Augmentation or reconstructive treatment of the alveolar ridge;
Filling of 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 coniunction 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

OSSIX™ BONE is a biodegradable, osteoconductive, and biocompatible bone grafting material intended for guided tissue and bone regeneration. The OSSIX™ BONE matrix is composed of 80% synthetic crystalline non-sintered hydroxylapatite and 20% collagen, which is derived from veterinary certified pigs and is purified and cross-linked. OSSIX™ BONE is designed as a 3-D highly porous scaffold with physiological pH.

OSSIX™ BONE is packed in a double blister and an outer cardboard box and is sterilized by ethylene oxide; the shelf life of the device is 36 months.

Due to its porous and fibered microstructure, the matrix readily absorbs fluids, adheres to the surrounding tissues, and provides a scaffold that guides bone growth and regeneration. After implantation, OSSIX™ BONE undergoes gradual resorption in the body. Preclinical studies demonstrated that 50% or greater implant material remains at the 6-month time point.

OSSIX™ BONE is available in the following sizes: 0.125 CC (5x5x5 mm), 0.25 CC . (5x5x10 mm) and 0.5 CC (5x10x10 mm).

OSSIX™ BONE is for prescription use only; it is intended to be implanted by trained dentists or oral surgeons in clinics during routine dental surgical procedures on adults with periodontal and bony defects of the maxillo-facial complex.

AI/ML Overview

The document describes a 510(k) submission for OSSIX™ BONE, a dental bone grafting material. The goal is to demonstrate substantial equivalence to a predicate device, Geistlich Bio-Oss Collagen®.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly define "acceptance criteria" in a quantitative, pass/fail sense for each test. Instead, it aims to demonstrate substantial equivalence to the predicate device. The performance is reported in terms of similarity to the predicate or conformance to relevant standards.

Feature/Test	Acceptance Criteria (Implied / Demonstrated)	Reported Device Performance (OSSIX™ BONE)
Intended Use / Indications for Use	Same as predicate device (Geistlich Bio-Oss Collagen®)	Same as predicate. (Detailed in Section V)
Mode of Action	Same as predicate device (Conductive bone grafting material)	Conductive bone grafting material
Design	Similar to predicate device (Sterile, biodegradable, biocompatible, hydrophilic, moldable, trimmable, highly porous spongious matrix)	Sterile, biodegradable, biocompatible, hydrophilic, moldable, trimmable, highly porous spongious matrix
Composition & Source of Materials	Primarily composed of hydroxyapatite and collagen; difference in HA source and ratio is evaluated for performance impact.	Crystalline synthetic hydroxyapatite (80%) combined with porcine type I collagen (20%)
Porosity	Similar to predicate device (High porosity)	High porosity
Density	Similar to predicate device (2-3 g/cm³)	2-3 g/cm³
Particle Size	Difference noted, but performance not affected (predicate: 250 - 1000 μm)	1 - 10 μm
Max Load (Compression)	Similar to predicate device (About 40 N)	About 40 N
Sterility	Sterilized according to ISO 11135:2014, and packaging maintains sterility	ETO (Ethylene Oxide) sterilization, validated via ISO 11135:2014, with demonstrated packaging sterility
Resorption Profile	Similar to predicate device (Slow resorption)	Slow resorption; preclinical studies showed ≥50% implant material remains at 6 months.
Biocompatibility	Conform to FDA Guidance Use of International Standard ISO 10993-1, 2016, and ISO10993-1:2009. Must pass all specified tests for an implant device in contact with bone/tissue.	Tested for cytotoxicity, pyrogenicity, sensitization, intracutaneous reactivity, genotoxicity, implantation, systemic toxicity (acute), subchronic toxicity, chronic toxicity. (Implied 'passed' as it supports substantial equivalence)
In vitro product characterization (SEM, XRD, Chemical, FTIR, Amino Acid, Porosity/Density)	Characteristics confirm substantial equivalence to predicate; HA component conforms to ISO 13779-3:2008 and ASTM F1185-3:2014.	All tests were performed, showing similar characteristics to the predicate device, or conforming to the stated HA standards. The document states "technological differences... do not affect the product performance as was demonstrated by the biocompatibility, bench, and animal studies."
Animal Study (In vivo performance and degradation)	Perform similarly to the predicate device in an L-shape buccal mandibular defect model system in Beagle dogs. Demonstrate the ability of the manufacturing process to remove or inactivate viruses.	The subject OSSIX™ BONE and predicate device (Geistlich Bio-Oss Collagen®) performed similarly. Viral inactivation studies demonstrated the ability of the manufacturing process to remove/inactivate viruses.

