Augmentation or reconstructive treatment of the alveolar ridge.
Filling of infrabony periodontal defects.
Filling of defects after root resection, apicoectomy, and cystectomy.
Filling of extraction sockets to enhance preservation of the alveolar ridge.
Elevation of the maxillary sinus floor.
Filling of periodontal defects in conjunction with products intended for Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR).
Filling of peri-implant defects in conjunction with products intended for Guided Bone Regeneration (GBR).

Device Description

EquiMatrix™ is a sterile, natural, non-antigenic, porous bone mineral matrix produced by the removal of organic compounds from equine bone. Due to its natural structure EquiMatrix™ is physically and chemically comparable to the mineralized matrix of human bone. The anorganic bone matrix of EquiMatrix™ has a macro and microporous structure similar to human bone. The formation and in-growth of new bone at the implantation site of EquiMatrix™ is favored due to its trabecular architecture, interconnecting macro and micro pores, and its natural consistency. It is supplied as cancellous (spongiosa) or cortical granules in a single use container, packaged in a secondary thermoform blister, and sterilized by v-irradiation.

AI/ML Overview

The provided document is a 510(k) summary for the EquiMatrix™ Natural Bone Mineral Matrix. It describes the device, its intended use, and argues for its substantial equivalence to a predicate device, Bio-Oss®.

Here's an analysis of the provided text in relation to your request about acceptance criteria and a study proving device conformance:

The document does not describe an AI/ML device. It is a regulatory submission for a medical device (bone grafting material) that is a physical product, not a software algorithm. Therefore, many of your specific questions related to AI/ML device performance (like sample sizes for test sets, data provenance, ground truth establishment by experts, MRMC studies, standalone performance, training sets) are not applicable to this document.

However, I can extract information related to the device's "performance" and "acceptance criteria" as understood in the context of this biological material.

1. Table of Acceptance Criteria and Reported Device Performance

For this type of device, "acceptance criteria" are typically demonstrating equivalence to a recognized standard or predicate device in terms of material properties, biocompatibility, and intended biological function (e.g., bone formation). The document argues for substantial equivalence to Bio-Oss®.

Item	Acceptance Criteria (based on equivalence to predicate/standards)	Reported Device Performance (EquiMatrix™)
Intended Use	Used as an adjunctive therapy in restoring bony defects (matching predicate)	Used as an adjunctive therapy in restoring bony defects. Applications include augmentation/reconstruction of alveolar ridge, filling various bone defects (periodontal, post-resection/cystectomy, extraction sockets), maxillary sinus floor elevation, and use with GTR/GBR products.
Target Population	Human oral, periodontal (matching predicate)	Human oral, periodontal
Dosage Form	Granules contained in single use container (matching predicate)	Granules contained in single use container
Granule Sizes	0.25 mm to 1.0 mm or 1.0 mm to 2.0 mm granules (matching predicate)	0.2 mm to 1.0 mm or 1.0 mm to 2.0 mm granules (Slight difference in lower bound of smaller size, but deemed equivalent)
Material	Anorganic naturally derived osteoconductive hydroxyapatite bone mineral (matching predicate)	Anorganic naturally derived osteoconductive hydroxyapatite bone mineral (from equine bone)
Source Bone	Biological source for anorganic bone mineral. Not explicitly an "acceptance criteria" beyond general material characteristics from xenograft, but the difference from predicate (equine vs. bovine) is a key point of comparison.	Equine bone
Physical Morphology	Trabecular, interconnecting macro and micro pores (matching predicate)	Trabecular, interconnecting macro and micro pores (similar to human bone)
Biocompatibility	Biocompatibility as per ISO 10993 and FDA's "Class II Special Controls Guidance Document: Dental Bone Grafting Devices" (matching predicate's inherent biocompatibility)	Biocompatible, demonstrated by: Genotoxicity, Intracutaneous reactivity, Maximization and sensitization, Pyrogen, Acute systemic injection, Cytotoxicity, Implantation, Preclinical safety and efficacy testing, Clinical case series. Confirmed product safety.
Performance (Bone Formation)	Osteoconductive and supports bone formation (matching predicate's known function)	Supports bone formation; "formation and in-growth of new bone at the implantation site of EquiMatrix™ is favored due to its trabecular architecture, interconnecting macro and micro pores, and its natural consistency." Animal studies showed both products (EquiMatrix™ and Bio-Oss®) grew new bone and resorbed at similar rates. Clinical case series resulted in "defect healing and formation of new bone of sufficient quality to obtain dental implant placement."
Chemical Composition	Similar to predicate's chemical composition (based on chemical analyses, XRD, FT-IR, and ICP analysis)	Similar to Bio-Oss® based on chemical analyses, XRD, FT-IR, and ICP analysis. Organic material removed, product specifications established to limit protein content.
Sterilization Process	Sterile by Gamma irradiation (matching predicate)	Sterile by Gamma irradiation (achieving SAL 1 x 10⁻⁶)
Chemical Safety	Biocompatible (matching predicate)	Biocompatible
Pyrogen Free	Yes (matching predicate)	Yes
Shelf Life	Acceptable shelf-life demonstrated. Predicate's shelf life is "determined by manufacturer," so the criteria is to have a valid, determined shelf life.	3 years

