NuROs Bone Graft Substitute is an implant intended to fill bony voids or gaps of the skeletal system, i.e., extremities and pelvis. These osseous defects are surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure. NuROs Bone Graft Substitute resorbs and is replaced with bone during the healing process.

Device Description

NuROs Bone Graft Substitute is an osteoconductive bone void filler with interconnective pore system. It is made of synthetic beta-tricalcium phosphate (B-TCP) indicated for bone void filling. It is suitable for individuals with bone voids of gaps, caused by surgery or trauma.

NuROs Bone Graft Substitute is available in granule type and block type with different volumes which are 1c.c, 2.5c.c, 5c.c, 10c.c, 20c.c, 25c.c and 30c.c. Granule types are provided in 0.2 ~ 0.5mm, 0.5 ~ 1mm, 1 ~ 2mm and 3mm of particle size. Block type is provided in 5mm x 5mm x 10mm, 5mm x 20mm, 10mm x 10mm x 10mm and 10mm x 25mm x 25mm size.

NuROs Bone Graft Substitute is pure ß-TCP with all crystalline phase. The Ca/P ratio is 1.5. The structure of the material is multidirectional interconnective porosity with >70% porosity. The propose device does not impart mechanical strength to surgical site.

The NuROs Bone Graft Substitute is gamma irradiated and provided for single use only.

AI/ML Overview

The provided text describes the 510(k) summary for the NuROs Bone Graft Substitute, focusing on its substantial equivalence to a predicate device. Here's a breakdown of the acceptance criteria and the study information as requested:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria/Tests	NuROs Bone Graft Substitute Reported Performance
Biocompatibility	ISO 10993-1 (Evaluation and testing)	"Testing performed on NuROs shows biocompatible with no significant adverse observations of any kind." "As a biomaterial, beta-TCP has consistently proven to be non-toxic, non-allergenic, and biocompatible and elicits no inflammation. No adverse system effects have been observed."
	ISO 10993-3 (Genotoxicity, carcinogenicity, reproductive toxicity)	(Covered by general biocompatibility statement)
	ISO 10993-5 (In vitro cytotoxicity)	(Covered by general biocompatibility statement)
	ISO 10993-6 (Local effects after implantation)	(Covered by general biocompatibility statement and animal test, which includes histomorphometry)
	ISO 10993-10 (Irritation and skin sensitization)	(Covered by general biocompatibility statement)
	ISO 10993-11 (Systemic toxicity)	(Covered by general biocompatibility statement)
	ISO 10993-12 (Sample preparation and reference material)	(Standard applied for testing)
Sterilization & Shelf Life	ISO 11737-1,-2; ISO 11137-2; ASTM F1980-07; ASTM F88-85; ASTM F1140:2000; ASTM D4332:2001; ASTM 1608; ASTM F1929-98 (microbiological methods, sterilization dose, accelerated aging, seal strength, pressurization failure, conditioning, microbial ranking, dye penetration)	(Implied to meet standards as part of overall safety and effectiveness assessment). The device is "gamma irradiated and provided for single use only."
Performance (Bench Tests)	Chemical Composition (pure beta-TCP, crystalline phase, no impurities)	"composed of pure beta-TCP and all crystalline phase, no other impurities were presented."
	Elemental Analysis (Ca/P ratio)	"the ratio of Ca to P was approximately 1.5." (Matches predicate's stated 1.5)
	Structure Observation (porous structures)	"has similar porous structures." (Predicate: multidirectional interconnected porosity, NuROs: multidirectional interconnective pore system with >70% porosity)
	Specification of Device Porosity (>70% porosity, pore size)	">70% porosity." "Pore size: 70 ~ 400 μm" (Predicate: 30 ~ 400 μm, slight difference acknowledged but deemed not problematic).
	TGA-residue Analysis (no unsintered material/trace elements)	"no unsintered material or any trace elements."
	Ultra Trace Elements (concentrations in accordance with standard)	"the ultra-trace elements concentrations were in accordance with the standard."
	pH Test	(Passed, results showed "same characteristics as the predicate device")
Performance (Animal Test)	Degradation rate, bone-defect interface, and overall healing comparable to predicate device. Safety and effectiveness.	"the data showed that the proposed device, NuROs Bone Graft Substitute is as effective as the predicate device." "A series of safety tests were performed to assess the safety and effectiveness of the NuROs Bone Graft Substitute."
Conformity to Standard	ASTM F1088-04a Standard Specification for Beta-Tricalcium Phosphate for Surgical Implantation	"NuROs Bone Graft Substitute conforms to the recognized consensus standard specification for surgically implantable beta-tricalcium phosphate."
Overall Conclusion	Meet requirements of pre-defined acceptance criteria and intended uses regarding safety and effectiveness.	"All the test results demonstrate NuROs Bone Graft Substitute meets the requirements of its pre-defined acceptance criteria and intended uses." "The proposed device is substantially equivalent to the predicate device in design, operation, intended use and performance claims." "can be concluded that NuROs Bone Graft Substitute is as safe and effective as the predicate device."