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

Biocompatibility Testing: The specific number of samples for each biocompatibility test is not provided, but the final sterile device was tested.
Sterility Validation: Not specified, but validated according to ISO 11135:2014.
In vitro Product Characterization: Not specified, but involved comparisons between OSSIX™ BONE and the predicate device.
Animal Study:
- Sample Size: 19 Beagle dogs.
- Data Provenance: Prospective animal study conducted in "an L-shape buccal mandibular defect model system in Beagle dogs". (Country of origin not specified, but typically conducted in controlled laboratory settings).

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

General Note: For this type of 510(k) submission for a bone grafting material, "ground truth" often refers to objective measurements and histological findings rather than expert human interpretation in the same way it would for an AI diagnostic algorithm.
Biocompatibility: Ground truth is established by standard laboratory methods and readouts as per ISO 10993 series. No "experts" in the sense of human readers/interpreters are explicitly mentioned for establishing ground truth, rather qualified lab personnel conducting the tests.
Animal Study: The evaluation of performance and degradation in the animal study would involve veterinary pathologists or researchers specialized in animal models for bone regeneration. The number of such specialists is not stated, nor are their specific qualifications (e.g., years of experience).

4. Adjudication Method for the Test Set:

Not applicable in the context of this device and testing. The tests are primarily objective measurements (e.g., chemical analysis, physical properties, histological assessment in animal models) rather than subjective interpretation requiring adjudication among human readers.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done:

No, a multi-reader, multi-case comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging algorithms to assess how AI assistance impacts human reader performance. OSSIX™ BONE is a medical device (bone grafting material), not an AI diagnostic tool.

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

Not applicable. OSSIX™ BONE is a material, not an algorithm. The "standalone performance" observed would be its inherent biological and physical properties demonstrated through bench and animal studies.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc):

Biocompatibility Testing: Ground truth is based on standard, validated test methodologies and predetermined acceptance criteria outlined in ISO 10993, measured by analytical equipment or observed biological responses (e.g., cell viability, presence of inflammation).
In vitro Product Characterization: Ground truth is based on physical and chemical measurements (e.g., SEM images, XRD patterns, elemental analysis, FTIR spectra, amino acid concentrations, porosity, density, mechanical load) compared against the predicate or established standards.
Animal Study: Ground truth involved histological analysis, examination of tissue reaction, new bone formation, and degradation of the implant, which falls under pathology and histology interpretations by trained professionals. Outcomes data (e.g., long-term success of bone regeneration) were observed over 1, 3, and 6 months in the animal model.

8. The Sample Size for the Training Set:

Not applicable. OSSIX™ BONE is a medical device (bone grafting material), not an AI algorithm that requires a "training set" in the machine learning sense. The materials and manufacturing processes are developed based on scientific principles and extensive material characterization, not by training an algorithm on a dataset.

9. How the Ground Truth for the Training Set was Established:

Not applicable, as there is no "training set" for this type of medical device. The 'ground truth' for its development would be fundamental scientific understanding of material properties, biological responses, and established engineering principles.

Summary

{0}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with three tail feathers, representing the three levels of government: federal, state, and local. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.

Public Health Service

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

October 16, 2017

Datum Dental Ltd % Janice Hogan Partner Hogan Lovells US LLP 1835 Market St, 29th Floor Philadelphia, Pennsylvania 19103

Re: K163714

Trade/Device Name: Ossix Bone Regulation Number: 21 CFR 872.3930 Regulation Name: Bone Grafting Material Regulatory Class: Class II Product Code: NPM Dated: July 5, 2017 Received: July 5, 2017

Dear Janice Hogan:

This letter corrects our substantially equivalent letter, indications for use and the correct 510(k) Summary of July 18, 2017.

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

{1}------------------------------------------------

Page 2 - Janice Hogan

comply with all the Act's requirements. including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical 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 Parts 801 and 809), 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" (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 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,

Mary S. Runner -S

for

Tina Kiang, Ph.D. Acting Director Division of Anesthesiology, General Hospital, Respiratory, Infection Control, and Dental Devices Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page

510(k) Number (if known)

K163714

Device Name

OSSIX™ BONE

Indications for Use (Describe)

OSSIX™ BONE is intended for the following uses:

Augmentation or reconstructive treatment of the alveolar ridge:
Filling of 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 coniunction 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). .

