Reinforced Flexible Collagen Nerve Cuff

K170656 · Collagen Matrix, Inc. · JXI · Jun 1, 2017 · Neurology

Device Facts

• Record ID: K170656
• Device Name: Reinforced Flexible Collagen Nerve Cuff
• Applicant: Collagen Matrix, Inc.
• Product Code: JXI · Neurology
• Decision Date: Jun 1, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 882.5275
• Device Class: Class 2
• Attributes: Therapeutic

Indications for Use

Reinforced Flexible Collagen Nerve Cuff is used for the management of peripheral nerve injuries where gap closure can be achieved by flexion of the extremity (e.g., to prevent ingrowth of scar tissue).

Device Story

Resorbable, flexible type I collagen tubular matrix; circumferentially supported by resorbable synthetic polymer filament. Provides encasement for peripheral nerve injuries; protects neural environment; prevents scar tissue ingrowth. Synthetic filament enhances biomechanical stability and kink-resistance. Implanted at severed peripheral nerve gap; provides guidance for axonal growth. Used in clinical settings; operated by surgeons. Output is physical conduit; facilitates nerve regeneration. Benefits patient by supporting nerve repair.

Clinical Evidence

Bench testing and animal study provided. Bench testing: physical characterization (suture pullout, compression/kink resistance, permeability, hydrothermal transition) and biocompatibility (ISO 10993 series: cytotoxicity, sensitization, systemic toxicity, genotoxicity, pyrogenicity, implantation, haemocompatibility). Animal study: 48 rats with sciatic nerve excision; 16 subject device, 16 predicate, 16 autograft control. Sacrificed at 12 and 24 weeks. Evaluation via gross observation, histology, and histomorphometry showed robust nerve regeneration comparable to predicate and autograft.

Technological Characteristics

Type I bovine tendon collagen tubular matrix; resorbable synthetic polymer filament reinforcement. Dimensions: 2-6 mm ID, 2.5-3.0 cm length. Biocompatible; resorbable; crosslinked. Sterilization: ETO (SAL 10^-6). Non-pyrogenic (endotoxin ≤ 0.5 EU/ml). Mechanical properties: sutureable, compression-resistant, kink-resistant. Complies with ISO 10993-1, ISO 10993-3, ISO 10993-5, ISO 10993-6, ISO 10993-10, ISO 10993-11, and ASTM F756-13.

Indications for Use

Indicated for management of peripheral nerve injuries in discontinuities where gap closure can be achieved by flexion of the extremity.

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

• Flexible Collagen Nerve Cuff (K131541)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/2 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 image of three human profiles facing to the right, stacked on top of each other.

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

June 1 ,2017

Collagen Matrix, Inc. Peggy Hansen Senior Vice President 15 Thornton Road Oakland, New Jersey 07436

Re: K170656

Trade/Device Name: Reinforced Flexible Collagen Nerve Cuff Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: March 2, 2017 Received: March 3, 2017

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 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device

{1}------------------------------------------------

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 Industry and Consumer Education at its toll-free 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" (21 CFR 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 Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

# Michael J. Hoffmann -S

for

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

Enclosure

{2}------------------------------------------------

# Indications for Use

510(k) Number (if known) K170656

Device Name Reinforced Flexible Collagen Nerve Cuff

Indications for Use (Describe)

Reinforced Flexible Collagen Nerve Cuff is used for the management of peripheral nerve injuries where gap closure can be achieved by flexion of the extremity (e.g., to prevent ingrowth of scar tissue).

