foot. 60 nerves treated with Flexible Collagen Nerve Cuff. Mean follow-up 36 months. Primary endpoint: pain reduction (1-10 scale). Results: 93% success rate in reducing pain. Meta-analysis compared subject device to Silastic Nerve Cuff and excision-only control; subject device performed substantially equivalent to predicate and showed clinically significant improvement over excision-only.

Technological Characteristics

Resorbable, flexible type I collagen tubular matrix derived from bovine tendon. Semi-permeable to nutrients and macromolecules. Features crimped walls for kink-resistance. Can be sutured. Sterilized via gamma irradiation (SAL 10-6). Non-pyrogenic (endotoxin ≤ 0.5 EU/ml). Biocompatible per ISO 10993-1 and FDA Blue Book G95-1.

Indications for Use

Indicated for management of peripheral nerve injuries in discontinuities where gap closure is achievable via extremity flexion, or for capping nerve ends in the foot to reduce symptomatic/painful neuroma formation.

Regulatory Classification

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).

Predicate Devices

• Collagen Nerve Cuff (K012814)
• Silastic® Nerve Cuff

Submission Summary (Full Text)

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# 510(k) SUMMARY

K131541

# 1. Applicant Information

| Applicant Name: | Collagen Matrix, Inc. |
|-----------------|---------------------------------------------|
| Address: | 15 Thornton Road |
| | Oakland, New Jersey 07436 |
| Telephone: | [phone] |
| Fax: | [phone] |
| Contact Person: | Peggy Hansen, RAC |
| | VP, Clinical, Regulatory, QA, and Marketing |
| Date Prepared: | March 31, 2014 |

# 2. Name of the Device

Device Common Name: Device Trade Name: Device Classification Name: Nerve Cuff Flexible Collagen Nerve Cuff Nerve cuff 882.5275 JXI · Class II

#### 3. Legally Marketed Devices to Which Substantial Equivalence is Claimed

Predicate Device(s):

Collagen Nerve Cuff K012814

Silastic® Nerve Cuff Pre-amendment Device

#### Description of the Device 4.

Flexible Collagen Nerve Cuff is a resorbable, flexible type I collagen tubular matrix that provides both an encasement for peripheral nerve injuries as well as protection of the neural environment. Flexible Collagen Nerve Cuff is designed to be an interface between the nerve and the surrounding tissue (e.g., to prevent ingrowth of scar tissue). When placed at the terminal end of a nerve, the Flexible Collagen Nerve Cuff is designed to prevent formation of neuroma. When hydrated, Flexible Collagen Nerve Cuff is a flexible collagen conduit where the crimped walls provide a kink-resistant property to the tube. It is supplied sterile, non-pyrogenic, in various sizes and for single use only.

# 5. Indications for Use / Intended Use

Flexible Collagen Nerve Cuff is used for the management of peripheral nerve injuries in discontinuities where gap closure can be achieved by flexion of the extremity (e.g., to prevent ingrowth of scar tissue) or at the end of the nerve in the foot to reduce the formation of symptomatic or painful neuroma.

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# 6. Summary/Comparison of Technical Characteristics

Flexible Collagen Nerve Cuff is the identical product to the Company's currently marketed Neuroflex™ Collagen Nerve Cuff. The 510(k) premarket notification was submitted for expanded indications.