Since this is a non-AI/ML device, the following points are not applicable or cannot be extracted from the document:

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Not applicable as this is not an AI/ML device. The document mentions "several animal studies" and a "clinical case series" but does not provide sample sizes or data provenance details for these studies.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable as this is not an AI/ML device. Ground truth, in a clinical sense for this device, would be histological analysis of bone growth, clinical outcomes (implant placement success), and assessment of defect healing, typically done by attending clinicians or pathologists, but not "experts establishing ground truth for a test set" in the AI/ML context.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable as this is not an AI/ML device.

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 as this is not an AI/ML device.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Not applicable as this is not an AI/ML device.

7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

For the biological performance of the device (bone formation), the document implies:
- Histological assessment: Implied by "formation and in-growth of new bone," likely from the animal studies.
- Clinical outcomes data: Mention of "defect healing and formation of new bone of sufficient quality to obtain dental implant placement" from the "clinical case series" suggests clinical assessment of surgical sites and successful subsequent treatment.
- Physico-chemical characterization: Ground truth for material properties (composition, morphology) is established through analytical techniques like XRD, FT-IR, ICP analysis.

8. The sample size for the training set

Not applicable as this is not an AI/ML device.

9. How the ground truth for the training set was established

Not applicable as this is not an AI/ML device.

Summary

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111

510(k) Summary 2.0

K111816

Sponsor/Applicant

Luitpold Pharmaceuticals, Inc. One Luitpold Drive, PO Box 9001 Shirley, NY 11967 Phone: 610.650.4200 Fax: 610.650.0114 Contact: Marsha E. Simon

SEP 2 9 2011

Date Prepared: June 23, 2011

Device Name and Identification

Proprietary Name:

EquiMatrix™

Common/Usual Name:

Natural Bone Mineral Matrix Anorganic Equine Bone Grafting Material

Classification Name:

Bone Grafting Material Animal Source Dental Bone Grafting Material

Predicate Device

Bio-Oss® natural bone grafting material (K871773, K952617, K970321. K033815) Manufactured by: Geistlich Pharma AG Bahnhofstrasse 40 CH-6110 Wolhusen Switzerland

Device Category/Class

Class II Device Class: Regulation Number: 21 C.F.R. 872.3930 Product Code: NPM

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K111816

Intended Use

EQUIMATRIX™ cancellous and cortical granules are recommended for:

Augmentation or reconstructive treatment of the alveolar ridge. -
Filling of infrabony periodontal defects. 1
Filling of defects after root resection, apicoectomy, and cystectomy. -
Filling of extraction sockets to enhance preservation of the alveolar ridge. -
Elevation of the maxillary sinus floor. -
Filling of periodontal defects in conjunction with products intended for - Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR).
Filling of peri-implant defects in conjunction with products intended for ー Guided Bone Regeneration (GBR).

