OsOpia is a synthetic, > 90% TCP (Tri-Calcium Phosphate - Ca3(PO4)2) and < 10% Hydroxyapatite (Ca10(PO4)6 (OH)2) resorbable micro-structured bone grafting material for the repair of bony defects. OsOpia induces and guides the three-dimensional regeneration of bone in the defect site into which it is implanted. Rigid fixation techniques are recommended as needed to assure stabilization of the defect in all planes (e.g. bioresorbable barrier membranes). When placed next to viable host bone, new bone will be deposited on the surface of the implant resorbs and is replaced by bone during the natural process of bone remodelling.

OsOpia is gamma sterilized, comes in several sizes in granular form, and is double sterile packaged for single use only.

AI/ML Overview

The provided text describes the regulatory clearance for the OsOpia Synthetic Bone Void Filler. It does not, however, describe the acceptance criteria of a device (e.g., an AI/ML algorithm or diagnostic tool) in the typical sense of performance metrics like sensitivity, specificity, or F1-score. Instead, it details the criteria and studies used to demonstrate substantial equivalence for a medical device (a bone grafting material) to existing legally marketed predicate devices, as required for a 510(k) submission to the FDA.

Therefore, many of the requested items (sample sizes for test sets, data provenance, number of experts for ground truth, adjudication methods, MRMC studies, standalone performance, training set details) are not applicable in the context of this traditional medical device submission, which is not for an AI/ML device.

However, I can extract the relevant information from the provided document regarding how the device (OsOpia Synthetic Bone Void Filler) met the criteria for substantial equivalence.

Here's a breakdown based on the document:

1. Table of "Acceptance Criteria" (for Substantial Equivalence) and Reported Device Performance

Criterion Type	Description of Criterion (as implied by FDA 510(k) process for this device type)	Reported Device Performance (OsOpia)
Biocompatibility	Compliance with ISO 10993-1 and FDA Guidance for biological evaluation of medical devices (including cytotoxicity, irritation/sensitization, systemic toxicity, genotoxicity, implantation, and hemocompatibility, as applicable).	Assessed using ISO 10993-5 (cytotoxicity), ISO 10993-6 (local effects after implantation), ISO 10993-9 (degradation of materials), ISO 10993-10 (irritation and skin sensitization), and ISO 10993-11 (systemic toxicity). Found to be biocompatible per ISO 10993-1.
Sterilization Validation	Sterility Assurance Level (SAL) of 10^-6 for devices sterilized by gamma irradiation.	Validated in accordance with ISO 11137-1 and ISO 11137-2 to a sterility assurance level of 10^-6.
Shelf Life	Demonstration of product and packaging stability over the claimed shelf life, commonly through accelerated and real-time aging studies. Parameters like physical integrity, and product characteristics (e.g., chemical composition, functional properties) should be maintained.	Assigned based on accelerated and real-time aging studies of both packaging and product. Packaging tested with burst (ASTM F1140), peel (ASTM F88), and gross leak (ASTM F2096) tests. Product stability assessed by monitoring color, XRD, SEM, and porosity.
Bioburden/Pyrogenicity	Adherence to specifications for microbial load (bioburden) and absence of pyrogenic substances (bacterial endotoxin).	Verification batches met specifications for bioburden and pyrogenicity. Bacterial endotoxin testing (LAL method, USP<85>) showed the device meets FDA established endotoxin limits.
Material Characterization	Demonstration of equivalent chemical composition, physical properties, and performance characteristics to predicate/reference devices through standardized testing. This typically includes identification of components, structural analysis, and functional assessments relevant to the device's intended use.	Performed in accordance with ASTM F1088. Included: X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) for chemical composition; inductively coupled plasma/mass spectroscopy (ICP/MS) for trace elemental analysis; dissolution for in vitro calcium release rate; and mercury intrusion porosimetry for porosity. Analytical characterization demonstrated equivalent chemical composition, physical properties, and performance to predicate/reference devices.
Animal Study Performance	Demonstration of suitable performance as a bone grafting material in a relevant animal model for the intended use, showing bone formation and integration.	Evaluated in a sheep model for intraoral maxillary sinus floor augmentation surgery. Results demonstrated suitable performance as a bone grafting material for maxillary sinus augmentation.
Clinical Performance	For bone grafting materials, this often involves demonstrating suitable clinical outcomes such as new bone formation, implant survival rates in procedures where the graft is used, and absence of serious adverse events, to show safety and effectiveness comparable to marketed devices, especially for the stated indications (extraction sockets, maxillary sinus augmentation).	Six clinical studies (all prospective, one randomized, others single-arm) involving 90 patients were used. No serious adverse events reported. Two studies (at 5-6 months post-implantation) showed equal or greater new bone formation than control via bone histology. Four studies evaluated implant placement survival, reporting a survival rate of ≥96%. Demonstrated performance for socket extraction and maxillary sinus augmentation.
Indications for Use	The intended use and indications for use should be substantially equivalent to a predicate device, or any differences should not raise new questions of safety or effectiveness. The range of use (e.g., granule size) should be within or narrower than that of the predicate.	Proposed indications (extraction sockets and maxillary sinus augmentation) are narrower than the primary predicate (which includes root resection, apicoectomy, cystectomy, and periodontal defects in addition to sockets and sinus augmentation), raising no new questions of safety/effectiveness. Granule size range (250-1000 µm) is within the predicate's range (200-2000 µm) and narrower, thus raising no new safety/effectiveness issues.
Composition	The device's composition (e.g., ratio of β-TCP to HA) should be substantially equivalent to or reasonably compared with predicates or reference devices, without raising new safety/effectiveness concerns.	OsOpia: β-TCP >90%, HA <10%. Primary predicate (OsSatura): β-TCP 20%, HA 80%. A reference device (CuriOs™) has the same β-TCP >90%, HA <10% ratio as OsOpia. This difference in ratio from the primary predicate is addressed by comparison to a reference device with similar composition.