| Parameter | Flexible Collagen Nerve<br>Cuff<br>(This submission) | Collagen Nerve Cuff<br>K012814 | Silastic® Nerve Cuff |
|---------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | Intended for use in the<br>management of<br>peripheral nerve injuries<br>in discontinuities where<br>gap closure can be<br>achieved by flexion of<br>the extremity (e.g., to<br>prevent ingrowth of scar<br>tissue) or at the end of<br>the nerve in the foot to<br>reduce the formation of<br>symptomatic or painful<br>neuroma. | Intended for use in the<br>repair of peripheral nerve<br>discontinuities where gap<br>closure can be achieved<br>by flexion of the<br>extremity. | Intended to be used to<br>encase a nerve for aid in<br>repairing the nerve (e.g., to<br>prevent ingrowth of scar<br>tissue) and for capping the<br>end of the nerve to prevent<br>the formation of neuroma<br>(tumors). |
| Material | Type I collagen | Type I collagen | Silicone |
| Source | Bovine tendon | Bovine tendon | Synthetic |
| Form | Tubular matrix | Tubular matrix | Tubular matrix |
| Color | White to off-white | White to off-white | Opaque |
| Sizes | 2 mm ID x 2.5 cm length<br>2.5 mm ID x 2.5 cm length<br>3 mm ID x 2.5 cm length<br>4 mm ID x 2.5 cm length<br>5 mm ID x 2.5 cm length<br>6 mm ID x 2.5 cm length | 2 mm ID x 2.5 cm length<br>2.5 mm ID x 2.5 cm length<br>3 mm ID x 2.5 cm length<br>4 mm ID x 2.5 cm length<br>5 mm ID x 2.5 cm length<br>6 mm ID x 2.5 cm length | 3.3 mm ID x 1.0 cm length<br>4.1 mm ID x 1.0 cm length<br>4.8 mm ID x 1.0 cm length<br>5.3 mm ID x 1.3 cm length<br>6.1 mm ID x 1.3 cm length<br>7.1 mm ID x 1.3 cm length<br>7.9 mm ID x 1.5 cm length<br>8.6 mm ID x 1.5 cm length<br>9.9 mm ID x 1.5 cm length<br>10.7 mm ID x 1.5 cm length<br>11.7 mm ID x 1.8 cm length<br>13.7 mm ID x 1.8 cm length |
| Mechanical<br>Strength | Can be sutured | Can be sutured | Can be sutured |
| Resorbable | Yes | Yes | No |
| Crosslinked | Yes | Yes | No |
| Porosity/<br>Permeability | Semi-permeable.<br>Permeable to nutrients<br>and macromolecules | Semi-permeable<br>Permeable to nutrients<br>and macromolecules | Non-permeable |
| Biocompatibility | Biocompatible | Biocompatible | Biocompatible |
| Sterility | Sterile, SAL 10-6<br>Gamma irradiation | Sterile, SAL 10-6<br>Gamma irradiation | Sterile |
| Pyrogenicity | Non-pyrogenic<br>Endotoxin ≤ 0.5 EU/ml | Non-pyrogenic<br>Endotoxin ≤ 0.5 EU/ml | Unknown |
| Single Use/Reuse | Single use only | Single use only | Single use only |
| Parameter | Flexible Collagen Nerve<br>Cuff<br>(This submission) | Collagen Nerve Cuff<br>K012814 | Silastic® Nerve Cuff |
| Packaging | Double peel package | Double peel package | Sterile vials of distilled<br>water |

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# Nonclinical Tests Submitted

The substantial equivalence of the Flexible Collagen Nerve Cuff and its predicate device was demonstrated based on an evaluation of the expanded indications.

In vitro characterization studies included evaluation of physical properties such as suture strength, kink resistance, and an evaluation of physicochemical properties such as product permeability and hydrothermal transition temperature. The characterization test results of the subject device were equivalent to those of the predicate device, given that there has been no change to the device itself.

The Flexible Collagen Nerve Cuff material was evaluated in a number of in vitro and in vivo tests to assess its safety/biocompatibility. The representative product passed all applicable FDA Blue Book Memorandum G95-1and ISO 10993-1 testing for the biological evaluation of medical devices.

| Test | Results | Conclusions |
|----------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|
| Cytotoxicity -<br>Agarose<br>Overlay | No evidence of causing any cell lysis or toxicity. | Non-cytotoxic |
| Sensitization -<br>Guinea Pig<br>Maximization | No evidence of causing delayed dermal contact<br>sensitization in the guinea pig. The test article<br>was not considered a sensitizer in the guinea<br>pig test. | Non-sensitizer |
| Intracutaneous<br>Reactivity | Under the conditions of the study, there was no<br>irritation or toxicity from the extract injected<br>intracutaneously into rabbits. | Non-irritant, non-toxic |
| Acute Systemic<br>Toxicity | No mortality or evidence of systemic toxicity | Non-toxic<br>(acute systemic) |
| Genotoxicity -<br>Bacterial<br>Reverse<br>Mutation | Non-mutagenic to Salmonella typhimurium and<br>to Escherichia coli strain WP2uvra | Non-mutagenic |
| Mouse<br>Lymphoma<br>Assay | None of the test article treatments induced<br>substantial increases in the number of revertant<br>colonies. | Non-mutagenic |
| In Vivo Mouse<br>Micronucleus<br>Assay | None of the mice treated with the test article<br>preparations exhibited overt signs of toxicity<br>either immediately post-treatment or during the<br>induction period. The levels of micronucleated<br>cells were within normal negative ranges. | Non-mutagenic |

