(238 days)
Collagen Dural Regeneration Matrix is intended for use as a dura substitute for the repair of dura mater.
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.
This document is a 510(k) premarket notification for a medical device called "Collagen Dural Regeneration Matrix." This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving novel effectiveness or clinical superiority. Therefore, the information provided is geared towards comparing the new device to an existing one.
Here's an analysis of the acceptance criteria and supporting studies, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" for performance in a quantitative manner as one might find for a diagnostic device. Instead, it demonstrates substantial equivalence by comparing various parameters of the new device to its predicate. The "results" in the tables below effectively serve as the device performance against the implicit acceptance criteria of being "similar to predicate device" or "adequate."
| Parameter | Acceptance Criteria (Implied) | Reported Device Performance (Collagen Dural Regeneration Matrix) |
|---|---|---|
| General Characteristics (from Section 6) | ||
| Indications for Use | Same as predicate | Intended for use as a dura substitute for the repair of dura 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 |
| In Vitro Characterization (from Section 7) | ||
| Dimensions | Similar to predicate | Dimensions similar to predicate device |
| pH | Similar to predicate | pH similar to predicate device |
| Tensile strength | Similar to predicate | Tensile strength similar to predicate device |
| Conformability | Similar to predicate | Conformability similar to predicate device |
| Hydrothermal transition temperature | Similar to predicate | Hydrothermal transition temperature similar to predicate device. |
| Liquid Permeability | Minimally permeable; similar to predicate | Minimally permeable; similar to predicate |
| Burst strength | Adequate for cerebrospinal fluid (CSF) pressure | Adequate for cerebrospinal fluid (CSF) pressure |
| Biocompatibility (from Section 7) | ||
| Cytotoxicity | Non-cytotoxic | Non-cytotoxic |
| Sensitization | No sensitization response | No sensitization response |
| Intracutaneous Reactivity | No erythema and no edema (for polar extract); No to very slight erythema or edema (for non-polar extract) | Met criteria |
| Acute Systemic Toxicity | No mortality or evidence of systemic toxicity | No mortality or evidence of systemic toxicity |
| Genotoxicity (Bacterial Reverse Mutagenic) | Non-mutagenic | Non-mutagenic to Salmonella typhimurium and Escherichia coli |
| Genotoxicity (Mouse Lymphoma Assay) | Non-mutagenic | Non-mutagenic (no two-fold or greater increase in mean mutant frequency) |
| Pyrogenicity | Non-pyrogenic | Non-pyrogenic |
| Muscle Implantation | Not significant macroscopic reaction; Non-irritant (microscopically vs. control); Slight irritant (microscopically vs. negative control) | Achieved |
| Subchronic Toxicity | No evidence of systemic toxicity or adverse findings | No evidence of systemic toxicity or adverse findings attributed to the test article when compared with the predicate control. |
| Chronic Toxicity | No evidence of systemic toxicity or adverse findings | No evidence of systemic toxicity or adverse findings attributed to the test article; non-irritant when compared to the predicate control at 26 weeks. |
2. Sample Size Used for the Test Set and Data Provenance
This is not applicable in the context of this 510(k) premarket notification in the way it would be for an AI/diagnostic device.
- Test Set: The "test set" here refers to the actual Collagen Dural Regeneration Matrix devices and components subjected to various in vitro and in vivo tests. The exact number of samples used for each bench test is not specified in the summary, but it would typically involve replicates to ensure statistical validity.
- Data Provenance:
- In Vitro Characterization: Laboratory internal testing data.
- Biocompatibility: Laboratory testing following ISO standards.
- Animal Efficacy Study: Conducted using a rabbit model.
- Retrospective/Prospective: The testing described is prospective, in that samples of the new device were specifically manufactured and tested for this submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- This is not applicable for a device like a dural regeneration matrix. Ground truth for its performance is established through physical, chemical, and biological testing as outlined in the tables, rather than expert interpretation of images or clinical data.
- For the animal study, the assessment of dura repair and resorption would typically be conducted by veterinary pathologists or qualified researchers. No specific number or qualifications are given in this summary.
