Collagen Dural Regeneration Matrix

K150825 · Collagen Matrix, Inc. · GXQ · Nov 20, 2015 · Neurology

Device Facts

• Record ID: K150825
• Device Name: Collagen Dural Regeneration Matrix
• Applicant: Collagen Matrix, Inc.
• Product Code: GXQ · Neurology
• Decision Date: Nov 20, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 882.5910
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

Collagen Dural Regeneration Matrix is intended for use as a dura substitute for the repair of dura mater.

Device Story

Collagen Dural Regeneration Matrix is a white, non-friable, resorbable, porous type I collagen matrix derived from bovine Achilles tendon. It is designed to conform to the contours of a dural defect site. The device is supplied sterile and non-pyrogenic for single-use application. It functions as a physical barrier to facilitate dural repair and undergoes gradual resorption in vivo. It is intended for use by surgeons during neurosurgical procedures to repair the dura mater. The device provides a scaffold for tissue repair, helping to prevent cerebrospinal fluid (CSF) leakage and support healing at the surgical site.

Clinical Evidence

No clinical trials were performed. Evidence consists of non-clinical bench testing (dimensions, pH, tensile strength, conformability, hydrothermal transition, liquid permeability, burst strength) and biocompatibility testing (ISO 10993 series: cytotoxicity, sensitization, intracutaneous reactivity, systemic toxicity, genotoxicity, pyrogenicity, muscle/subcutaneous implantation). An animal efficacy study in a rabbit dural defect model compared the device to the predicate for repair and resorption. Clinical history of the predicate device was referenced.

Technological Characteristics

Material: Type I collagen from bovine Achilles tendon. Form: Porous, sponge-like matrix with one smooth surface. Properties: Non-friable, conformable, resorbable. Sterilization: Sterile (SAL 10^-6). Standards: ISO 22442-1/2/3 (animal tissues), ISO 10993-3/5/6/10/11 (biocompatibility).

Indications for Use

Indicated for the repair of dura mater in patients requiring a dura substitute.

Regulatory Classification

Identification

A dura substitute is a sheet or material that is used to repair the dura mater (the membrane surrounding the brain).

Predicate Devices

• DuraGen Plus® Dural Regeneration Matrix (K032693)

Submission Summary (Full Text)

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

November 20, 2015

Collagen Matrix, Inc. Ms. Gloria Zuclich Senior Manager of Regulatory Affairs 15 Thornton Road Oakland, New Jersey 07436

Re: K150825

Trade/Device Name: Collagen Dural Regeneration Matrix Regulation Number: 21 CFR 882.5910 Regulation Name: Dura Substitute Regulatory Class: Class II Product Code: GXQ Dated: November 13, 2015 Received: November 16, 2015

Dear Ms. Zuclich:

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 (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in

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the quality systems (OS) 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 yours,

Carlos L. Pena -S FD/△

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) K150825

Device Name Collagen Dural Regeneration Matrix

Indications for Use (Describe)

Collagen Dural Regeneration Matrix is intended for use as a dura substitute for the repair of dura mater.

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

| <span style="font-family: Arial;">☑</span> 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<br>Oakland, New Jersey 07436 USA |
| Telephone: | [phone] Ext. 317 |
| Fax: | [phone] |
| Contact Person: | Gloria Zuclich<br>Senior Manager of Regulatory Affairs |
| Date Prepared: | November 19, 2015 |

#### 2. Name of the Device

| Device Trade Name: | Collagen Dural Regeneration Matrix |
|-----------------------------|-------------------------------------------------------------------|
| Device Common Name: | Collagen Dura Substitute |
| Device Classification Name: | Dura Substitute |
| | Regulation Number 882.5910<br>Product Code GXQ<br>Device Class II |

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

DuraGen Plus® Dural Regeneration Matrix Predicate Device(s): K032693

#### 4. Description of the Device

Collagen Dural Regeneration Matrix is a white, non-friable, resorbable and biocompatible type I collagen matrix made from purified bovine Achilles tendon. Collagen Dural Regeneration Matrix is a porous, sponge-like collagen matrix with one smooth surface that conforms to the contours of the defect site. It is supplied sterile, non-pyrogenic, in various sizes, and for single use only.