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Collagen Matrix, Inc. 510(k) Summary Flexible Collagen Nerve Cuff Page 4 of 4

| Test | Results | Conclusions |
|----------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------|
| Pyrogenicity -<br>Rabbit Pyrogen | Non-pyrogenic | Non-pyrogenic |
| Muscle<br>Implantation | The macroscopic reaction was not significant<br>compared with the USP negative control<br>implant material. Microscopically, the test<br>article was classified as a nonirritant as<br>compared to the USP negative control article. | Non-irritant |
| Subacute/<br>Subchronic/<br>Chronic Toxicity | Minimum tissue reaction up to 24 weeks of<br>implantation and no adverse tissue reaction to<br>the host. | Non toxic<br>(subacute, subchronic,<br>chronic) |

Viral inactivation studies were performed to ensure the viral safety of the product.

# Clinical Test Submitted

A clinical study was submitted that evaluated the use of the Flexible Collagen Nerve Cuff in the management of painful neuromas of the foot. A total of 50 patients underwent excision of painful single or multiple neuromas with the end of the resected nerve sutured into the Flexible Collagen Nerve Cuff subject device. Each patient preoperatively was asked to describe the amount of pain he or she was experiencing on a scale from 1 to 10, with 10 indicating the most severe pain. In the telephone interview conducted during this study, the same question was asked of each patient following revision. Patient ages ranged from 16 to 77 years, with a mean of 54 years. In all, 30 right and 20 left sides were operated, and 1 patient had bilateral involvement. Mean follow-up was 36 months (6-55 months). There were a total of 60 nerves that underwent conduit procedures in the foot. The results showed a 93% success rate of reducing pain for the treatment of neuroma in the foot.

A clinical literature review and meta-analysis was further conducted to compare the results of the clinical study of the Flexible Collagen Nerve Cuff subject device with published studies of the Silastic Nerve Cuff predicate device and nerve excision alone, specifically for treatment of nerve ends of the foot. The analysis showed that the Flexible Collagen Nerve Cuff performs substantially equivalent to its predicate device (Silastic Nerve Cuff) with respect to reduction of pain post-operatively. In addition, both devices show clinically significant improvement in pain reduction over the excision-only control group.

#### Conclusions Drawn from Non-clinical and Clinical Studies

The results of the material evaluation, in vitro product characterization studies, biocompatibility studies, animal and clinical studies show that the Flexible Collagen Nerve Cuff is safe and substantially equivalent to the predicate device. The expanded indication for use does not affect the safety and performance of the device.

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# DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

April 3, 2014

Collagen Matrix, Inc. Ms. Peggy Hansen, Vice President Clinical Regulatory, QA & Marketing 15 Thornton Road Oakland, NJ 07436

Re: K131541 .

Trade/Device Name: Neuroflex TM Collagen Nerve Cuff Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: March 6, 2014 Received: March 7, 2014

Dear Ms. Hansen:

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. 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 notc: 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 requirements, including, but not limited to: registration and listing (21

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# Page 2 - Ms. Peggy Hansen

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 contact the Division of Small Manufacturers. International and Consumer Assistance at its tollfree number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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/ReportaProblem/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 [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Joyce M. Whang -S

fox Carlos L. Peña, PhD, MS Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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#### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

# Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.

# 510(k) Number (if known) K131541

#### Device Name Flexible Collagen Nerve Cuff

# Indications for Use (Describe)

Flexible Collagen Nerve Cuff is used for the management of peripheral nerve injuries in discontinuities where gap be achieved by flexion of the extremity (e.g., to prevent ingrowth of scar tissue) or at the nerve in the foot to reduce the formation of symptomatic or painful neuroma.

Type of Use (Select one or both, as applicable)

[ Prescription Use (Part 21 CFR 801 Subpart D)

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

# PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

### FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signalure)

**Joyce M. Whang -S**

FORM FDA 3881 (1/14)

PSC Publishing Services (30) ) 443-6740 FF

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