SyntheCel® Dura Replacement Devices are intended for use as a dura replacement for the repair of dura mater. SyntheCel® Dura Onlay is indicated for use in adults for the repair of dural defects and it can be placed without sutures. SyntheCel® Dura Substitute is indicated for use in adults for the repair of dural defects and it can be sutured into place.

Device Description

SyntheCel® Dura Replacement Devices (Onlay and Substitute) are composed of biosynthesized cellulose and water with a unique construction of non-woven, interconnected cellulose fibers. SyntheCel® Dura Replacement Devices function as a mechanical layer which protects and repairs the dural defect while preventing further CSF leakage. SyntheCel® Dura Replacement Devices are immunologically inert and have demonstrated minimal foreign body response. They are non-resorbable.

AI/ML Overview

The provided text describes the SyntheCel® Dura Replacement Devices and the studies performed to demonstrate their safety and effectiveness for FDA clearance.

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

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Primary Efficacy Endpoint)	Reported Device Performance
Absence of CSF fistula (drainage from wound or sinus) and pseudomeningocele within 6 months post-operatively, confirmed by radiographic evaluation and physical examination of the surgical site.	The results of overall success analyses indicate that the SyntheCel® is non-inferior to the dura replacement control group.
Non-Clinical Acceptance Criteria	Reported Device Performance
Tensile strength comparable to predicates	SyntheCel® Dura Replacement Device performance was found to be comparable in tensile strength.
Burst strength comparable to predicates	SyntheCel® Dura Replacement Device performance was found to be comparable in burst strength.
Suture pull-out strength comparable to predicates	SyntheCel® Dura Replacement Device performance was found to be comparable in suture pull-out strength.
No meningitis, CSF leakage, infection, hydrocephalus, device vascularization, nor significant hemorrhage in animal study.	Results noted at necropsy show no meningitis, CSF leakage, evidence of infection, hydrocephalus, device vascularization, nor significant hemorrhage in any of the animals regardless of the implant type.
No evidence of a toxic leachable or local adverse effect in animal study.	SyntheCel® Dura Replacement Devices showed no evidence of a toxic leachable or local adverse effect.
Non-irritating, non-sensitizing, non-mutagenic, non-mutagenic, non-cytotoxic, non-hemolytic, and non-pyrogenic (Biocompatibility).	Demonstrated that the material is non-irritating, non-sensitizing, non-mutagenic, non-cytotoxic, non-hemolytic, and non-pyrogenic.
Pyrogenicity < 0.06 EU/ml.	Pyrogenicity was evaluated using the Limulus Amebocyte Lysate (LAL) test and found to be less than 0.06 EU/ml.

2. Sample Size Used for the Test Set and Data Provenance

Clinical Study:
- Total Patients Enrolled: 99
- Test Set (Investigational SyntheCel® group): 62 patients
- Control Group: 37 patients
- Data Provenance: Not explicitly stated, but clinical studies for FDA submission are generally multi-site, and often international, though specific countries aren't mentioned. The study was prospective, with patients randomized and treated at 8 clinical sites.
Non-Clinical (Mechanical Testing):
- Sample Size: "samples" of SyntheCel® Dura Replacement Devices and predicates (DuraGen and Dura-Guard) were used. Specific numbers are not provided.
- Data Provenance: Not specified, likely internal lab testing.
Animal Studies (Rabbit Durotomy Implant Studies):
- Sample Size: Not explicitly stated, but "any of the animals" implies a group of animals were studied. One study was conducted "following GLPs" (Good Laboratory Practices).
- Data Provenance: Not specified, but animal studies are typically conducted by contract research organizations or internal labs.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

Clinical Study: The text mentions "physical examination of surgical site" and "radiographic evaluation," which implies assessment by medical professionals. However, the exact number of experts (e.g., surgeons, radiologists) and their specific qualifications used to establish the "ground truth" (i.e., whether CSF fistula or pseudomeningocele was present) are not explicitly stated.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method (e.g., 2+1, 3+1, none) for the clinical outcomes (CSF fistula, pseudomeningocele) in the test set.