4. Adjudication Method for the Test Set
- Not applicable as the ground truth is established through objective laboratory and animal testing, not human readers or consensus.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of AI Improvement
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that analyze images or data for human interpretation, often involving AI. The Collagen Dural Regeneration Matrix is a physical implant, not a diagnostic tool incorporating AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- No, a standalone algorithm performance study was not done. This is not an AI device.
7. The Type of Ground Truth Used
The ground truth for the device's performance and safety was established through:
- Physical and Chemical Properties: Measured quantitatively (e.g., pH, tensile strength, burst strength, dimensions, permeability, hydrothermal transition temperature) and qualitatively (e.g., conformability, color, physical integrity).
- Biocompatibility Endpoints: Based on standardized in vitro and in vivo assays (e.g., cytotoxicity, sensitization, systemic toxicity, genotoxicity, pyrogenicity, implantation responses).
- Animal Study Outcomes: Observation and assessment of dura repair and resorption in a rabbit model.
8. The Sample Size for the Training Set
- Not applicable. This device does not involve a "training set" in the context of machine learning or AI.
9. How the Ground Truth for the Training Set Was Established
- Not applicable, as there is no training set for this device.
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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 (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 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) |
|---|
| ------------------------------------------------- |
| ☑ 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 RoadOakland, New Jersey 07436 USA |
| Telephone: | (201) 405-1477 Ext. 317 |
| Fax: | (201) 405-1355 |
| Contact Person: | Gloria ZuclichSenior 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 882.5910Product Code GXQDevice 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 RegenerationMatrix (This submission) | DuraGen Plus® Dural GraftMatrix |
|---|---|---|
| 510(k) | K150825 | K032693 |
| 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 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 usingpH meter | pH 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 temperaturesimilar to predicate device. |
| LiquidPermeability | Internal test method tomeasure permeability toliquid | Minimally permeable; similar to predicate |
| Burst strength | Internal test method tomeasure burst strength | Adequate for cerebrospinal fluid (CSF)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, ISO10993-10 | Under the conditions of this protocol,the test article did not elicit asensitization response. |
| IntracutaneousReactivity | Intracutaneous Reactivity inRabbit, ISO 10993-10 | Polar ExtractUnder the conditions of the study,there was no erythema and no edemafrom the test extract injectedintracutaneously into the rabbits. |
| Test | Test Method/ Model | Results |
| Non-polar ExtractUnder the conditions of the study,there was no to very slight erythema oredema from the extract injectedintracutaneously into rabbits. | ||
| Acute SystemicToxicity | Acute Systemic Toxicity inMice, ISO 10993-11 | No mortality or evidence of systemictoxicity. |
| Genotoxicity | Bacterial Reverse MutagenicStudy, ISO 10993-3 | Non-mutagenic to Salmonellatyphimurium (Test Strains: TA98,TA1535, and TA1537) and toEscherichia coli (Test Strain WP2uvrA) |
| Genotoxicity | Mouse Lymphoma Assay, ISO10993-3 | The test article extracts did not causea two-fold or greater increase in themean mutant frequency of theL5178Y/TK+/- cell line either in thepresence or absence of metabolicactivation. The test article isconsidered non-mutagenic. |
| Pyrogenicity | USP (151) Pyrogen Study –Material Mediated | The test article was judged asnonpyrogenic. |
| MuscleImplantation | Muscle Implantation Study inRabbits, 2 weeks, ISO 10993-6 | The macroscopic reaction was notsignificant as compared to the sponsorprovided control article or to thenegative control article.Microscopically, the test article wasclassified as a non-irritant ascompared to the sponsor providedcontrol article and as a slight irritant ascompared to the negative controlarticle. |
| SubchronicToxicity | Subcutaneous Implantation inRabbits, ISO 10993-11 | Under the conditions of the 13-weekstudy, there was no evidence ofsystemic toxicity or adverse findingsattributed to the test article whencompared with the predicate control. |
| ChronicToxicity | Subcutaneous Implantation inRabbits, ISO 10993-11 | Under the conditions of the 26-weeksubcutaneous implant toxicity study,there was no evidence of systemictoxicity or adverse findings attributed tothe test article. Based upon thedifferences between the Test ArticleGroup Average Irritation Scores, thetest article was considered non-irritantwhen compared to the predicatecontrol 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.
§ 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).