Device Description

Technological Aspects of Particulate Bone Grafting

Particulate bone grafts (cancellous and cortical) are widely used in dentistry for the treatment of periodontal bone defects, prevention of alveolar resorption following tooth extraction, and to augment deficient and atrophic sites prior to implant placement.

Although autogenous tissue has been traditionally regarded as the gold standard for bone regeneration, it has the disadvantage of limited availability, increased patient morbidity, and irregular resorptive patterns. Therefore, other sources of graft material including allogenic, alloplastic, and xenogenic particles have been developed and studied as an osteoconductive matrix for new bone formation.

Xenoarafts of bovine origin have proven to be especially useful for guided bone regeneration in stabilizing the blot clot, promoting revascularization and maintaining space during wound healing. There is also an inherent advantage in these xenografts for sinus augmentation and in the aesthetic zone as a foundation for implant and dental reconstruction due to the slower resorption rate.

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K///816

Equimatrix is a particulate natural bone mineral derived from horses which is proposed as an alternative xenograff material for use where dental bone grafting is required for treatment of periodontal defects and implant site development.

Basis for Substantial Equivalence

EquiMatrix™ and Bio-Oss® have a similar physical and chemical structure. Both are porous, biocompatible bone grafts that facilitate the formation and mineralization of new bone by the osteoblast. The primary difference between the two products is the source bone: EquiMatrix™ is manufactured from equine (horse) bones, while Bio-Oss® is manufactured from bovine (cows) source material.

The following table summarizes the basis for the Sponsor's substantial equivalence determination:

Item	EquiMatrix™	Bio-Oss®
Intended use	Used as an adjunctive therapy in restoring bony defects	Used as an adjunctive therapy in restoring bony defects
Target population	Human oral, periodontal	Human oral, periodontal
Dosage form	Granules contained in single use container	Granules contained in single use container
Granule sizes	0.2 mm to 1.0 mm or1.0 mm to 2.0 mmgranules	0.25 mm to 1.0 mm or1.0 mm to 2.0 mmgranules
Material	Anorganic naturallyderived osteoconductivehydroxyapatite bonemineral	Anorganic naturallyderived osteoconductivehydroxyapatite bonemineral
Table 1 (continued)Item	EquiMatrix™	Bio-Oss®
Source bone	Equine bone	Bovine bone
Physical Morphology	Trabecular,interconnecting macroand micro pores	Trabecular,interconnecting macroand micro pores
Biocompatibility	Biocompatible, asdemonstrated by:- Genotoxicitytesting- Intracutaneousreactivity testing- Maximization andsensitizationtesting- Pyrogen testing- Acute systemicinjection testing- Cytotoxicitytesting- Implantationtesting- Preclinical safetyand efficacytesting- Clinical caseseries	Biocompatible (asdemonstrated inpublished literature)
Performance	Bone formation	Bone formation
Compatibility w/otherdevices	Can be used with GTRmembrane	Can be used with GTRmembrane
Sterilization Process	Sterile by Gammairradiation	Sterile by Gammairradiation
Chemical Composition	Similar to Bio-Oss®based on chemicalanalyses, XRD, FT-IR,and ICP analysis	Similar to EquiMatrix™based on chemicalanalyses, XRD, FT-IR,and ICP analysis
Chemical safety	Biocompatible	Biocompatible
Anatomical sites	Oral, Periodontal	Oral, Periodontal
Pyrogen Free	Yes	Yes
Shelf life	3 years	Determined byManufacturer

Substantial Equivalence Comparison Table 1

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K///8/6

Brief Summary of Data Submitted in Support of Effectiveness

The Sponsor evaluated the performance characteristics of EquiMatrix™ and Bio-Oss® with a thorough chemical and physical characterization. The physical and chemical characteristics of the products were found to be comparable. Further,

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K///8/6

in several animal studies, both products were found to grow new bone and be subsequently resorbed at similar rates. Finally, in a clinical case series, use of EquiMatrix™ resulted in defect healing and formation of new bone of sufficient quality to obtain dental implant placement.