#### 5. Intended Use

Collagen Dural Regeneration Matrix is intended for use as a dura substitute for the repair of dura mater.

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

Collagen Dural Regeneration Matrix has been determined to be substantially equivalent to the predicate device having similar technological characteristics as follows:

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| Parameter | Collagen Dural Regeneration<br>Matrix (This submission) | DuraGen Plus® Dural Graft<br>Matrix |
|---------------------|---------------------------------------------------------------------------|---------------------------------------------------------------------------|
| 510(k) | K150825 | K032693 |
| Indications for Use | Intended for use as a dura<br>substitute for the repair of dura<br>mater. | Intended for use as a dura<br>substitute for the repair of dura<br>mater. |
| Collagen Source | Bovine Achilles tendon | Bovine Achilles tendon |
| Form | Porous Collagen Matrix | Porous Collagen Matrix |
| Color | White to off-white | White to off-white |
| Physical Integrity | Non-friable | Non-friable |
| Sizes | Variety of sizes | Variety of sizes |
| Conformability | Conformable | Conformable |
| Biocompatibility | Biocompatible | Biocompatible |
| In Vivo Stability | Gradual resorption | Gradual resorption |
| Sterility | Sterile, SAL 10-6 | Sterile, SAL 10-6 |
| Pyrogenicity | Non-pyrogenic | Non-pyrogenic |
| Single Use/Reuse | Single use only | Single use only |
| Packaging | Double blister | Double blister |

# 7. Discussion of Non-clinical Testing

The substantial equivalence of Collagen Dural Regeneration Matrix and its predicate was demonstrated based on in vitro characterization studies, biocompatibility studies, and an animal efficacy study.

Non-clinical testing was performed in accordance with FDA recognized consensus standards and FDA guidelines as follows:

FDA Guidance Document entitled, "Guidance document for Dura Substitute Device: Guidance for Industry", issued on November 9, 2000

ISO 22442-1 Animal Tissues and Their Derivatives Utilized in the Manufacture of Medical Devices – Part 1 Analysis and Risk Management

ISO 22442-2 Animal Tissues and Their Derivatives Utilized in the Manufacture of Medical Devices - Part 2 Controls on Sourcing, Collection, and Handling

ISO 22442-3 Animal Tissues and Their Derivatives Utilized in the Manufacture of Medical Devices – Part 3 Validation of the Elimination and/or Inactivation of Viruses and Transmissible Agents

ISO 10993-3:2009 Biological Evaluation of Medical Devices- Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity

ISO 10993-5:2009 Biological Evaluation of Medical Devices- Part 5: Tests for in vitro cytotoxicity

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ISO 10993-6:2009 Biological Evaluation of Medical Devices- Part 6: Test for local effects after implantation

ISO 10993-10:2009 Biological Evaluation of Medical Devices- Part 10 Test for local effects after implantation

ISO 10993-11:2009 Biological Evaluation of Medical devices - Part 11 Tests for systemic toxicity

## Non-clinical Testing Conducted

In vitro product characterization testing was performed to demonstrate substantial equivalence of the subject device to its predicate device. A series of bench tests were conducted to evaluate material properties, biological properties, chemical and physical properties. The comparative bench testing is summarized in the table below.

| Test | Test Method | Results |
|-------------------------------------------|--------------------------------------------------------------------|---------------------------------------------------------------------|
| Dimensions | Measurements | Dimensions similar to predicate device |
| pH | Internal test method using<br>pH meter | pH similar to predicate device |
| Tensile<br>strength | Internal test method using<br>mechanical test apparatus | Tensile strength similar to predicate device |
| Conformability | Internal test method to<br>measure drape angle | Conformability similar to predicate device |
| Hydrothermal<br>transition<br>temperature | Internal test method using<br>differential scanning<br>calorimeter | Hydrothermal transition temperature<br>similar to predicate device. |
| Liquid<br>Permeability | Internal test method to<br>measure permeability to<br>liquid | Minimally permeable; similar to predicate |
| Burst strength | Internal test method to<br>measure burst strength | Adequate for cerebrospinal fluid (CSF)<br>pressure |

