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 Description

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.

AI/ML Overview

The provided text describes a 510(k) summary for the Flexible Collagen Nerve Cuff, which is a medical device. The document primarily focuses on demonstrating substantial equivalence to a predicate device for expanded indications, rather than conducting a de novo study with acceptance criteria and device performance evaluation in the typical sense of AI/ML device studies.

Therefore, many of the requested categories related to AI/ML device studies (like sample size for test set, number of experts for ground truth, adjudication method, MRMC study, standalone performance, training set size, and ground truth for training set) are not applicable or cannot be extracted from this document, as it concerns a physical medical device.

Here's the information that can be extracted from the document regarding its "acceptance criteria" (understood as demonstrating safety and equivalence) and the "study" (clinical and non-clinical evaluations):

1. Table of "Acceptance Criteria" (demonstrated safety and equivalence) and the "Reported Device Performance":

Since this is a physical device seeking expanded indications based on substantial equivalence, the "acceptance criteria" are implied by demonstrating equivalence to predicate devices and meeting safety standards. The reported "performance" is primarily for the clinical outcome associated with the expanded indication.

Parameter	Acceptance Criteria (Implied by equivalence & safety)	Reported Device Performance
Expanded Indication Performance (Pain Reduction for Neuromas)	Substantially equivalent to Silastic® Nerve Cuff and clinically significant improvement over excision-only for pain reduction in foot neuromas.	93% success rate of reducing pain for the treatment of neuroma in the foot. Met substantial equivalence to predicate and showed significant improvement over control group in a literature review/meta-analysis.
Non-clinical Physical Properties (Suture Strength, Kink Resistance, Permeability, Hydrothermal Transition Temperature)	Equivalent to predicate device (Collagen Nerve Cuff K012814).	Characterization test results "equivalent to those of the predicate device."
Biocompatibility (Cytotoxicity, Sensitization, Intracutaneous Reactivity, Acute Systemic Toxicity, Genotoxicity (Bacterial Reverse Mutation, Mouse Lymphoma, Mouse Micronucleus), Pyrogenicity, Muscle Implantation, Subacute/Subchronic/Chronic Toxicity)	Pass all applicable FDA Blue Book Memorandum G95-1 and ISO 10993-1 testing.	Non-cytotoxic, Non-sensitizer, Non-irritant, Non-toxic (acute, subacute, subchronic, chronic), Non-mutagenic, Non-pyrogenic.
Viral Safety	Ensure viral safety.	Viral inactivation studies performed to ensure viral safety.

2. Sample size used for the test set and the data provenance:

Sample Size (Clinical Study): 50 patients (30 right, 20 left sides; 1 patient bilateral)
Number of Nerves Treated: 60 nerves
Data Provenance: Not explicitly stated, but implies a prospective or retrospective single-center clinical study for the 50 patients who underwent surgery with the device. The meta-analysis involved "published studies."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not Applicable in the AI/ML sense. The clinical study evaluated patient-reported pain reduction, not expert-adjudicated images or diagnoses. The "ground truth" for success was the patient's self-reported pain score change.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not Applicable in the AI/ML sense. The clinical study relied on patient self-reported pain scores.

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, an MRMC comparative effectiveness study was not done. This is a physical device, not an AI/ML diagnostic tool involving human readers.
However, a clinical literature review and meta-analysis was conducted to compare the device's clinical performance (pain reduction) to its predicate device (Silastic Nerve Cuff) and nerve excision alone.
- Effect Size: The analysis concluded that the Flexible Collagen Nerve Cuff "performs substantially equivalent to its predicate device (Silastic Nerve Cuff) with respect to reduction of pain post-operatively." Additionally, "both devices show clinically significant improvement in pain reduction over the excision-only control group." No specific numerical effect size (e.g., odds ratio, mean difference) is provided for the improvement.

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

Not Applicable. This is a physical device, not an algorithm. Its performance is inherent to its material properties and clinical application.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

Patient-reported outcomes data: For the clinical study, the "ground truth" for effectiveness was the patient's self-reported pain score (1-10 scale) before and after surgery.

