(214 days)
Collagen Dura Membrane is intended for use as a dura substitute for the repair of dura mater.
Collagen Dura Membrane is a white, nonfriable, conformable, membrane matrix consisting of highly purified collagen derived from bovine dermis. It is flexible and conforms to the contours of the defect site. The product's mechanical strength allows the membrane matrix to be sutured in place. Collagen Dura Membrane is supplied sterile, non-pyrogenic, in various sizes, and for single use only.
The Collagen Dura Membrane is a dura substitute for the repair of dura mater. The acceptance criteria and supporting study are described below, based on the provided FDA 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally framed as demonstrating "similarity to predicate device" or "not considered sensitizing," etc., in comparison to established standards and the predicate device (Durepair® Dura Regeneration Matrix).
| Test Parameter | Acceptance Criteria (Implied from comparison) | Reported Device Performance (Collagen Dura Membrane) |
|---|---|---|
| Material Properties | ||
| Dimensions | Similar to predicate device | Dimensions similar to predicate device |
| Suture Pullout Strength | Similar to predicate device | Suture strength similar to predicate device |
| Tensile Strength | Similar to predicate device | Tensile strength similar to predicate device |
| Conformability | Similar to predicate device | Conformability similar to predicate device |
| Hydrothermal Transition | Similar to predicate device | Hydrothermal transition temperature similar to predicate device. |
| Porosity/Permeability | Similar to predicate device | Permeability similar to predicate device |
| Biocompatibility | ||
| Cytotoxicity | Non-cytotoxic (as per ISO 10993-5) | Non-cytotoxic. |
| Sensitization | Not considered sensitizing (as per ISO 10993-10) | Not considered to be sensitizing. |
| Intracutaneous Reactivity | No erythema and no edema (as per ISO 10993-10) | No erythema and no edema from the test extract injected intracutaneously into the rabbits. |
| Acute Systemic Toxicity | No mortality or significant systemic toxicity (as per ISO 10993-11) | No mortality or evidence of significant systemic toxicity. |
| Genotoxicity | Non-mutagenic (as per ISO 10993-3) | Non-mutagenic to Salmonella typhimurium tester strains TA98, TA100, and TA1537, and to Escherichia coli strain WP2uvrA. None of the test article treatments induced substantial increases in the number of revertant colonies. Non-mutagenic (Mouse Lymphoma Assay). Levels of micronucleated cells within normal negative ranges. Non-mutagenic (In Vivo Mouse Micronucleus Assay). |
| Pyrogenicity | Non-pyrogenic (as per USP (151)) | The test article was judged as nonpyrogenic. |
| Implantation | Minimum tissue reaction up to 4 weeks, no adverse reaction (as per ISO 10993-6) | Minimum tissue reaction up to 4 weeks of implantation and no adverse tissue reaction to the host. |
| Subchronic Systemic | No evidence of systemic toxicity or adverse findings | There was no evidence of systemic toxicity or adverse findings attributed to the test article at 13 week time point. |
| Toxicity | at 13 weeks (as per ISO 10993-11) | |
| Chronic Toxicity | No evidence of systemic toxicity or adverse findings | There was no evidence of systemic toxicity or adverse findings attributed to the test article at 26 week time point. |
| at 26 weeks (as per ISO 10993-11) | ||
| Device Performance | ||
| Dura Repair & Resorption | Performance similar to predicate device | Subject device performed as well as the predicate device. |
| Resorption Profile | Verification of design criteria | Resorption profile verified design criteria. |
| Handling/Implantability | Handles as well as predicate device with typical surgical technique | Subject device handles as well as the predicate device using typical surgical technique for implantation. |
2. Sample size used for the test set and the data provenance
The document does not specify a separate "test set" in the context of clinical or independent evaluation using human readers. Instead, the study uses various in vitro and in vivo models for comparison to the predicate device and established standards.
- Animal Studies:
- Rabbit dural defect repair model: Used for dura repair and resorption comparison. Specific sample size not stated.
- Rat subcutaneous model: Used for resorption profile. Specific sample size not stated.
- Canine craniectomy model: Used for handling and implantability. Specific sample size not stated.
- Biocompatibility Studies: Specific animal numbers for each test (e.g., rabbits for intracutaneous reactivity, mice for systemic toxicity and micronucleus assay) are not explicitly detailed in this summary, but would have been part of the full study protocols.