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

No, an MRMC comparative effectiveness study was not done. The clinical study was a direct comparison of the SyntheCel® device to a control group of other dura replacement products, evaluating patient outcomes. It was not a study assessing how human readers (e.g., radiologists) improve with or without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

No. This device is a surgical implant, not an algorithm or AI system. Therefore, standalone algorithm performance is not applicable. The studies evaluated the physical device's performance in humans and animals.

7. Type of Ground Truth Used

Clinical Study: The ground truth for the clinical study was based on clinical outcomes data obtained through "radiographic evaluation and physical examination of surgical site" at 6 months post-operatively.
Mechanical Testing: The ground truth was based on physical measurements of tensile strength, burst strength, and suture pull-out strength using standardized test methods.
Animal Studies: The ground truth was established through necropsy findings and histological/toxicological evaluations in animal models.
Biocompatibility: The ground truth was based on laboratory test results from standardized ISO 10993 tests and LAL test for pyrogenicity.

8. Sample Size for the Training Set

Not applicable. This device is a medical implant, not an AI or machine learning model that requires a training set. The studies described are for regulatory clearance of the physical device.

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

Not applicable, as there is no training set for this type of device.

Summary

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K113071

JAN - 9 2012

1.0 SUMMARY OF INFORMATION REGARDING SAFETY AND EFFECTIVENESS [510(k) Summary] per the requirements 21 CFR 807.92

Page I of 3 Date Prepared January 03, 2012 Submitter SYNTHES 1301 Goshen Parkway West Chester, PA 19380 United States of America Contact Andrea M. Tasker tasker.andrea@synthes.com phone: (610) 719-6920 Trade Name SyntheCel® Dura Replacement Devices, SyntheCel® Dura Onlay, SyntheCel® Dura Substitute Common Name Dura Replacement Device Classification Dura Substitute Name Classification 21 CFR 882.5910 Device Class I I Review Panel Neurology Product Code(s) GXQ Predicate Devices Bio-Vascular's Dura-Guard (K950956, K973706,K982282) Integra Lifescience's DuraGen (K982180) Gore - Preclude MVP (K021477) SyntheCel® Dura Replacement Devices (Onlay and Substitute) are Device Description composed of biosynthesized cellulose and water with a unique construction of non-woven, interconnected cellulose fibers. SyntheCel® Dura Replacement Devices function as a mechanical layer which protects and repairs the dural defect while preventing further CSF leakage. SyntheCel® Dura Replacement Devices are immunologically inert and have demonstrated minimal foreign body response. They are non-resorbable. Intended Use SyntheCel® Dura Replacement Devices are intended for use as a dura replacement for the repair of dura mater. SyntheCel® Dura Onlay is indicated for use in adults for the repair of dural defects and it can be placed without sutures. SyntheCel® Dura Substitute is indicated for use in adults for the repair of dural defects and it can be sutured into place.

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K113071

510(k) Summary (continued)

