Durepair® Dura Regeneration Matrix is a collagen implant for the repair of defects in the dura mater. Durepair is supplied sterile, in a double-peel package, and is intended for single (one-time) use-only. Durepair is available in a variety of sizes intended to be cut by the surgeon to the desired shape.

AI/ML Overview

The document describes the Durepair Dura Regeneration Matrix, a collagen implant for repairing dura mater defects. This is a 510(k) submission, meaning the device is seeking clearance by demonstrating substantial equivalence to a legally marketed predicate device, rather than proving de novo safety and effectiveness.

Here's an analysis of the acceptance criteria and supporting studies, based on the provided text:

Key Takeaway: The entire submission focuses on demonstrating that a manufacturing process change for the Proposed Durepair Device does not alter its fundamental technological characteristics, material, indications for use, or safety and effectiveness compared to the Predicate Durepair Device. Therefore, the "acceptance criteria" discussed are largely related to ensuring the proposed device performs comparably to the predicate across various physical, mechanical, and biological properties.

1. Table of Acceptance Criteria and Reported Device Performance

The document provides "Table 2 – Summary of Bench Top Testing" and "Table 3 – Summary of Biocompatibility Testing" which directly address acceptance criteria and the performance of the Proposed Durepair device.

Test	Acceptance Criteria (Test Method Summary)	Reported Device Performance (Results for Proposed Durepair device)
Bench Top Testing
Sizes	Specified length/width tolerance of ± 5%. Measured with digital calipers.	All samples met the acceptance criteria.
Tensile Strength	Average 5 MPa minimum. Sampled from two thinnest corners.	All samples met the acceptance criteria.
Tensile Stiffness	Average 225 MPa maximum. Sampled from two thinnest corners.	All samples met the acceptance criteria.
Suture Retention Strength	Minimum of 5 N at a pull rate of 20mm/min, 3mm suture bite (polypropylene 4-0 suture). Two samples from thinnest areas.	All samples met the acceptance criteria.
Wet Shrink Temperature	58° - 67° C (in-process specification) via Differential Scanning Colorimeter.	All samples met the acceptance criteria.
Pore Size	No visible through pores.	All samples met the acceptance criteria.
Hydration Rate	Time to hydrate ≤ 3 minutes using saline solution at room temperature.	All samples met the acceptance criteria.
Histology (Wet EBM)	No cells or cellular/nuclear debris evident.	All samples met the acceptance criteria.
Safety (Pyrogenicity)	Non-pyrogenic (≤ 2.15 EU/device). No bacterial endotoxins per production lot.	All samples met the acceptance criteria.
Bioburden	No bioburden observed in final rinse water (0 CFUs for each lot).	All samples met the acceptance criteria.
Biocompatibility Testing
Calcification	No calcification. Samples implanted in weanling rats for 4 weeks; explants grossly and microscopically examined.	Pass. No calcification was present.
Cytotoxicity	Per ISO 10993-5. Test item non-cytotoxic if no cultures show > mild reactivity (grade 2). Mouse fibroblasts to MEM elution of product.	Pass. None of the cultures showed > grade 2 reactivity.
Skin Sensitization Study (Saline & Cottonseed Oil Extraction)	Per ISO 10993-10. No significant dermal contact sensitization. Guinea pig maximization test.	Pass. All test animals scored a 0 and had no significant dermal contact sensitization.
Irritation Study, Intracutaneous Injection (Saline & Cottonseed Oil Extraction)	Per ISO 10993-10. Mean reaction scores for test articles < 1.0. Evaluated in rabbits.	Pass. Mean reaction scores for test articles were < 1.0.
Acute Systemic Toxicity, Systemic Injection (Saline & Cottonseed Oil Extraction)	Per ISO 10993-11. No evidence of mortality or acute systemic toxicity. Evaluated in mice.	Pass. No test or control animals showed signs of toxicity.
Hemolysis, Rabbit Blood	Per ISO 10993-4. Corrected % hemolytic index for direct and indirect contact < 5%.	Pass. Corrected % hemolytic index for direct and indirect contact was < 5%.
Intramuscular Implantation Study (4 weeks & 12 weeks)	Per ISO 10993-6. Must be non-reactive. Evaluated local tissue responses in rat intramuscular model.	Pass. No reaction was seen in the samples.
Genotoxicity, Ames Reverse Mutation Assay	Per ISO 10993-3. No 2X, or greater, increase in mean number of revertants compared to negative control. Evaluated in bacteria.	Pass. None of the test article extracts induced a significant increase in number of revertants compared to the negative control.