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

Clinical Studies (Test Set):
- Sample Size: 90 patients overall, across six clinical studies.
- Data Provenance: Not explicitly stated from which country/countries the patients originated, but the studies were prospective. One study was randomized, and the others were single-arm.

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. For this bone grafting material, the "ground truth" in clinical studies would typically be assessed by the treating surgeons, periodontists, or oral and maxillofacial surgeons, and confirmed through histological analysis (for bone formation) or clinical follow-up (for implant survival). The document does not specify the number or qualifications of experts for these assessments, but rather the results of those assessments.

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

Not Applicable. Adjudication methods like 2+1 or 3+1 are typically used for discordance resolution in image interpretation or diagnostic evaluations, which is not relevant for the assessment of a bone grafting material.

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. This is a medical device (bone grafting material), not an AI/ML diagnostic or image analysis tool. MRMC studies are not relevant here.

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

Not Applicable. This is a bone grafting material, not an algorithm.

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

Clinical Ground Truth:
- Bone Histology: Used in two studies (at 5-6 months post-implantation) to assess new bone formation. This is a form of pathology/histological analysis.
- Implant Survival: Used in four studies, representing outcomes data.
- Adverse Events: Monitoring for adverse events is also a form of outcomes data/safety assessment.
Pre-clinical/Bench Ground Truth:
- Biocompatibility: Based on compliance with ISO standards.
- Sterility: Based on compliance with ISO standards and SAL testing.
- Material Properties: Based on analytical techniques like XRD, FTIR, ICP/MS, and mercury intrusion porosimetry, compared against known characteristics of similar materials (predicates).
- Animal Model Performance: Assessment of bone regeneration in a sheep model.

8. The sample size for the training set

Not Applicable. This is a traditional medical device, not an AI/ML algorithm that requires a training set. The "data" here supports substantial equivalence rather than training a model.

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

Not Applicable. See point 8.

Summary

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October 2, 2020

RevisiOs BV % Kathy Remsen Principal Consultant MRC Global 9085 East Mineral Circle, Suite 110 Centennial. Colorado 80112

Re: K201546

Trade/Device Name: OsOpia Synthetic Bone Void Filler Regulation Number: 21 CFR 872.3930 Regulation Name: Bone Grafting Material Regulatory Class: Class II Product Code: LYC Dated: July 14, 2020 Received: July 15, 2020

Dear Kathy Remsen:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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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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 of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

for

Srinivas Nandkumar, Ph.D. Director DHT1B: Division of Dental Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K201546

Device Name OsOpia Synthetic Bone Void Filler

Indications for Use (Describe)

OsOpia is a bone grafting material indicated for use in the specific treatment of extraction sockets and maxillary sinus augmentation procedures.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

OsOpia Synthetic Bone Void Filler October 1, 2020

Company:	RevisiOs BVProfessor Bronkhorstlaan 10, building 483723 MB BilthovenThe Netherlands
Primary Contact:	Kathy RemsenPhone: 901-606-4856
Company Contact:	Hen Baron+31-30-740450hen.baron@kurosbio.com
Trade Name:	OsOpia Synthetic Bone Void Filler
Common Name:	Bone Grafting Material, Synthetic
Classification:	II
Regulation Number:	872.3930
Panel:	Dental
Product Code(s):	LYC

Device Description:

OsOpia is gamma sterilized, comes in several sizes in granular form, and is double sterile packaged for single use only.

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Indications for Use: OsOpia is a bone grafting material indicated for use in the specific treatment of extraction sockets and maxillary sinus augmentation procedures.

Substantial Equivalence: OsOpia was demonstrated to be substantially equivalent in indications and design characteristics to the following devices previously cleared by the FDA.

Primary Predicate:

OsSatura™ Dental, IsoTis Orthobiologics Inc (K042706) .