2. Sample size used for the test set and the data provenance

Animal Test Specifics:
- Sample Size: Not explicitly stated as a number of animals in the provided text. It mentions "porcine models" and "Each tibia of the pig was drilled with two blind-ended tunnels" where "different bone grafts were implanted into each tunnel of each leg." This implies at least one pig, but likely more, given common practice in animal studies to achieve statistical power. However, no specific number is given.
- Data Provenance: Porcine models (Pigs). The study is prospective in terms of observing the effects after implantation.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the text. The animal study involved histomorphometry and imaging (CT Scans, X-rays), which would typically be evaluated by experts (e.g., veterinary pathologists, radiologists), but their number or qualifications are not mentioned.

4. Adjudication method for the test set

The text does not describe any adjudication method. It states that CT Scans, X-rays, and Histomorphometry were taken to observe and assess the results. This implies expert interpretation, but no specific method for resolving discrepancies among multiple readers (if any) is detailed.

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

No MRMC comparative effectiveness study was done. This submission is for a bone graft substitute (a material implant), not an AI diagnostic/imaging device. Therefore, the concept of human readers improving with AI assistance is not applicable.

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

Not applicable. As stated above, this is a material implant, not an algorithm or AI device.

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

For the animal study, the "ground truth" for assessing effectiveness (degradation rate, bone defects, healing) was established through a combination of:
- Direct observation: Measurements of defect diameters.
- Imaging: CT Scans and X-rays.
- Pathology/Histology: Histomorphometry.
- Comparative data: Effectiveness was assessed by comparing the NuROs device to the predicate device within the porcine models.

8. The sample size for the training set

Not Applicable. This is a material implant, not a software/AI device that requires a training set.

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

Not Applicable. No training set was used for this type of device.

Summary

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Image /page/0/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, with three intertwined snakes and a staff. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus.

February 17, 2015

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

Oriental Resources Development Limited % Mr. Michael Lee AcmeBiotechs Company, Limited No. 45 Minsheng Road, Danshui Town New Taipei City, Taiwan 251 Republic of China

Re: K140913

Trade/Device Name: NuROs Bone Graft Substitute Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MQV Dated: December 31, 2014 Received: January 8, 2015

Dear Mr. Lee:

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

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Page 2 - Mr. Michael Lee

(21 CFR Part 807); labeling (21 CFR Part 801); medical device 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 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 yours,

Mark N. Melkerson -S

Mark N. Melkerson Director Division of Orthopedic Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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NuROs Bone Graft Substitute 510(k) Number: K140913/S002

Indications for Use

510(k) Number (if known): K140913

NuROs Bone Graft Substitute Device Name:

Indications for Use:

Prescription Use (Part 21 CFR 801 Subpart D)

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)

Page 1 of

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NuROs Bone Graft Substitute 510(k) Number: K140913/S002

Section 5

510(k) Summary

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NuROs Bone Graft Substitute 510(k) Number: K140913/S002

510(k) Summary

5.1	Type of Submission:	Traditional
5.2	Preparation Date:	25th March 2014
5.3	Submitter:	Oriental Resources Development Limited
	Address:	2F., No.30, Hexing Rd., Hukou Township,
		Hsinchu County 303, Taiwan (R.O.C.)
	Phone:	+886-3-5997135 Ext. 843
	Fax:	+886-3-6208066
	Contact:	Wei-Chun Chang (raychang@feg.com.tw)
	Registration number:	3010275504

5.4 Identification of the Device:

Proprietary/Trade name:	NuROs Bone Graft Substitute
Classification Name:	Resorbable calcium salt bone void filler device
Device Classification:	II
Regulation Number:	888.3045
Panel:	Orthopedic
Product Code:	MQV

5.5 Identification of the Predicate Device:

Predicate Device Name:	BIOSORB® Resorbable Bone Void Filler
Manufacturer:	Sciences et Bio Matériaux
Product Code:	MQV
510(k) Number:	K021963

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5.5 Intended Use and Indications for Use of the subject device.