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR 801 Subpart D)

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

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

datumdental

510(k) Summary

I. Submitter

Datum Dental Ltd. 1 Bat Sheva st., PO Box 6170 Lod 7116003 Israel Phone: 1-972-8-6705400 Fax: 1-972-8-6705429 Arie Goldlust, CEO, VP R&D Contact person:

Date prepared: July 5, 2017

II. Device

Trade name:	OSSIX™ BONE
Common name:	Dental bone grafting material
Classification name:	Bone grafting material (21 CFR 872.3930)
Regulatory class:	II
Product code:	NPM

III. Predicate Device

Primary predicate: Geistlich Bio-Oss Collagen® (K122894)

References devices: OSSIX® PLUS (K160281), OSSIX® VOLUMAX (K153549)

IV. Device Description

OSSIX™ BONE is packed in a double blister and an outer cardboard box and is sterilized by ethylene oxide; the shelf life of the device is 36 months.

{4}------------------------------------------------

datumdental

OSSIX™ BONE is available in the following sizes: 0.125 CC (5x5x5 mm), 0.25 CC . (5x5x10 mm) and 0.5 CC (5x10x10 mm).

V. Indications for Use

OSSIX™ BONE is intended for the following uses:

Augmentation or reconstructive treatment of the alveolar ridge; .
Filling of 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).

VI. Comparison of Technological Characteristics with the Predicate Device

OSSIX™ BONE has the same intended use and indications for use and similar technological characteristics as the predicate device, Geistlich Bio-Oss Collagen® (K122894). Both products are similar in their chemical composition (porcine type I collagen and crystalline hydroxylapatite), their structure (porous spongoius matrix made of hydroxylapatite particles embedded in a lattice network of collagen fibers), and mode of action (osteoconductive bone grafting material that acts as a scaffold for new bone growth and is slowly resorbed and replaced by new bone). Both products are designed as sterile, biodegradable, biocompatible, hydrophilic, moldable, trimmable, highly porous spongious matrices.

As outlined in more detail in the table below, the subject device differs slightly from the predicate device by the HA:collagen ratio, HA source (synthetic versus bovine), particle size, the sterilization method, and product size. The technological differences between the two products in composition, material characteristics and sterilization methodology do not affect the product performance as was demonstrated by the biocompatibility, bench, and animal studies.

Thus, the subject device is substantially equivalent to the predicate device.

{5}------------------------------------------------

dətumdentəl

Feature	OSSIX™ BONE	Geistlich Bio-Oss Collagen®
Intended use/Indications foruse	• Augmentation or reconstructivetreatment of the alveolar ridge;• Filling of periodontal defects;• Filling of defects after root resection,apicoectomy and cystectomy;• Filling of extraction sockets to enhancepreservation of the alveolar ridge;• Elevation of the maxillary sinus floor;• Filling of periodontal defects inconjunction with products intended forGuided Tissue Regeneration (GTR)and Guided Bone Regeneration (GBR);• Filling of peri-implant defects inconjunction with products intended forGuided Bone Regeneration (GBR).	• Augmentation or reconstructivetreatment of the alveolar ridge;• Filling of infrabony periodontal defects;• Filling of defects after root resection,apicoectomy, and cystectomy;• Filling of extraction sockets to enhancepreservation of the alveolar ridge;• Elevation of the maxillary sinus floor;• Filling of periodontal defects inconjunction with products intended forGuided Tissue Regeneration (GTR) andGuided Bone Regeneration (GBR);• Filling of peri-implant defects inconjunction with products intended forGuided Bone Regeneration (GBR).
Mode of action	Conductive bone grafting material	Conductive bone grafting material
Design	Sterile, biodegradable, biocompatible,hydrophilic, moldable, trimmble, highlyporous spongious matrix	Sterile, biodegradable, biocompatible,hydrophilic, moldable, trimmble, highlyporous spongious matrix
Compositionand source ofmaterials	Crystalline synthetic hydroxyapatite(80%) combined with porcine type Icollagen (20%)	Crystalline bovine derived hydroxyapatite(90%) combined with porcine type Icollagen (10%)
Porosity	High porosity	High porosity
Density	2-3 g/cm³	2-3 g/cm³
Particle size	1 - 10 μm	250 - 1000 μ
Form	Block	Block
Max load	About 40 N	About 40 N
Sterility	ETO	r-irradiation
Resorptionprofile	Slow resorption	Slow resorption
Prescriptiondesignation	Rx	Rx
Reusability	Single use only	Single use only
Product Size	0.125 cc0.25 cc0.5 cc	100 mg block250 mg block500 mg block
Unit package	Double blister	Double blister
Environment ofuse	OSSIX™ BONE should only be used bytrained dentists or oral surgeons.	Geistlich Bio-Oss Collagen® should onlybe used by trained dentists or oralsurgeons.
Intended patientpopulation	Adults	Adults
Frequency andduration of use	Routine procedure	Routine procedure
Shelf life	The expiration date of the device isindicated on the outer box and theinternal blister. The product has a 36-month shelf life.	The expiration date of the device isindicated on the outer box and theinternal blister.