Reference Devices:

CuriOs™, Progentix Orthobiology BV (K090641) ●
. MagnetOs, Xpand Biotechnology BV (K161859)

Device Type	SUBJECT DEVICE	PRIMARY PREDICATE	REFERENCE DEVICE	REFERENCE DEVICE
Name	OsOpia Synthetic BoneVoid Filler	OsSatura™ Dental	CuriOs™	MagnetOs
Manufacturer	RevisiOs B.V.	IsoTis OrthobiologicsInc	Progentix OrthobiologyB.V.	XpandBiotechnology B.V.
510(k) Clearance	Subject Device	K042706	K090641	K161859
Intended Use
Indication	-Extraction socket-Sinus augmentation	-Root resection,apicoectomy andcystectomy-Extraction sockets toenhance preservationof the alveolar ridge,-Elevation of maxillarysinus floor-Treatmentof periodontaldefects.	Orthopedic (posterolateralspine as graft extender andpelvis)	Orthopedic (posterolateralspine as graft extender)
Product Code	LYC	LYC	MQV	MQV
Composition
Calcium salts	β-TCP >90%HA <10%	β-TCP: 20%HA: 80%	β-TCP >90%HA <10%	β-TCP 65-75%;HA 25-35 %
Physical Properties
Form	Irregularly shaped granules
GranuleSize	250-1000 μm	200-2000 μm	150-500 μm, 500-1000 μm, 1-2mm,1-4 mm	150-500 μm, 250-1000μm,500-1000 μm, 1-2 mm, 2-4mm
Package Sizes	0.5-5cc	Not Available	0.5-20cc	0.5-20cc
Other Properties
Biocompatibility	Biocompatible per ISO 10993-1
Single use	Yes
Sterilization	Gamma Irradiation

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While the Indications for Use statements differ for the proposed and predicate devices, they share the same intended use as a bone grafting material to fill various types of bone defects. The proposed indications for OsOpia are narrower than the primary predicate; there are no new questions of safety or effectiveness raised by the OsOpia indications. The main difference between OsOpia and the primary predicate is the ratio of B-TCP to HA. However, a reference device is provided with the same 0-TCP/HA ratio as OsOpia. The granule size range also differs between OsOpia and the primary predicate; however, the OsOpia granule size range is within the range of the predicate. Because the OsOpia granule size range is narrower than the predicate, there are no new issues of safety or effectiveness due to this difference.

Biocompatibility Testing

The biocompatibility of the device was assessed using the methodology described in ISO 10993-1 and FDA Guidance, "Use of International Standard ISO 10993-1, Biological Evaluation of medical devices - Part 1: Evaluation and testing within a risk management process." Evaluation included ISO 10993-5, ISO 10993-6, ISO 10993-9, ISO 10993-10 and ISO 10993-11.

Sterilization Validation

The sterilization of OsOpia using gamma irradiation was validated in accordance with ISO 11137-1 and ISO 11137-2 to a sterility assurance level of 10-6.

Shelf Life

The shelf life of OsOpia was assigned based on accelerated and real time aging studies of both the packaging and the product. The packaging was tested using burst test (ASTM F1140), peel test (ASTM F88), and gross leak test (ASTM F2096). The product stability was assessed by monitoring color, XRD, SEM, and porosity.

Bioburden/Pyrogenicity

Verification batches of OsOpia met specifications for bioburden and pyrogenicity. Bacterial endotoxin testing was performed in accordance with USP<85> using the limulus amebocyte lysate (LAL) method and showed that the device meets the endotoxin limits of established FDA guidelines.

Bench testing

Material characterization was performed in accordance with ASTM F1088 and included the following:

· chemical composition was analyzed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR)
· trace elemental analysis was performed by inductively coupled plasma/mass spectroscopy (ICP/MS),
· dissolution was performed to evaluate the in vitro calcium release rate, and
· porosity was measured by mercury intrusion porosimetry.

The analytical characterization demonstrated equivalent chemical composition, physical properties and performance characteristics for the subject OsOpia and predicate/reference devices.

Animal Studies

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The performance of OsOpia was evaluated in a sheep model for an intraoral maxillary sinus floor augmentation surgery. The results of the study demonstrated that the performance of the subject device was suitable as a bone grafting material for maxillary sinus augmentation.

Clinical Data

Six clinical studies using OsOpia in adult patients were used to support the substantial equivalence. All of the studies were prospective studies. One study was randomized. The other studies were single-arm. Overall, 90 patients were evaluated. No serious adverse events were reported for OsOpia. Two studies evaluated bone histology at 5-6 months post implantation with OsOpia demonstrating equal or greater new bone formation than the control. Four of the studies evaluated implant placement survival. The implant survival rate was ≥96% in the clinical studies. The human studies demonstrate the performance of OsOpia for socket extraction and maxillary sinus augmentation indications.

Conclusion

Based on pre-clinical and clinical data, the bench testing results and the comparison to the predicate and reference devices, the subject device is determined to be 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.