5.6 Device Description

The NuROs Bone Graft Substitute is gamma irradiated and provided for single use only.

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NuROs Bone Graft Substitute 510(k) Number: K140913/S002

5.7 Non-clinical Testing

5.7.1 Biocompatibility

According to ISO 10993 <> and to the type of medical device (long-term implantable medical device, bone/tissue contact) the following biologic effects have been investigated:

A Cytotoxicity
A Sensitization
Intracutaneous Irritation reactivity
System Toxicity (Acute) >
Subchronic Toxicity (Subacute Toxicity)
Genotoxicity
A Implantation
Pyrogenicity

Testing performed on NuROs shows biocompatible with no significant adverse observations of any kind.

5.7.2 Bench test

A series of bench tests were conducted on the proposed device, NuROs Bone Graft Substitute.

A Chemical Composition
Elemental Analysis
A Structure Observation
Specification of Device Porosity
TGA-residue Analysis
Ultra Trace Elements
A pH Test
Pore Size Distribution

The results showed that the proposed device have the same characteristics as the predicate device.

5.7.3 Animal Test

The animal test was conducted to observe the difference in degradation rate, bone-defect interface and the state of overall healing in the animal between

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proposed device and predicate device. The bone grafts were implanted into porcine models and tracked for a period of time. Each tibia of the pig was drilled with two blind-ended tunnels and different bone grafts were implanted into each tunnel of each leg. CT Scans, X-rays and Histomorphometry were taken in order to observe and assess the results. The diameters of the defects were measured and recorded at each point in time to illustrate the degradation rate of the implant and healing rate of the bone defect. After the 1st and the 3rd month, the data showed that the proposed device, NuROs Bone Graft Substitute is as effective as the predicate device.

A series of safety tests were performed to assess the safety and effectiveness of the NuROs Bone Graft Substitute.

Testing Item	Standard and regulations applied
Biocompatibility	ISO 10993-1 Biological evaluation of medical devices -- Part I : Evaluation and testing.
	ISO 10993-3 Biological evaluation of medical devices -- Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
	ISO 10993-5 Biological evaluation of medical devices -- Part 5: Tests for in vitro cytotoxicity
	ISO 10993-6 Biological evaluation of medical devices -- Part 6: Tests for local effects after implantation
	ISO 10993-10 Biological evaluation of medical devices -- Part 10: Tests for irritation and skin sensitization
	ISO 10993-11 Biological evaluation of medical devices -- Part 11: Tests for systemic toxicity
	ISO 10993-12 Biological evaluation of medical devices -- Part 12: Sample preparation and reference material
Sterilization andshelf life	ISO 11737-1:2006 Sterilization of medical devices - Microbiological methods - Part 1: Determination of a population of microorganisms on products
	ISO 11737-2:2009 Sterilization of medical devices - Microbiological methods – Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization

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NuROs Bone Graft Substitute 510(k) Number: K140913/S002

	process
	ISO 11137-2:2009 Sterilization of health care products –Radiation – Part 2: Establishing the sterilization dose
	ASTM F1980-07 Standard Guide for Accelerated Aging of SterileBarrier Systems for Medical Devices
	ASTM F88-85 Standard Test Method for Seal Strength of FlexibleBarrier Materials
	ASTM F1140:2000 Standard Test Methods for InternalPressurization Failure Resistance of Unrestrained Packages forMedical Applications.
	ASTM D4332: 2001 Standard practice conditioning containers,packages or packaging components for testing
	ASTM 1608 Standard Test Method for Microbial Ranking ofPorous Packaging Materials (Exposure Chamber Method)
	ASTM F1929-98 Standard test Method for Detecting Seal Leaksin Porous Medical Packaging by Dye Penetration
Performance	ASTM F1088-04a Standard Specification for Beta-TricalciumPhosphate for Sugical Implantation

NuROs Bone Graft Substitute conforms to the recognized consensus standard specification for surgically implantable beta-tricalcium phosphate. The biocompatibility of beta-TCP implants is also well documented. As a biomaterial, beta-TCP has consistently proven to be non-toxic, non-allergenic, and biocompatible and elicits no inflammation. No adverse system effects have been observed.

All the test results demonstrate NuROs Bone Graft Substitute meets the requirements of its pre-defined acceptance criteria and intended uses.

5.8 Clinical Testing

No clinical test data was used to support the decision of safety and effectiveness.