A series of in vitro and in vivo biocompatibility testing was performed to assess safety of the Collagen Dural Regeneration Matrix as an implantable material. The biocompatibility testing performed is summarized in the table below.

| Test | Test Method/ Model | Results |
|------------------------------|---------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Cytotoxicity | Agarose Overlay, ISO 10993-5 | Non-cytotoxic |
| Sensitization | Guinea Pig Maximization, ISO<br>10993-10 | Under the conditions of this protocol,<br>the test article did not elicit a<br>sensitization response. |
| Intracutaneous<br>Reactivity | Intracutaneous Reactivity in<br>Rabbit, ISO 10993-10 | Polar Extract<br>Under the conditions of the study,<br>there was no erythema and no edema<br>from the test extract injected<br>intracutaneously into the rabbits. |
| Test | Test Method/ Model | Results |
| | | Non-polar Extract<br>Under the conditions of the study,<br>there was no to very slight erythema or<br>edema from the extract injected<br>intracutaneously into rabbits. |
| Acute Systemic<br>Toxicity | Acute Systemic Toxicity in<br>Mice, ISO 10993-11 | No mortality or evidence of systemic<br>toxicity. |
| Genotoxicity | Bacterial Reverse Mutagenic<br>Study, ISO 10993-3 | Non-mutagenic to Salmonella<br><i>typhimurium</i> (Test Strains: TA98,<br>TA1535, and TA1537) and to<br><i>Escherichia coli</i> (Test Strain WP2uvrA) |
| Genotoxicity | Mouse Lymphoma Assay, ISO<br>10993-3 | The test article extracts did not cause<br>a two-fold or greater increase in the<br>mean mutant frequency of the<br>L5178Y/TK+/- cell line either in the<br>presence or absence of metabolic<br>activation. The test article is<br>considered non-mutagenic. |
| Pyrogenicity | USP (151) Pyrogen Study –<br>Material Mediated | The test article was judged as<br>nonpyrogenic. |
| Muscle<br>Implantation | Muscle Implantation Study in<br>Rabbits, 2 weeks, ISO 10993-6 | The macroscopic reaction was not<br>significant as compared to the sponsor<br>provided control article or to the<br>negative control article.<br>Microscopically, the test article was<br>classified as a non-irritant as<br>compared to the sponsor provided<br>control article and as a slight irritant as<br>compared to the negative control<br>article. |
| Subchronic<br>Toxicity | Subcutaneous Implantation in<br>Rabbits, ISO 10993-11 | Under the conditions of the 13-week<br>study, there was no evidence of<br>systemic toxicity or adverse findings<br>attributed to the test article when<br>compared with the predicate control. |
| Chronic<br>Toxicity | Subcutaneous Implantation in<br>Rabbits, ISO 10993-11 | Under the conditions of the 26-week<br>subcutaneous implant toxicity study,<br>there was no evidence of systemic<br>toxicity or adverse findings attributed to<br>the test article. Based upon the<br>differences between the Test Article<br>Group Average Irritation Scores, the<br>test article was considered non-irritant<br>when compared to the predicate<br>control at 26 weeks. |

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An animal efficacy study utilizing a rabbit dural defect repair model was conducted to evaluate the device as compared to its predicate device with regards to dura repair and resorption. No clinical tests were performed on the product; however clinical history of the predicate device was referenced in the submission.

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A Viral inactivation study was performed to ensure the viral safety of the product.

# 8. Conclusion of Non-clinical Studies

The predicate device was cleared based on the results of non-clinical data. The subject device demonstrates equivalence to the predicate device.