2. Sample Size for Test Set and Data Provenance

Sample Size for Test Set: The document does not explicitly state the exact number of samples (e.g., individual devices or specimens) used for each bench or biocompatibility test. It often refers to "All samples," "each skin," or "each lot."
- For Sizes, "All samples met the acceptance criteria, measured with digital calipers and were inspected 100%." This implies every unit or a statistically representative sample for dimension checking.
- For Tensile Strength and Tensile Stiffness, "All skins were sampled at the two thinnest corners of each skin."
- For Suture Retention Strength, "Two suture retention samples were taken from the thinnest (weakest) areas of each skin."
- For Safety (Pyrogenicity) and Bioburden, "per each production lot."
- For Calcification, "Samples implanted into weanling rats."
- For Cytotoxicity, "Lots tested."
- For animal studies (Skin Sensitization, Irritation, Acute Systemic Toxicity, Intramuscular Implantation), it refers to "test animals," "rabbits," "mice," "weanling rats," but does not explicitly state the number of animals per test.
Data Provenance (Country of Origin, Retrospective/Prospective): The document does not provide information on the country of origin of the data or whether the studies were retrospective or prospective. Given the nature of bench and biocompatibility testing for a 510(k) submission, these are typically prospective laboratory/animal studies conducted by the manufacturer or contracted labs to evaluate the specific proposed device.

3. Number of Experts and Qualifications for Ground Truth

This device is not an AI/ML-based diagnostic or imaging device, so the concept of "ground truth established by experts" in the context of diagnostic performance does not directly apply here.
The "ground truth" for the tests performed (e.g., tensile strength, biological reaction) is derived from objective, quantitative measurements (e.g., MPa, N, °C, % hemolytic index) and standardized histological or macroscopic observations following established ISO or internal test methods.
For histological evaluations (e.g., Calcification, Intramuscular Implantation), implicit "experts" would be pathologists or histotechnicians interpreting the tissue slides, but their number or qualifications are not specified, as this is standard practice for such tests.

4. Adjudication Method for Test Set

Not applicable in the context of this device. Adjudication methods (like 2+1 or 3+1) are typically used in clinical studies or reader studies for diagnostic devices where disagreement among human readers needs to be resolved to establish a consensus ground truth. Here, the tests are primarily objective measurements or standardized biological assays.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. This type of study assesses how human readers perform with vs. without AI assistance, which is relevant for diagnostic AI tools. The Durepair Dura Regeneration Matrix is a physical implant, not an AI diagnostic.
The study design focuses on bench testing (physical and mechanical properties) and biocompatibility testing to demonstrate the proposed device is substantially equivalent to a predicate, especially given a manufacturing process change.

6. Standalone (Algorithm Only) Performance

Not applicable. This is a physical medical implant, not a software algorithm or AI device.

7. Type of Ground Truth Used

The "ground truth" for these tests comes from:

Objective Measurements: Directly measured quantitative values for physical and mechanical properties (e.g., length, width, tensile strength, stiffness, suture retention, shrink temperature, hydration rate).
Standardized Analytical Results: Quantitative results from analytical methods (e.g., pyrogenicity [EU/device], bioburden [CFU]).
Histopathology/Biological Assay Standards: Qualitative and semi-quantitative assessments based on established biological safety standards (ISO 10993 series) interpreted by trained personnel (e.g., absence of cells/debris, calcification, specific grades of reactivity, absence of toxicity/sensitization, hemolytic index).
- For calcification, histology images were likely the "ground truth."
- For cytotoxicity, the "grade of reactivity" based on cell culture observations.
- For genotoxicity, the "number of revertants" compared to controls.

8. Sample Size for the Training Set

Not applicable. This is not an AI/ML device that requires a training set. The "Proposed Durepair device" is a physical product designed and validated through engineering and biological testing, not trained on data.

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

Not applicable. As established in point 8, there is no "training set" for this device.

Summary

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

November 2, 2016

Medtronic Neurosurgery Manas Lele Senior Regulatory Affairs Specialist 125 Cremona Drive Goleta, California 93117

Re: K161370

Trade/Device Name: Durepair Dura Regeneration Matrix Regulation Number: 21 CFR 882.5910 Regulation Name: Dura Substitute Regulatory Class: Class II Product Code: GXQ Dated: September 27, 2016 Received: September 28, 2016

Dear Mr. Lele:

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 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.