Brief Summary of Data Submitted in Support of Safety

EquiMatrix™ was the subject of the full range of biocompatibility tests recommended in the FDA's "Class II Special Controls Guidance Document: Dental Bone Grafting Devices" and in accordance with ISO 10993. Test results confirmed product safety. Organic material has been removed from the product, and product specifications have been established to limit protein content. Further, the product is sterilized to achieve a sterility assurance level SAL 1 x 10°.

Based on the information presented herein, it has been demonstrated that EquiMatrix™ is substantially equivalent to Bio-Oss®, and safe and effective for the proposed indications for use.

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Image /page/5/Picture/1 description: The image shows a logo for the Department of Health & Human Services. The logo features a stylized abstract symbol resembling three curved lines or waves, positioned to the right. To the left of the symbol, the text "DEPARTMENT OF HEALTH & HUM" is arranged vertically along the edge of the logo, followed by "SERVICES" below.

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

Ms. Marsha Simon Manager, Regulatory Affairs Luitpold Pharmaceuticals, Incorporated One Luitpold Drive P.O. Box 9001 Shirley, New York 11967

SEP 2 9 2011

Re: K111816

Trade/Device Name: EquiMatrix™ Natural Bone Mineral Matrix Regulation Number: 21 CFR 872.3930 Regulation Name: Bone Grafting Material Regulatory Class: II Product Code: NPM Dated: September 23, 2011 Received: September 26, 2011

Dear Ms. Simon:

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.

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Page 2 -- Ms. Simon

Enclosure .

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 device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in 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 go to 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 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.htmlfor 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.

Zh for

Anthony D. Watson, B.S., M.S., M.B.A. Director Division of Anesthesiology, General Hospital, Infection Control and Dental Devices

Office of Device Evaluation

Center for Devices and

Radiological Health

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111816

1.0 Indications for Use Statement

INDICATIONS FOR USE

510(K) Number: EquiMatrix™ Natural Bone Mineral Matrix Device Name:

INDICATIONS AND USAGE:

EQUIMATRIX™ cancellous and cortical granules are recommended for:

Augmentation or reconstructive treatment of the alveolar ridge. -
Filling of infrabony periodontal defects. -
Filling of defects after root resection, apicoectomy, and cystectomy. -
Filling of extraction sockets to enhance preservation of the alveolar ridge. -
Elevation of the maxillary sinus floor. -
Filling of periodontal defects in conjunction with products intended for Guided ﺖ Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR).
Filling of peri-implant defects in conjunction with products intended for Guided -Bone Regeneration (GBR).

Prescription Use _ V AND/OR (Part 21 CFR 801 Subpart D)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Melle

(Division Sign-Off) Division of Anesthesiology, General Hospital Infection Control, Dental Devices

510(k) Number: K111816

Regulation Number and Section

§ 872.3930 Bone grafting material.

(a)
Identification. Bone grafting material is a material such as hydroxyapatite, tricalcium phosphate, polylactic and polyglycolic acids, or collagen, that is intended to fill, augment, or reconstruct periodontal or bony defects of the oral and maxillofacial region.(b)
Classification. (1) Class II (special controls) for bone grafting materials that do not contain a drug that is a therapeutic biologic. The special control is FDA's “Class II Special Controls Guidance Document: Dental Bone Grafting Material Devices.” (See § 872.1(e) for the availability of this guidance document.)(2) Class III (premarket approval) for bone grafting materials that contain a drug that is a therapeutic biologic. Bone grafting materials that contain a drug that is a therapeutic biologic, such as biological response modifiers, require premarket approval.
(c)
Date premarket approval application (PMA) or notice of product development protocol (PDP) is required. Devices described in paragraph (b)(2) of this section shall have an approved PMA or a declared completed PDP in effect before being placed in commercial distribution.