{6}------------------------------------------------

datumdental

VII. Summary of Data to Support Substantial Equivalence

The following performance data were provided in support of the substantial equivalence determination.

Biocompatibility testing

The biocompatibility evaluation of OSSIX™ BONE was conducted in accordance with the FDA Guidance Use of International Standard ISO 10993-1, 2016, and International Standard ISO10993-1:2009 (Cor 1:2010) Biological Evaluation of Medical Devices -Part 1: Evaluation and Testing. The final sterile device was tested for:

cytotoxicity, ●
pyrogenicity, ●
sensitization, .
. intracutaneous reactivity,
genotoxicity,
implantation,
systemic toxicity (acute), subchronic toxicity, ●
chronic toxicity. .

OSSIX™ BONE is categorized as an implant device in contact with bone/tissue.

Sterility validation

The sterilization process is established and validated according to:

ISO 11135:2014 Sterilization of health-care products -- Ethylene oxide --. Requirements for the development, validation and routine control of a sterilization process for medical devices.
The ability of the packaging to maintain the sterility of the product was demonstrated in packaging and shelf life studies.

Viral inactivation studies were conducted to demonstrate the ability of the manufacturing process to remove or inactivate viruses.

In vitro product characterization

The in vitro product characterization testing was performed to demonstrate substantial equivalence of the subject device to its predicate device, as summarized in the table below.

{7}------------------------------------------------

dətumdental

Test	Method
Scanning ElectronMicroscope (SEM)	Microscopic appearance of OSSIXTM BONE and the predicate was
	performed using A Scanning Electron Microscope.
X-ray Diffraction(XRD)	The crystalline structure of the hydroxylapatite of OSSIXTM BONE and
	the predicate was measured using an XRD instrument.
Mechanicalproperties(compression)	The capability of OSSIXTM BONE and Geistlich Bio-Oss Collagen® to
	withstand pressure (compression resistance) was tested on using a tensile
	machine.
Chemical Analysisbefore and aftermanufacturingprocess	Elemental analysis of OSSIXTM BONE and Geistlich Bio-Oss Collagen®for calcium, oxygen and phosphorus was performed by means of energy-dispersive X-ray spectroscopy (EDS).
Infra-Redspectroscopybefore and aftermanufacturingprocess	The FT-IR (Fourier Transform Infrared spectroscopy) analysis ofOSSIXTM BONE and Geistlich Bio-Oss Collagen® was performed byusing a Fourier transform infrared spectroscopy (FTIR)spectrophotometer.
Amino acidanalysis	Amino acid analysis was performed using an amino acid analyzer.
Porosity, density	Mercury intrusion porosity meter.

The HA component conforms to the following standards:

ISO 13779-3:2008, Implants for surgery - Hydroxyapatite - Part 3: Chemical analysis and characterization of crystallinity and phase purity;
. ASTM F1185-3:2014, Standard specification for composition of Hydroxylapatite for surgical implants.

Animal study

An in vivo animal study was conducted in an L-shape buccal mandibular defect model system in Beagle dogs to evaluate the in vivo performance and degradation of the device to support substantial equivalence. The study was conducted on 19 animals followed up for 1, 3 and 6 months. The performance of the subject OSSIX™ BONE in this study was compared to the predicate device, Geistlich Bio-Oss Collagen®, using a cleared OSSIX™ PLUS membrane in both treatments. The subject and predicate devices performed similarly in an L-shape buccal mandibular defect model system in Beagle dogs.

VIII. Conclusion

The subject and predicate devices have the same intended use/indications for use and substantially similar technological characteristics and principles of operation. In addition, minor technological differences between the two products do not affect the product performance, as supported by the results of the non-clinical data provided within the 510(k) submission, as summarized above. Therefore, the subject OSSIX™ BONE is substantially equivalent to the predicate device.

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.