Lyoplant Onlay is a dura substitute implant made of pure collagen that is obtained from bovine pericardium and bovine split hide. Lyoplant Onlay can be laid on the defect, or sutured depending upon surgeon preference. After implantation, it is gradually broken down enzymatically and is replaced by the body's own connective tissue. The appropriate size implant is selected depending on the area of application and is cut to size depending on the size of the defect. Lyoplant Onlay is supplied sterile and packaged as a single piece.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the Lyoplant® Onlay device:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly list quantitative acceptance criteria in a dedicated table format with corresponding performance results. Instead, it states that "Physical, mechanical, and biocompatibility testing have been performed on Lyoplant Onlay in accordance with the FDA guidance for industry for Dura Substitute Devices and has demonstrated the performance of Lyoplant Onlay as a dura substitute."

The tests conducted are listed as:

Test Category	Specific Tests Conducted	Reported Performance/Outcome
Physical/Mechanical	Device Thickness, Tensile Strength, Suture Retention Strength, Burst Strength, Shrink Temperature Range, Surface Structure, Delamination, Chemical Characterization	The document attests that these tests "demonstrated the performance of Lyoplant Onlay as a dura substitute" and that the device possesses "adequate tear resistance and handling properties, impermeability to CSF."
Biocompatibility	Cytotoxicity, Maximization Sensation Study, Intracutaneous Study, Systematic Toxicity, Genotoxicity, Hemolysis, Muscle Implantation (all in accordance with ISO 10993-1)	The submission implies that these tests were passed, as it states the device has "satisfactory biocompatibility."
Animal Study (In Vivo)	Safety and Efficacy of Lyoplant® Onlay as a dura onlay graft in an in vivo model (comparing to Suturable DuraGen™ and autologous periosteum)	- Handling: Superior handling of Lyoplant® Onlay and Suturable DuraGen™ over periosteum.- Adhesion/CSF Tightness: Trend for better adhesion to dura and CSF tightness for Lyoplant® Onlay. Periosteum had highest intraoperative CSF tightness (when sutured).- Duraplasty Time: Significantly lower for Lyoplant® Onlay (2.8±0.8 min) compared to periosteum (14.4±2.7 min).- Tissue Integration: Fibroblast infiltration observed after 1 month for all devices; all devices completely integrated after 6 months.- Adhesions (Graft-Cortex): More adhesions with Suturable DuraGen™ compared to Lyoplant® Onlay and periosteum. No relevant adhesions between leptomeninges and Lyoplant® Onlay.- Lymphocytic Reaction: Comparable lymphocytic reaction of the brain for all devices. Lyoplant® Onlay and Suturable DuraGen™ showed a trend for enhanced lymphocytic reaction of brain parenchyma compared to periosteum.- Implant Rejection: Not observed in any animals.- Mortality: Several deaths in periosteum (n=3) and Suturable DuraGen™ (n=4) cohorts; not reported for Lyoplant® Onlay.

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

Animal Study: Thirty-four (34) pigs were used for the in vivo animal study.
Data Provenance: The animal study was conducted as an in vivo model. The country of origin for the data is not explicitly stated, but the submission is to the US FDA by a US-based company (Aesculap®, Inc. in Center Valley, PA). This suggests the testing was likely overseen by or conducted for the US entity. The data is prospective for this animal study. For the physical, mechanical, and biocompatibility tests, these are typically conducted in a laboratory setting.

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

Animal Study: The document does not specify the number or qualifications of experts involved in establishing the "ground truth" for the animal study. The assessment involved "gross and histologic assessment" but does not detail who performed these or their certifications (e.g., veterinary pathologists).

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the assessment of the animal study results.

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

No MRMC comparative effectiveness study was done. The study described is an animal study comparing different dura substitute materials, not a human reader study with or without AI assistance.

6. Standalone (i.e., algorithm only without human-in-the-loop performance) Study

Not applicable. This device is a physical dura substitute implant, not an algorithm or AI-based diagnostic tool. The performance studies are clinical (animal model) and laboratory-based, assessing material properties.