8. The sample size for the training set:

Not Applicable. This is a physical device, not an AI/ML algorithm that requires a training set.

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

Not Applicable.

Summary

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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:	(201) 405-1477
Fax:	(201) 405-1355
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.

5. Indications for Use / Intended Use

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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 NerveCuff(This submission)	Collagen Nerve CuffK012814	Silastic® Nerve Cuff
Indications for Use	Intended for use in themanagement ofperipheral nerve injuriesin discontinuities wheregap closure can beachieved by flexion ofthe extremity (e.g., toprevent ingrowth of scartissue) or at the end ofthe nerve in the foot toreduce the formation ofsymptomatic or painfulneuroma.	Intended for use in therepair of peripheral nervediscontinuities where gapclosure can be achievedby flexion of theextremity.	Intended to be used toencase a nerve for aid inrepairing the nerve (e.g., toprevent ingrowth of scartissue) and for capping theend of the nerve to preventthe formation of neuroma(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 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	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	3.3 mm ID x 1.0 cm length4.1 mm ID x 1.0 cm length4.8 mm ID x 1.0 cm length5.3 mm ID x 1.3 cm length6.1 mm ID x 1.3 cm length7.1 mm ID x 1.3 cm length7.9 mm ID x 1.5 cm length8.6 mm ID x 1.5 cm length9.9 mm ID x 1.5 cm length10.7 mm ID x 1.5 cm length11.7 mm ID x 1.8 cm length13.7 mm ID x 1.8 cm length
MechanicalStrength	Can be sutured	Can be sutured	Can be sutured
Resorbable	Yes	Yes	No
Crosslinked	Yes	Yes	No
Porosity/Permeability	Semi-permeable.Permeable to nutrientsand macromolecules	Semi-permeablePermeable to nutrientsand macromolecules	Non-permeable
Biocompatibility	Biocompatible	Biocompatible	Biocompatible
Sterility	Sterile, SAL 10-6Gamma irradiation	Sterile, SAL 10-6Gamma irradiation	Sterile
Pyrogenicity	Non-pyrogenicEndotoxin ≤ 0.5 EU/ml	Non-pyrogenicEndotoxin ≤ 0.5 EU/ml	Unknown
Single Use/Reuse	Single use only	Single use only	Single use only
Parameter	Flexible Collagen NerveCuff(This submission)	Collagen Nerve CuffK012814	Silastic® Nerve Cuff
Packaging	Double peel package	Double peel package	Sterile vials of distilledwater

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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 -AgaroseOverlay	No evidence of causing any cell lysis or toxicity.	Non-cytotoxic
Sensitization -Guinea PigMaximization	No evidence of causing delayed dermal contactsensitization in the guinea pig. The test articlewas not considered a sensitizer in the guineapig test.	Non-sensitizer
IntracutaneousReactivity	Under the conditions of the study, there was noirritation or toxicity from the extract injectedintracutaneously into rabbits.	Non-irritant, non-toxic
Acute SystemicToxicity	No mortality or evidence of systemic toxicity	Non-toxic(acute systemic)
Genotoxicity -BacterialReverseMutation	Non-mutagenic to Salmonella typhimurium andto Escherichia coli strain WP2uvra	Non-mutagenic
MouseLymphomaAssay	None of the test article treatments inducedsubstantial increases in the number of revertantcolonies.	Non-mutagenic
In Vivo MouseMicronucleusAssay	None of the mice treated with the test articlepreparations exhibited overt signs of toxicityeither immediately post-treatment or during theinduction period. The levels of micronucleatedcells 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 -Rabbit Pyrogen	Non-pyrogenic	Non-pyrogenic
MuscleImplantation	The macroscopic reaction was not significantcompared with the USP negative controlimplant material. Microscopically, the testarticle was classified as a nonirritant ascompared to the USP negative control article.	Non-irritant
Subacute/Subchronic/Chronic Toxicity	Minimum tissue reaction up to 24 weeks ofimplantation and no adverse tissue reaction tothe host.	Non toxic(subacute, subchronic,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 (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" (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 (800) 638-2041 or (301) 796-7100 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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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).