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NuROs Bone Graft Substitute 510(k) Number: K140913/S002

5.9 EMC and Electrical safety

The devices do not require EMC/Electrical Safety evaluation.

5.10 Substantial Equivalence Determination

The NuROs Bone Graft Substitute has similar intended use, fundamental scientific technology, and technological characteristics with the predicate device. Information described below can demonstrate the NuROs Bone Graft Substitute is substantial equivalent to the predicate device.

Item	Predicate Device	Subject Device
Trade name	BIOSORB® Resorbable Void Filler	NuROs Bone Graft Substitute
K number	K021963
Regulation no./ Class	888.3045 / II	888.3045 / II
Classification name	Resorbable calcium salt bone voidfiller device	Resorbable calcium salt bonevoid filler device
Product code/Device panel	MQV / Orthopedic	MQV / Orthopedic
Intended use	BIOSORB® Resorbable Void Filleris a resorbable calcium salt bone voidfiller intended to fill bony voids orgaps of the skeletal system (i.e. theextremities, spine and pelvis,) causedby trauma or surgery, that are notintrinsic to the stability of the bonystructure.BIOSORB® Resorbable Void Fillerdoes not possess sufficientmechanical strength to supportreduction of a defect prior to soft andhard tissue ingrowth. Rigid fixationtechniques are recommended asneeded to assure stabilization of thedefect in all plans.	NuROs Bone Graft Substitute isan implant intended to fill bonyvoids or gaps of the skeletalsystem, i.e., extremities andpelvis. These osseous defects aresurgically created or the result oftraumatic injury to the bone andare not intrinsic to the stabilityof the bony structure. NuROsBone Graft Substitute resorbsand is replaced with bone duringthe healing process.

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NuROs Bone Graft Substitute 510(k) Number: K140913/S002

Biocompatibility	Established	Established
Sterility	Sterilize (gamma radiation)Single use only	Same as predicate
Similarity
Structure	multidirectional interconnectedporosity structure	Same as predicate device
Chemical composition	β-Tricalciumphosphate(Ca3(PO4)2)	Same as predicate device
Mechanical Strength	Does not impart mechanicalstrength to surgical site	Same as predicate device
Porosity of material	70%	70%
Ca/P ratio	1.5	1.5
Pore size	30 ~400 μm	70 ~400 μm
Differences
Shape andSize	Granule type	vary in particle size(0.6mm to 3mm)	• 0.2 ~ 0.5mm• 0.5 ~ 1mm• 1 ~ 2mm• 3mm
	Block type(LxHxW mm)	10 x 10 x 2515 x10 x 430 x 20 x10	5 x 5 x 105 x 5 x 2010 x 10 x 1010 x 25 x 25
	Cube type	vary in particle size( 5mm to 10mm)	-
	Macroporouscubes	4mm x 4mm x 4mm	-
	Stick type	5mm x 5mm x 10mm,5mm x 5mm x 20mm	-
	Cylinder type	6mm to 8mm	-

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5.11 Similarity and differences

There were some differences between the proposed device and predicate device. The proposed device was designed in two type of shape (granule and block) with different particle size, predicate device was designed in six types (granule, block, cube, macroporous cube, stick and cylinder).

A series of bench tests were performed which included the chemical composition, elemental analysis, structure observation, specification of device porosity, TGA-residue analysis, ultra trace elements testing and pH testing. The results showed that same as the predicate device, the proposed device was composed of pure beta-TCP and all crystalline phase, no other impurities were presented, the ratio of Ca to P was approximately 1.5, has similar porous structures, no unsintered material or any trace elements and the ultra-trace elements concentrations were in accordance with the standard. The animal test data also showed that the proposed device, NuROs Bone Graft Substitute is as effective as the predicate device.

The proposed device has tested on safety and performance tests and the test results were complied with the test requests. Therefore, the differences of proposed device and predicate device didn't raise any problems of safety or effectiveness. The proposed device is substantially equivalent to the predicate device in design, operation, intended use and performance claims.

5.12 Conclusion

After analyzing bench and animal tests, device description and intended use/indications for use, it can be concluded that NuROs Bone Graft Substitute is as safe and effective as the predicate device.

Regulation Number and Section

§ 888.3045 Resorbable calcium salt bone void filler device.

(a)
Identification. A resorbable calcium salt bone void filler device is a resorbable implant intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure.(b)
Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA.” See § 888.1(e) of this chapter for the availability of this guidance.