7. Type of Ground Truth Used

Physical/Mechanical Tests: The ground truth for these tests would be the established scientific and engineering principles and the measurement standards for material properties (e.g., ISO standards for tensile strength, burst strength, etc.).
Biocompatibility Tests: The ground truth is defined by the toxicological and biological response criteria outlined in ISO 10993-1 for biological evaluation of medical devices.
Animal Study: The ground truth was established through direct observation (gross assessment) and microscopic examination (histologic assessment) of tissue responses and material integration in the animal model at predefined time points (1 and 6 months post-implantation). This can be considered a form of "pathology" or "biological outcomes" data in an animal model.

8. Sample Size for the Training Set

Not applicable. This device is a physical product, not an AI or algorithm that requires 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.

Summary

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K122791 Page 1 of 3

C. 510(K) SUMMARY As required by 21 CFR 807.92

JUN 0-4 2013

LYOPLANT® ONLAY

September 10, 2012

Aesculap®, Inc. COMPANY: 3773 Corporate Parkway Center Valley, PA 18034 Registration No .: 2916714

CONTACT: Denise R. Adams, Requlatory Affairs Specialist 610-984-9076 (phone) 610-791-6882 (fax) denise.adams@aesculap.com (email)

TRADE NAME:	Lyoplant® Onlay
COMMON NAME:	Dura Substitute
REGULATION:	Dura Substitute
CLASS:	II
PRODUCT CODE:	GXQ
REGULATION:	882.5910
REVIEW PANEL:	Neurology

INTENDED USE

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

DEVICE DESCRIPTION

Lyoplant Onlay is a dura substitute implant made of pure collagen that is obtained from bovine pericardium and bovine split hide.

Lyoplant Onlay can be laid on the defect, or sutured depending upon surgeon preference. After implantation, it is gradually broken down enzymatically and is replaced by the body's own connective tissue. The appropriate size implant is selected depending on the area of application and is cut to size depending on the size of the defect. Lyoplant Onlay is supplied sterile and packaged as a single piece.

TECHNOLOGICAL CHARACTERISTICS

Lyoplant Onlay is available as single use, sterile, flexible sheets of pure collagen with adequate tear resistance and handling properties, impermeability to CSF, and satisfactory biocompatibility, thus fulfilling the requirements of a dura substitute as described in FDA's quidance document for Dura Substitute Devices.

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K122791

Page 2 of 3

PERFORMANCE DATA

Physical, mechanical, and biocompatibility testing have been performed on Lyoplant Onlay in accordance with the FDA quidance for industry for Dura Substitute Devices and has demonstrated the performance of Lyoplant Onlay as a dura substitute.

The following tests were conducted as recommended in the FDA quidance on Dura Substitute Devices:

Device Thickness .
Tensile Strength .
Suture Retention Strenath .
. Burst Strength
Shrink Temperature Range .
Surface Structure .
Delamination .
Chemical Characterization .

The following biocompatibility testing was conducted in accordance with ISO 10993-1:

Cytotoxicity .
. Maximization Sensation Study
. Intracutaneous Study
Systematic Toxicity .
Genotoxicity .
. Hemolysis
Muscle Implantation .

Additionally, an animal study was conducted using thirty-four (34) pigs. The study was designed to investigate the safety and efficacy of Lyoplant® Onlay as a dura onlay graft in an in vivo model. Suturable DuraGen" and autologous periosteum were used as control materials. Animals were sacrificed at one (1) month and six (6) months at which time gross and histologic assessment was made. Results of the study demonstrate superior handling of Lvoplant® Onlay and Suturable DuraGen™ over periosteum with a trend for better adhesion to dura and CSF tightness for Lyoplant® Onlay. Periosteum, which was sutured, had the highest intraoperative CSF tightness. Duraplasty time with periosteum was significantly higher (14.4±2.7 min) compared with Lyoplant® Onlay (2.8±0.8 min) or Suturable DuraGen™ (3.0±0.5 min). Tissue integration by fibroblast infiltration was observed after one (1) month for all devices. More adhesions between graft and cortex were observed with Suturable DuraGen ™ compared with Lyoplant® Onlay and periosteum. No relevant adhesions between leptomeninges and Lyoplant® Onlay were observed and all devices showed comparable lymphocytic reaction of the brain. All devices were completely integrated after six (6) months. Lyoplant® Onlay and Suturable DuraGen™ showed a trend for an enhanced lymphocytic reaction of the brain parenchyma compared with periosteum. Implant rejection was not observed in any animals but several deaths occurred overall in the periosteum (n=3) and Suturable DuraGen™(n=4) cohorts.