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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, Michael J. Hoffmann -A

Carlos L. Peña. PhD, MS for 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) K161370

Device Name Durepair Dura Regeneration Matrix

Indications for Use (Describe) Durepair is indicated as a dura substitute for the repair of the 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

This 510(k) summary is submitted in accordance with the requirements of 21 CFR 807.92.

510(k) Owner:	Medtronic Neurosurgery125 Cremona DriveGoleta, CA 93117-5503 USA
Contact Name:	Manas LeleSenior Regulatory Affairs SpecialistTelephone: (805) 571-8956Email: Manas.M.Lele@Medtronic.com
Date Summary Prepared:	October 31, 2016
Trade or Proprietary Name:	Durepair Dura Regeneration Matrix
Common Name:	Dura Substitute
Classification Name:	Dura Substitute(21 CFR §882. 882.5910, Product Code GXQ)
Predicate Device:	Durepair Dura Regeneration Matrix (K063117 K041000 and K052211)

Device Description:

Indications for Use:

Durepair is indicated as a dura substitute for the repair of the dura mater.

Summary of Technological Characteristics Compared to the Predicate Device:

The proposed Durepair Dura Regeneration Matrix incorporates the same basic technological characteristics as the predicate device. The manufacturing process change relative to the predicate device did not affect the device design, indications of use, material or the fundamental technology of the device.

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		Table 1 - Summary of Technological Characteristics Comparison between Predicate
	Durepair Device and Proposed Durepair Device

TechnologicalCharacteristic	Predicate Durepair Device	Proposed Durepair Device
FundamentalTechnology	Collagen implant for the repair ofthe defects in the dura mater	Same. The Fundamental Technology hasnot changed.
Sizes	Durepair is available in differentsizes1" x 1"1" x 3"2" x 2"3" x 3"4" x 5"5" x 8"	Same. The length or width sizes ortolerances have not changed
Suturability	Use of suture allowed to securedevice	Same. This characteristic has notchanged.
Material	Collagen matrix harvested fromprocessed fetal bovine materials	Same. The proposed device is madefrom the collagen matrix
Cut product to size	Durepair can be cut ot size basedon user need	Same. This characteristic has notchanged.
ManufacturingProcess (Use ofSolvents)	Use of organic solvents	No use of organic solvents. Replacementwith equivalent processing step.

Table 2 – Summary of Bench Top Testing:

The following bench testing was submitted in support of substantial equivalence.

