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 Description

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.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device called "Reinforced Flexible Collagen Nerve Cuff." It focuses on demonstrating substantial equivalence to a predicate device rather than presenting a study proving that the device meets specific acceptance criteria in the way an AI/ML device would.

Therefore, many of the requested sections related to acceptance criteria, MRMC studies, standalone performance, and ground truth establishment for AI/ML models cannot be extracted or inferred from this document. This document details the regulatory approval process for a biomedical device based on non-clinical and animal studies, not an AI/ML algorithm.

However, I can extract information related to the device's performance based on the comparison to the predicate device in the provided non-clinical and animal studies.

Here's the information that can be extracted, and an explanation of why other requested information is not applicable:

1. Table of Acceptance Criteria and Reported Device Performance

This document does not specify "acceptance criteria" in terms of precise numerical thresholds for clinical performance (e.g., sensitivity, specificity) as would be the case for an AI/ML medical device. Instead, the "acceptance" is based on demonstrating substantial equivalence to a legally marketed predicate device through various non-clinical and animal studies, showing comparable safety and performance characteristics.

The "performance" is reported as being "comparable" to the predicate device or passing standard biological tests.

Parameter/Test	Acceptance Criteria (Inferred from Substantial Equivalence Goal)	Reported Device Performance
Physical Characterization	Must be comparable to predicate device.	Test results of the finished subject device are comparable to the predicate device for suture pullout, compression resistance, kink resistance, permeability, and hydrothermal transition temperature.
Animal Performance	Must demonstrate robust nerve regeneration comparable to predicate device and autograft.	Nerve regeneration was robust for both the subject and predicate devices.
Cytotoxicity	Non-cytotoxic (no cell lysis or toxicity).	Non-cytotoxic; No evidence of causing any cell lysis or toxicity. Test article scored '0' (non-cytotoxic).
Sensitization	No evidence of delayed dermal contact sensitization.	No evidence of causing delayed dermal contact sensitization in the guinea pig. Test article not considered a sensitizer.
Intracutaneous Reactivity	No irritation or toxicity.	No irritation or toxicity from the extract injected intracutaneously.
Acute Systemic Toxicity	No mortality or evidence of systemic toxicity.	No mortality or evidence of systemic toxicity up to 72 hours.
Subchronic Toxicity	No evidence of systemic toxicity or adverse findings.	No evidence of systemic toxicity or adverse findings specifically attributed to the test article up to 13 weeks.
Genotoxicity	Non-mutagenic/non-genotoxic.	Non-mutagenic to tested bacterial strains. Considered non-mutagenic (non-genotoxic and non-clastogenic).
Material-Mediated Pyrogenicity	Non-pyrogenic (temperature rise < 0.5°C).	Non-pyrogenic. None of the rabbits had a temperature rise ≥0.5°C.
Implantation (Local Tissue Reaction)	Acceptable local tissue reaction compared to control.	The test article result was considered acceptable at 2 weeks and 13 weeks compared to the control article.
Haemocompatibility	Non-hemolytic.	The test article was considered non-hemolytic.
Chronic Toxicity/Degradation	Acceptable local tissue reaction and resorption compared to control.	The test article result was considered acceptable at 26 weeks compared to the control article. Resorption and incorporation into new host collagen advanced at 26 weeks.
Viral Inactivation	Viral safety ensured.	Viral inactivation studies were performed to ensure the viral safety of the product.

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

Test Set Description: The "test set" in this context refers to the animals studied in the performance and toxicology tests. It's not a clinical data set for AI/ML.
Sample Size:
- Animal Performance Study (Rat Sciatic Nerve): 48 rats total.
  - 16 rats treated with subject device.
  - 16 rats treated with predicate device.
  - 16 rats treated with autograft control.
- Biocompatibility/Toxicology Studies:
  - Cytotoxicity: Cells (e.g., L-929 Mouse Fibroblast Cells).
  - Sensitization: Guinea Pig.
  - Intracutaneous Reactivity: Rabbits.
  - Acute Systemic Toxicity: Mice.
  - Subchronic Toxicity: Rabbits.
  - Genotoxicity: Bacterial strains (Salmonella typhimurium, Escherichia coli) and Mouse Lymphoma.
  - Material-Mediated Pyrogenicity: Rabbits.
  - Implantation (Local Tissue Reaction): Rabbits.
  - Haemocompatibility: Not specified (in vitro blood components).
  - Chronic Toxicity/Degradation: Rabbits.
Data Provenance: The studies were conducted in a laboratory/animal setting, not from a human retrospective or prospective clinical trial. The location (country) is not specified, but it's part of a US FDA submission.

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

Not Applicable. This is not an AI/ML study involving human interpretation of images or data that requires expert consensus for ground truth. The "ground truth" for these studies is established through direct measurements, biological assays, histological analyses, and observation of animal health/physiology by qualified laboratory personnel and veterinary pathologists, not human experts providing subjective assessments.

4. Adjudication Method for the Test Set

Not Applicable. Again, this is not an AI/ML study requiring adjudication of expert opinions. Results are based on objective laboratory measurements and pathological findings.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No. An MRMC study is designed for evaluating human reader performance, often with and without AI assistance, especially in diagnostic imaging. This document describes a medical device (nerve cuff), not an AI algorithm, and therefore, an MRMC study was not performed.

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

No. This is not an AI algorithm. "Standalone performance" is a concept applicable to AI systems.