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K122791

Results of in vitro, in vivo, and biocompatibility testing demonstrate that Lyoplant Onlay performs in accordance with its specifications and is substantially equivalent in safety and effectiveness to the predicate devices Lyoplant , Suturable DuraGen, and Durepair,

SUBSTANTIAL EQUIVALENCE

Lyoplant Onlay, Lyoplant, Suturable DuraGen, and Durepair have similar technological characteristics. These devices are available as single use, sterile, flexible sheets of pure collagen with adequate tear resistance and handling properties, impermeability to CSF, and satisfactory biocompatibility, thus fulfilling the requirements of a dura substitute.

The device modifications described in this premarket notification are substantially equivalent to the predicate device Lyoplant Dura Substitute cleared via K970851. Suturable DuraGen cleared via K043427, and Durepair cleared via K041000. Anv technological differences between Lyoplant Onlay and the predicate devices do not raise new types of safety or effectiveness issues.

	Lyoplant Onlay(subject device)	Lyoplant K970891Aesculap	Suturable DuraGenK043247 IntegraLifeSciences	Durepair K041000Medtronic
Indicationsfor Use	Lyoplant Onlay isindicated as a durasubstitute for therepair of the duramater.	Intended as a duramater substitute inneurologicalprocedures for softtissue reconstructionof damaged, impaired,or missing tissue.	Indicated as a durasubstitute for the repairdura mater	Durepair® isindicated as a durasubstitute for therepair of the duramater.
Contra-indications	• Infected areas• Open cranial trauma• Open spina bifida• As a replacement formechanically stressedconnective tissuestructures• As a substitute forparts in the arterialsystem or the cardiacwall• If there are knownallergies to proteins ofbovine origin	• Infected areas• Open cranial trauma• Open spina bifida• As a replacement formechanically stressedconnective tissuestructures• As a substitute forparts in the arterialsystem or the cardiacwall	• For patients with aknown history ofhypersensitivity tobovine derived materials• Should be used withcaution in infectedregions	• Durepair is notdesigned, sold, orintended for useexcept as indicated.• Durepair should notused for patientswith a known historyof hypersensitivity tocollagen products.• Durepair should beused with caution inregions where aninfection exists.
Type ofCollagen	bovine pericardiumand bovine split hide	bovine pericardium	bovine Achilles tendon	bovine skin
Application	Onlay or suture	Suture	Onlay or suture	Onlay or suture
Sterilization	EtO	EtO	EtO	EtO

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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name encircling a symbol. The symbol is a stylized representation of an eagle with outstretched wings, with three wavy lines below it, possibly representing water or waves.

June 4, 2013

Public Health Service

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

Aesculap, Inc. % Ms. Denise R. Adams Regulatory Affairs Specialist 3773 Corporate Parkway Center Valley, PA 18034

Re: K122791

Trade/Device Name: Lyoplant® Onlay Regulation Number: 21 CFR 882.5910 Regulation Name: Dura Substitute Regulatory Class: Class II Product Code: GXQ Dated: April 29, 2013 Received: April 30, 2013

Dear Ms. Adams

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

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Page 2 - Ms. Denise R. Adams

device-related 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 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 vours,

Kesia Y Alexander -S

for Victor Krauthamer, Ph.D. Acting Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Genter-for-Devices-and-Radiological-Health

Enclosure

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Page 1 of 1

A. INDICATIONS FOR USE STATEMENT

510(k) Number (if known): _ K122791

Device Name: Lyoplant® Onlay

Indication for Use:

Lyoplant® Onlay is indicated as a dura substitute for the repair of the dura mater.

Prescription Use X Over-the-Counter Use or (Per 21 CFR 801.109)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

Tieuvi Hī 2013.05.22 22

(Division Sign Off) Division of Neurological and Physical Medicine Devices (DNPMD) 510 (k) Number K122791

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).