Test	Test Method Summary for Proposed Durepair device	Results for Proposed Durepair device
Sizes	The specified length or width had a tolerance of $\pm$ 5%. Measured with digital calipers and were inspected 100%.	All samples met the acceptance criteria, demonstrating that there are no concerns regarding the physical attributes of the proposed device in comparison to the predicate device.
TensileStrength	Tensile Strength must be an average 5 MPa minimum. All skins were sampled at the two thinnest corners of each skin representing worst case.	All samples met the acceptance criteria, demonstrating that there are no concerns regarding the strength and stiffness attributes of the proposed device in comparison to the predicate device.
TensileStiffness	Tensile Stiffness must have an average 225 MPa maximum. All skins were sampled at the two thinnest corners of each skin representing worst case.	All samples met the acceptance criteria, demonstrating that there are no concerns regarding the strength and stiffness attributes of the proposed device in comparison to the predicate device.
Test	Test Method Summary forProposed Durepair device	Results for Proposed Durepair device
SutureRetentionStrength	At a pull rate of 20mm/min, 3 mmsuture bite using polypropylene 4-0suture, suture strength must be aMinimum of 5 N. Two suture retentionsamples were taken from the thinnest(weakest) areas of each skin.	All samples met the acceptance criteria,demonstrating that there are no concernsregarding the ability to maintain a sutureon the proposed device in comparison tothe predicate device.
Wet ShrinkTemperature	Wet shrink Temperature - Hydratedspecimens must be 58° - 67° C (an inprocess specification). A DifferentialScanning Colorimeter was used.Indicator that the scaffold has notbeen damaged during processing.	All samples met the acceptance criteria,demonstrating that there are no concernsregarding the ability to maintain a sutureon the proposed device in comparison tothe predicate device.
Pore Size	No visible through pores should beseen and this test helps determinethe material porosity	All samples met the acceptance criteria,demonstrating that there are no concernsregarding the physical attributes ofproposed device in comparison to thepredicate device.
Hydration Rate	Time to hydrate must be less than orequal to 3 minutes. Saline solution isused to hydrate at room temperature	All samples met the acceptance criteria,demonstrating that there are no concernsregarding the hydration rate time ofproposed device in comparison to thepredicate device.
Histology (WetEBM)	No cells or cellular/nuclear debrisevident.To demonstrate the EBM is free ofcells and cellular/nuclear debris	All samples met the acceptance criteria,demonstrating that there are no concernsregarding the contents of the proposeddevice in comparison to the predicatedevice.
Safety	Must be non-pyrogenic (Less than orequal to 2.15 EU/device)No bacterial endotoxins verified pereach production lot.	All samples met the acceptance criteria,demonstrating that there are no concernsregarding the contents of the proposeddevice in comparison to the predicatedevice.
Bioburden	No bioburden observed in the finalrinse water, 0 CFUs for each lot.Final rinse water samples collectedfor each lot.	All samples met the acceptance criteria,demonstrating that there are no concernsregarding the contents of the proposeddevice in comparison to the predicatedevice.
Test	Test Method Summary	Result
Calcification	No calcification. Samples implanted intoweanling rats for 4 weeks, explants wereexamined grossly and microscopically.Samples were tested for potential for calcification.	Pass.No calcification waspresent in thesamples.
Cytotoxicity	Per ISO 10993-5Test item considered non-cytotoxic if none ofcultures exposed to test item show greater thanmild reactivity (grade 2)Lots tested for biological reactivity by exposingmouse fibroblasts to a MEM elution of product.	Pass.None of the culturesshowed greater thangrade 2 of reactivity.
Skin Sensitization Study(Saline & Cottonseed OilExtraction)	Per ISO 10993-10No significant dermal contact sensitization.Extract of EBM was tested for allergenic potentialvia the guinea pig maximization test	Pass.All test animalsscored a 0 and hadno significant dermalcontact sensitization.
Irritation Study,Intracutaneous Injection(Saline & Cottonseed OilExtraction)	Per ISO 10993-10Mean reaction scores for the test articles must be< 1.0Extract of EBM was evaluated for its potential toproduce irritation after Intracutaneous injection inrabbits	Pass.Mean reactionscores for the testarticles were <1.0.
Acute Systemic Toxicity,Systemic Injection(Saline & Cottonseed OilExtraction)	Per ISO 10993-11No evidence of mortality or acute systemictoxicity.Extract of EBM was evaluated for its potential tocause acute toxicity after intravenous and intraperitoneal injection in mice.	Pass.No test or controlanimals showedsigns of toxicity.
Hemolysis, Rabbit Blood	Per ISO 10993-4Corrected % hemolytic index for direct andindirect contact must be < 5%.The samples were evaluated for hemolytic activityon rabbit blood via both direct and indirectcontact.	Pass.Corrected %hemolytic index fordirect and indirectcontact was < 5%.
IntramuscularImplantation Study (4weeks & 12 weeks)	Per ISO 10993-6Must be non-reactive.Samples evaluated for local tissue responses andthe potential to induce local toxic effects afterimplantation in a rat intramuscular model	Pass.Noreactionwasseen in the samples.
Genotoxicity, AmesReverse Mutation Assay	Per ISO 10993-3No 2X, or greater, increase in the mean number ofrevertants compared to the negative control.Extracts of EBM were evaluated for potentialmutagenicity in certain bacteria via a change in theirdependence for histidine or tryptophan.	Pass.None of the testarticle extractsinduced a significantincrease in numberofrevertantsas
Test	Test Method Summary	Result
		compared to the negative control.

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In all cases, the results of bench testing met applicable pre-established acceptance criteria and raised no concerns regarding safety and effectiveness relative to the predicate device. Therefore, the bench testing summarized above supports the substantial equivalence of Durepair® Dura Regeneration Matrix and the predicate device.

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Biocompatibility Testing:

Table 3 – Summary of Biocompatibility Testing:

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In all cases, Durepair® passed biocompatibility testing, demonstrating that the Durepair chemical change process does not raise any biocompatibility concerns relative to the predicate device. Therefore, the biocompatibility testing summarized above supports the substantial equivalence of Durepair and the predicate device.

Conclusion:

Based on the indications of use, design and technology similarities, performance testing including bench and biocompatibility testing performed on the proposed device, it can be concluded that the proposed Durepair® Dura Regeneration Matrix is substantially equivalent to the currently marketed Durepair® cleared devices under K063117, K052211 and K041000.

Regulation Number and Section

§ 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).