7. The Type of Ground Truth Used

The "ground truth" for the various studies includes:
- Direct Physical Measurements: Suture pullout strength, compression resistance, kink resistance, permeability, hydrothermal transition temperature.
- Biological Assays: Cytotoxicity (cell lysis/toxicity), sensitization (dermal reactions), intracutaneous reactivity (irritation/toxicity from extract), acute systemic toxicity (mortality/systemic signs), subchronic toxicity (systemic signs), genotoxicity (mutagenesis), pyrogenicity (temperature rise).
- Histological and Histomorphometrical Methods: For the animal sciatic nerve study, evaluating nerve regeneration.
- Pathology: For implantation studies (local tissue reaction, resorption) and chronic toxicity.
- Observed Outcomes: Animal health, survival, signs of adverse reactions.

8. The Sample Size for the Training Set

Not Applicable. This document describes the testing of a physical medical device. It does not involve a "training set" as would be used for an AI/ML model.

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

Not Applicable. As there is no AI/ML training set, this question is not relevant.

Summary

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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

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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 (800) 638-2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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

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Indications for Use

510(k) Number (if known) K170656

Device Name Reinforced Flexible Collagen Nerve Cuff

Indications for Use (Describe)

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)

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510(k) SUMMARY

1. Applicant Information

Applicant Name:	Collagen Matrix, Inc.
Address:	15 Thornton Road
	Oakland, New Jersey 07436
Telephone:	(201) 405-1477
Fax:	(201) 405-1355
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

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).

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6. Summary/Comparison of Technical Characteristics

Parameter	Reinforced Flexible Collagen NerveCuff(This submission)	Flexible Collagen Nerve CuffK131541
Indications forUse	Intended for use in the managementof peripheral nerve injuries indiscontinuities where gap closure canbe achieved by flexion of the extremity(e.g., to prevent ingrowth of scartissue).	Intended for use in the management ofperipheral nerve injuries indiscontinuities where gap closure canbe achieved by flexion of the extremity(e.g., to prevent ingrowth of scartissue) or at the end of the nerve in thefoot to prevent the formation ofsymptomatic or painful neuroma.
Material	Type I collagen with absorbablepolymeric suture filament	Type I collagen
Source ofcollagen	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 length2.5 mm ID x 2.5 cm length3 mm ID x 2.5 cm length4 mm ID x 2.5 cm length5 mm ID x 2.5 cm length6 mm ID x 2.5 cm lengthAddition of a 3.0 cm length size for alldiameters.	2 mm ID x 2.5 cm length2.5 mm ID x 2.5 cm length3 mm ID x 2.5 cm length4 mm ID x 2.5 cm length5 mm ID x 2.5 cm length6 mm ID x 2.5 cm length
MechanicalStrength	Can be sutured	Can be sutured
pH	6 - 9	6 - 9
Resorbable	Yes	Yes
Crosslinked	Yes	Yes
Biocompatibility	Biocompatible	Biocompatible
Sterility	Sterile, SAL 10-6ETO sterilization	Sterile, SAL 10-6Gamma irradiation
Pyrogenicity	Non-pyrogenicEndotoxin ≤ 0.5 EU/ml	Non-pyrogenicEndotoxin ≤ 0.5 EU/ml
SingleUse/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

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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
PhysicalCharacterization	Suture pullout,compression resistance,kink resistance,permeability,hydrothermal transitiontemperature	Test results of the finished subject device arecomparable to the predicate device.
AnimalPerformance	Rat sciatic nerve study	Test results of the finished subject device arecomparable to the predicate device.
Cytotoxicity	Agarose Overlay, ISO10993-5	Non-cytotoxic; No evidence of causing anycell lysis or toxicity.
	MEM Elution Using L-929 Mouse FibroblastCells, ISO 10993-5	The test article scored '0' at 24, 48, and 72 ± 4hours and is considered non-cytotoxic underthe conditions of the test.
Sensitization	Guinea PigMaximization, ISO10993-10	No evidence of causing delayed dermalcontact sensitization in the guinea pig. Thetest article was not considered a sensitizer inthe guinea pig test.
IntracutaneousReactivity	Intracutaneous Study inRabbits, ISO 10993-10	Under the conditions of the study, there wasno irritation or toxicity from the extract injectedintracutaneously into rabbits.
Acute SystemicToxicity	Acute Systemic Toxicityin Mice, ISO 10993-11	No mortality or evidence of systemic toxicityup to 72 hours.
Subchronic(Systemic) Toxicity	Systemic Toxicity inRabbits, ISO 10993-11	No evidence of systemic toxicity or adversefindings specifically attributed to the test articleup to 13 weeks.
Genotoxicity	Bacterial ReverseMutation Study, ISO10993-3	Non-mutagenic to Salmonella typhimurium(strains TA97a, TA98, TA100, TA1535) and toEscherichia coli (strain WP2-uvra)
	Mouse LymphomaAssay, ISO 10993-3	Based on the criteria and conditions of thestudy protocol, the test article is considerednon-mutagenic (non-genotoxic and non-clastogenic)
Test	Test Method/Model	Results
Material-MediatedPyrogenicity	Rabbit Pyrogen study-USP <151>	Non-pyrogenic. None of the rabbitsadministered with the test article extract had atemperature rise ≥0.5°C at the observationtime points.
Implantation	Local Tissue Reaction ina Subcutaneous Implantin Rabbits, ISO 10993-6	The test article result was consideredacceptable at 2 weeks and 13 weeks whencompared to the control article.
Haemocompatibility	Hemolysis Assay –Extract Method, ASTMF756-13	The test article was considered non-hemolyticunder the test conditions employed.
Chronic ToxicityDegradation	Local Tissue Reactionand Resorption in aSubcutaneous Implantin Rabbits, ISO 10993-6	The test article result was consideredacceptable at 26 weeks when compared to thecontrol article. Resorption of test article andincorporation into new host collagen wasadvanced at 26 weeks.

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

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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.

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).