- Data Provenance: The studies are non-clinical (in vitro, animal studies). The country of origin of the data is not specified but would typically be from the manufacturing or testing facilities commissioned by Collagen Matrix, Inc. All data is prospective, generated specifically for this submission.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not applicable. The studies performed are non-clinical, involving laboratory testing and animal models. There is no mention of human experts establishing ground truth for a "test set" in the context of diagnostic performance or clinical outcomes in the summary provided. Expert interpretation would primarily relate to pathologists or researchers evaluating animal tissues, but their number and specific qualifications are not detailed.
4. Adjudication method for the test set
Not applicable, as there is no mention of a "test set" requiring adjudication by human readers in this non-clinical submission summary.
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
Not applicable. This device is a physical dura substitute, not an AI-powered diagnostic or assistive tool. Therefore, an MRMC study related to AI assistance is not relevant.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. This device is a physical dura substitute, not an algorithm or software.
7. The type of ground truth used
The "ground truth" for the non-clinical studies was established through:
- Comparative measurements: Direct measurements of physical properties (dimensions, strength, conformity, temperature, permeability) compared to those of the predicate device.
- Standardized biological assays: Results from in vitro and in vivo biocompatibility tests were evaluated against established criteria from ISO 10993 series and USP standards (e.g., "non-cytotoxic," "not sensitizing," "no mortality or significant systemic toxicity").
- Histopathological evaluation: For implantation and animal efficacy studies, the "ground truth" would be the pathological assessment of tissue reaction, new dura formation, resorption, and overall device integration in the animal models.
- Direct observation: For handling and implantability, the "ground truth" was based on surgical observation during the canine model study.
8. The sample size for the training set
Not applicable. The device is a physical implant, not a machine learning algorithm requiring a "training set."
9. How the ground truth for the training set was established
Not applicable, as there is no training set for this type of device.
{0}------------------------------------------------
Image /page/0/Picture/1 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" arranged around the perimeter. Inside the circle is a stylized symbol featuring three overlapping human profiles facing to the right, with flowing lines extending from the bottom of the profiles.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 16, 2015
Collagen Matrix, Inc. Peggy Hansen Senior VP, Marketing and Regulatory Affairs 15 Thornton Road Oakland, New Jersey 07436
Re: K141608 Trade/Device Name: Collagen Dura Membrane Regulation Number: 21 CFR 882.5910 Regulation Name: Dura Substitute Regulatory Class: Class II Product Code: GXQ Dated: December 15, 2014 Received: December 17, 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 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
{1}------------------------------------------------
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 (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 yours,
Carlos L. Pena --S/^
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) K141608
Device Name Collagen Dura Membrane
Indications for Use (Describe)
Collagen Dura Membrane is intended for use as a dura substitute for the repair of dura mater.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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 PRAStaff@fda.hhs.gov
"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 RoadOakland, New Jersey 07436 |
| Telephone: | (201) 405-1477 |
| Fax: | (201) 405-1355 |
| Contact Person: | Peggy Hansen, RACVP, Clinical, Regulatory, QA, and Marketing |
| Date Prepared: | January 15, 2015 |
2. Name of the Device
Device Common Name: Device Trade Name: Device Classification Name: Dura Substitute Collagen Dura Membrane Dura Substitute 21 CFR 882.5910 Product Code GXQ Device Class II
3. Legally Marketed Devices to Which Substantial Equivalence is Claimed
Predicate Device(s):
Durepair® Dura Regeneration Matrix K052211
4. Description of the Device
Collagen Dura Membrane is a white, nonfriable, conformable, membrane matrix consisting of highly purified collagen derived from bovine dermis. It is flexible and conforms to the contours of the defect site. The product's mechanical strength allows the membrane matrix to be sutured in place. Collagen Dura Membrane is supplied sterile, non-pyrogenic, in various sizes, and for single use only.
5. Intended Use
Collagen Dura Membrane is intended for use as a dura substitute for the repair of dura mater.