TechnologicalCharacteristics	The SyntheCel® Dura Replacement Devices are similar to the threepredicate devices (Bio-Vascular-Dura-Guard, Integra Lifesciences-DuraGen, and Gore-Preclude MVP) in terms of intended use. All threeare intended for dura replacement for the repair of dura mater.The SyntheCel® Dura Replacement Devices are similar to the twopredicate devices (Bio-Vascular-Dura-Guard, Integra Lifesciences-DuraGen) in terms of physical properties (form, size, physical integrity,thickness, suturability, drapability, conformability).The SyntheCel® Dura Replacement Devices are similar to the predicatedevice (Gore-Preclude MVP) in terms of resorbability. Both are non-resorbable.
Clinical TestingData	Clinical data were collected to evaluate the safety and effectiveness ofthe SyntheCel® Dura Replacement Devices as compared to the Control.The objective of this study was to demonstrate that the SyntheCel® DuraReplacement Devices are substantially equivalent to other durareplacement products that were previously cleared for marketing byFDA. A total of 99 patients were enrolled, randomized and treated (62in the investigational SyntheCel® treatment group and 37 in the controlgroup) at 8 clinical sites.Patients were evaluated intra-operatively and immediately post-operatively (1 - 10 days) followed by evaluations at one (1) month, three(3) months and six (6) months. Complications and adverse events,device-related or not, were evaluated over the course of the clinical trial.At each evaluation time-point, the primary and secondary clinicaloutcome parameters were evaluated. Safety and effectiveness was assessed in all randomized subjects.Primary Efficacy Endpoint: The primary endpoint was based on thefindings up to and including the 6 month follow-up visit. An individualpatient's treatment was considered successful if and only if the followingcriterion was met:Success was defined as absence of CSF fistula (drainage from wound orsinus) and pseudomeningocele within 6 months post-operativelyconfirmed by radiographic evaluation and physical examination ofsurgical site.The results of overall success analyses indicate that the SyntheCel® isnon-inferior to the dura replacement control group.
Non-ClinicalTesting Data	Mechanical testing was performed for tensile strength, burst strength,and suture pull-out strength on samples of SyntheCel® DuraReplacement Devices and the predicates, DuraGen and Dura-Guard. Allsamples were prepared per respective instructions. SyntheCel® DuraReplacement Device performance was found to be comparable in tensilestrength, burst strength, and suture pull-out strength.An animal study was performed comparing the SyntheCel® DuraReplacement Devices and predicate devices in a Rabbit DurotomyImplant Study. The results noted at necropsy show no meningitis, CSFleakage, evidence of infection, hydrocephalus, device vascularization,nor significant hemorrhage in any of the animals regardless of theimplant type. Overall, the SyntheCel® Dura Substitute performed nodifferent than the other predicate dura substitute materials.An additional Rabbit Durotomy Implant Study Model was performedusing SyntheCel® Dura Replacement Devices. This study wasconducted by NAMSA following GLPs. According to the conclusion,the SyntheCel® Dura Replacement Devices showed no evidence of atoxic leachable or local adverse effect.Biocompatibility testing according to standards set forth in ISO 10993demonstrated that the material is non-irritating, non-sensitizing, non-mutagenic, non-cytotoxic, non-hemolytic, and non-pyrogenic.Pyrogenicity was evaluated using the Limulus Amebocyte Lysate (LAL)test on the final sterilized SyntheCel® device and found to be less than0.06 EU/ml (Endotoxin Units / ml) per FDA's Guidance Document forDura Substitute Devices. All SyntheCel® Dura Replacement Devicelots will be tested to ensure they are less than 0.06 EU/ml and will belabeled non-pyrogenic.
SubstantialEquivalence toPredicate Devices	Based on the information presented in this submission, which includesmechanical testing, pre-clinical testing, animal testing, and clinicaltesting, the SyntheCel® Dura Replacement Devices do not raise newquestions of safety and effectiveness. Therefore, it can be concludedthat the SyntheCel® Dura Replacement Devices are substantiallyequivalent to the predicate devices for dura replacement devices incommercial distribution for use as a dura replacement for the repair ofdura mater.

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510(k) Summary (continued)

3 Page 3

(end of summary)

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

JAN - 9 2012

Synthes c/o Ms. Andrea M. Tasker CMF Regulatory Affairs Manager, Synthes 1301 Goshen Parkway West Chester, PA 19380

Re: K113071

Trade/Device Name: SyntheCel® Dura Replacement Devices Regulation Number: 21 CFR 882.5910 Regulation Name: Dura Substitute Regulatory Class: Class II Product Code: GXO Dated: October 14, 2011 Received: October 18, 2011

Dear Ms. Tasker:

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

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CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical Of K Part 607), accimig (21 CFR 803); good manufacturing practice requirements as set do records and the overse oversion (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 n you http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part note the 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/Resourcesfor You/Industry/default.htm.

Sincerely yours,
Kesia Alexander

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Malvina B. Eydelman, M.D. Director Division of Ophthalmic, Neurological, and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

K113071 510(k) Number (if known):_

SyntheCel® Dura Replacement Devices Device Name:

Indications For Use:

Prescription Use X (Per 21 CFR 801.109)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sign-Off)

ision of Ophthalmic, Neurological and Ear,

Nose and Throat Devices

K11307 510(k) Number

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).