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

| Prescription Use (Part 21 CFR 801 Subpart D) | <div> </div> |
|----------------------------------------------|--------------|
| Over-The-Counter Use (21 CFR 801 Subpart C) | <div> </div> |

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff [e-mail]

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

### 510(k) SUMMARY

#### 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 |
| | SVP, Quality and Regulatory Affairs |
| Date Prepared: | April 28, 2017 |

#### 2. Name of the Device

| Device Common Name: | Nerve Cuff |
|------------------------------|-----------------------------------------|
| Device Trade Name: | Reinforced Flexible Collagen Nerve Cuff |
| Device Classification Name: | Nerve cuff |
| | 882.5275 |
| | JXI |
| | Class II |
| Device Classification Panel: | Neurology |
| | |

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

Predicate Device(s):

Flexible Collagen Nerve Cuff K131541

#### 4. Description of the Device

Reinforced Flexible Collagen Nerve Cuff is a resorbable, flexible type I collagen tubular matrix circumferentially supported with a resorbable synthetic polymer filament. The device provides both an encasement for peripheral nerve injuries as well as protection of the neural environment. The synthetic polymer filament provides enhanced support for biomechanical stability and kink-resistance of the collagen conduit. The Reinforced Flexible Collagen Nerve Cuff is an interface between the nerve and the surrounding tissue to prevent ingrowth of scar tissue. When implanted at a severed peripheral nerve gap, the Reinforced Flexible Collagen Nerve Cuff provides guidance for axonal growth across the gap. Upon hydration, the Reinforced Flexible Collagen Nerve Cuff is a soft, flexible collagen conduit with compression-resistant and kink-resistant properties. It is supplied sterile, nonpyrogenic, in various sizes and for single use only.

#### 5. Indications for Use

Reinforced 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).

{4}------------------------------------------------

#### 6. Summary/Comparison of Technical Characteristics

| Parameter | Reinforced Flexible Collagen Nerve<br>Cuff<br>(This submission) | Flexible Collagen Nerve Cuff<br>K131541 |
|------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for<br>Use | Intended for use in the management<br>of peripheral nerve injuries in<br>discontinuities where gap closure can<br>be achieved by flexion of the extremity<br>(e.g., to prevent ingrowth of scar<br>tissue). | Intended for use in the management of<br>peripheral nerve injuries in<br>discontinuities where gap closure can<br>be achieved by flexion of the extremity<br>(e.g., to prevent ingrowth of scar<br>tissue) or at the end of the nerve in the<br>foot to prevent the formation of<br>symptomatic or painful neuroma. |
| Material | Type I collagen with absorbable<br>polymeric suture filament | Type I collagen |
| Source of<br>collagen | Bovine tendon | Bovine tendon |
| Form | Tubular matrix | Tubular matrix |
| Color | White to off-white | White to off-white |
| 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<br>Addition of a 3.0 cm length size for all<br>diameters. | 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 |
| Mechanical<br>Strength | Can be sutured | Can be sutured |
| pH | 6 - 9 | 6 - 9 |
| Resorbable | Yes | Yes |
| Crosslinked | Yes | Yes |
| Biocompatibility | Biocompatible | Biocompatible |
| Sterility | Sterile, SAL 10-6<br>ETO sterilization | Sterile, SAL 10-6<br>Gamma irradiation |
| Pyrogenicity | Non-pyrogenic<br>Endotoxin ≤ 0.5 EU/ml | Non-pyrogenic<br>Endotoxin ≤ 0.5 EU/ml |
| Single<br>Use/Reuse | Single use only | Single use only |
| Packaging | Double peel package | Double peel package |

#### Nonclinical Tests Submitted

The substantial equivalence of the Reinforced Flexible Collagen Nerve Cuff to its predicate device was demonstrated based on an evaluation of the product safety, product characteristics, and performance in an animal model.

In vitro characterization studies included evaluation of physical properties such as suture pullout strength, compression resistance, kink resistance, and an evaluation of physicochemical properties such as product permeability and hydrothermal

{5}------------------------------------------------

transition temperature. The characterization test results of the subject device were equivalent to those of the predicate device.