{4}------------------------------------------------
6. Summary/Comparison of Technical Characteristics
Collagen Dura Membrane has been determined to be substantially equivalent to the predicate devices having similar technological characteristics as follows:
| Parameter | Collagen Dura Membrane(This submission) | Durepair® Dura RegenerationMatrix |
|---|---|---|
| Indications for Use | Intended for use as a durasubstitute for the repair of duramater. | Intended for use as a durasubstitute for the repair of duramater. |
| Collagen Source | Bovine dermis | Bovine dermis |
| Form | Membrane | Membrane |
| Color | White to off-white | White to off-white |
| Physical Integrity | Non-friable | Non-friable |
| Sizes | Variety of sizes | Variety of sizes |
| Suture Strength | Can be sutured | Can be sutured |
| 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 peel package | Double peel package |
7. Discussion of Non-clinical Testing
The substantial equivalence of Collagen Dura Membrane 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 quidelines 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
{5}------------------------------------------------
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
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 |
| Suture pulloutstrength | Internal test method usingmechanical test apparatus | Suture strength similar to predicate device |
| Tensilestrength | Internal test method usingmechanical test apparatus | Tensile strength similar to predicate device |
| Conformability | Internal test method tomeasure drape angle | Conformability similar to predicate device |
| Hydrothermaltransitiontemperature | Internal test method usingdifferential scanningcalorimeter | Hydrothermal transition temperature similarto predicate device. |
| Porosity /Permeability | Internal test method | Permeability similar to predicate device |
A series of in vitro and in vivo biocompatibility testing was performed to assess safety of the Collagen Dura Membrane as an implantable material. The biocompatibility testing performed is summarized in the table below.
| Test | Test Method/ Model | Results |
|---|---|---|
| Cytotoxicity | ISO Agarose Overlay Method -Extract, ISO 10993-5 | Non-cytotoxic. |
| Sensitization | Murine Local Lymph NodeAssay, ISO 10993-10 | Not considered to be sensitizing. |
| Intracutaneous Reactivity | Acute Intracutaneous Reactivityin Rabbit, ISO 10993-10 | No erythema and no edema from thetest extract injected intracutaneouslyinto the rabbits. |
| Acute | ISO Systemic Toxicity in Mice, | No mortality or evidence of significant |
{6}------------------------------------------------
| Test | Test Method/ Model | Results |
|---|---|---|
| SystemicToxicity | ISO 10993-11 | systemic toxicity. |
| Genotoxicity | Bacterial Reverse MutagenicStudy, ISO 10993-3 | Non-mutagenic to Salmonellatyphimurium tester strains TA98,TA100, and TA1537, and toEscherichia coli strain WP2uvrA. |
| Genotoxicity | Mouse Lymphoma Assay, ISO10993-3 | None of the test article treatmentsinduced substantial increases in thenumber of revertant colonies. Basedon the criteria and conditions of thestudy protocol, the test article isconsidered non-mutagenic. |
| Genotoxicity | In Vivo Mouse MicronucleusAssay, ISO 10993-3 | None of the mice treated with the testarticle preparations exhibited overtsigns of toxicity either immediatelypost-treatment or during the inductionperiod. The levels of micronucleatedcells were within normal negativeranges. Based on the criteria andconditions of the study protocol, thetest article is considered non-mutagenic. |
| Pyrogenicity | USP (151) Pyrogen Study -Material Mediated | The test article was judged asnonpyrogenic. |
| Implantation | Subcutaneous Implantation inRats, ISO 10993-6 | Minimum tissue reaction up to 4 weeksof implantation and no adverse tissuereaction to the host. |
| SubchronicSystemicToxicity | Subcutaneous Implantation inRabbits, ISO 10993-11 | There was no evidence of systemictoxicity or adverse findings attributed tothe test article at 13 week time point. |
| ChronicToxicity | Subcutaneous Implantation inRabbits, ISO 10993-11 | There was no evidence of systemictoxicity or adverse findings attributed tothe test article at 26 week time point. |
An animal efficacy study and additional animal studies were conducted to evaluate the device as compared to its predicate device. No clinical tests were performed on the product; however clinical history of the predicate device was referenced in the submission. The animal studies performed are summarized in the table below.
| Test | Test Method/ Model | Results |
|---|---|---|
| Dura RepairandResorption | Rabbit dural defect repair modelusing the subject device andpredicate device as a control | Subject device performed as well asthe predicate device |
| Resorption | Rat subcutaneous model usingthe subject device | Resorption profile verified designcriteria |
| Handling,Implantability | Canine craniectomy model forimplanting the subject deviceand predicate device | Subject device handles as well as thepredicate device using typical surgicaltechnique for implantation |
Viral inactivation studies were performed to ensure the viral safety of the product.
{7}------------------------------------------------
8. Conclusion of Non-clinical Studies
The predicate device was cleared based on the results of non-clinical data. Subject and predicate device performance data were compared to support the safety of the subject device and demonstrate that the Collagen Dura Membrane should perform as intended in the specified us conditions.
§ 882.5910 Dura substitute.
(a)
Identification. A dura substitute is a sheet or material that is used to repair the dura mater (the membrane surrounding the brain).(b)
Classification. Class II (performance standards).