The Reinforced Flexible Collagen Nerve Cuff subject device was evaluated in a number of in vitro and in vivo tests to assess its safety/biocompatibility. The subject device passed all applicable tests in accordance with ISO 10993-1 and FDA Guidance on Use of International Standard ISO 10993-1 for the biological evaluation of medical devices within a risk management process.

| Test | Test Method/Model | Results |
|-----------------------------------|---------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Physical<br>Characterization | Suture pullout,<br>compression resistance,<br>kink resistance,<br>permeability,<br>hydrothermal transition<br>temperature | Test results of the finished subject device are<br>comparable to the predicate device. |
| Animal<br>Performance | Rat sciatic nerve study | Test results of the finished subject device are<br>comparable to the predicate device. |
| Cytotoxicity | Agarose Overlay, ISO<br>10993-5 | Non-cytotoxic; No evidence of causing any<br>cell lysis or toxicity. |
| | MEM Elution Using L-<br>929 Mouse Fibroblast<br>Cells, ISO 10993-5 | The test article scored '0' at 24, 48, and 72 ± 4<br>hours and is considered non-cytotoxic under<br>the conditions of the test. |
| Sensitization | Guinea Pig<br>Maximization, ISO<br>10993-10 | No evidence of causing delayed dermal<br>contact sensitization in the guinea pig. The<br>test article was not considered a sensitizer in<br>the guinea pig test. |
| Intracutaneous<br>Reactivity | Intracutaneous Study in<br>Rabbits, ISO 10993-10 | Under the conditions of the study, there was<br>no irritation or toxicity from the extract injected<br>intracutaneously into rabbits. |
| Acute Systemic<br>Toxicity | Acute Systemic Toxicity<br>in Mice, ISO 10993-11 | No mortality or evidence of systemic toxicity<br>up to 72 hours. |
| Subchronic<br>(Systemic) Toxicity | Systemic Toxicity in<br>Rabbits, ISO 10993-11 | No evidence of systemic toxicity or adverse<br>findings specifically attributed to the test article<br>up to 13 weeks. |
| Genotoxicity | Bacterial Reverse<br>Mutation Study, ISO<br>10993-3 | Non-mutagenic to Salmonella typhimurium<br>(strains TA97a, TA98, TA100, TA1535) and to<br>Escherichia coli (strain WP2-uvra) |
| | Mouse Lymphoma<br>Assay, ISO 10993-3 | Based on the criteria and conditions of the<br>study protocol, the test article is considered<br>non-mutagenic (non-genotoxic and non-<br>clastogenic) |
| Test | Test Method/Model | Results |
| Material-Mediated<br>Pyrogenicity | Rabbit Pyrogen study-<br>USP <151> | Non-pyrogenic. None of the rabbits<br>administered with the test article extract had a<br>temperature rise ≥0.5°C at the observation<br>time points. |
| Implantation | Local Tissue Reaction in<br>a Subcutaneous Implant<br>in Rabbits, ISO 10993-6 | The test article result was considered<br>acceptable at 2 weeks and 13 weeks when<br>compared to the control article. |
| Haemocompatibility | Hemolysis Assay –<br>Extract Method, ASTM<br>F756-13 | The test article was considered non-hemolytic<br>under the test conditions employed. |
| Chronic Toxicity<br>Degradation | Local Tissue Reaction<br>and Resorption in a<br>Subcutaneous Implant<br>in Rabbits, ISO 10993-6 | The test article result was considered<br>acceptable at 26 weeks when compared to the<br>control article. Resorption of test article and<br>incorporation into new host collagen was<br>advanced at 26 weeks. |

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

{6}------------------------------------------------

## Animal Study

In the animal study conducted, 48 rats underwent excision of a segment of the sciatic nerve. In 16 of 48 rats, the nerve injuries were treated with the subject device, in another 16 rats the nerve injuries were treated with the predicate device, and in the remaining 16 rats, the nerve injuries were treated with an autograft control. There were no procedure related complications or premature deaths in the study.

Animals were sacrificed at 12 weeks and 24 weeks. The nerve repair segments were evaluated by gross observation, histological, and histomorphometrical methods. The study demonstrated that nerve regeneration was robust for both the subject and predicate devices.

#### Conclusions Drawn from Non-clinical Studies

Subject and predicate device performance data were compared to support the safety of the subject device and demonstrate that the Reinforced Flexible Collagen Nerve Cuff should perform as intended in the specified use conditions.