Bonalive® Orthopedics granules is an implant intended to fill bony voids or gaps of the skeletal system. (i.e., extremities and pelvis). These osseous defects may be the result of benign bone cysts and tumors (in adults and pediatric patients > 6 years old), are surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure. Bonalive® Orthopedics granules resorbs and is replaced with bone during the healing process.

Device Description

Bonalive® Orthopedics granules is composed of osteostimulative calcium-phosphoroussodium-silicate (glass 553P4) granules (size 0.5-0.8 mm or 1.0-2.0 mm) and is a sterile medical device. This synthetic, osteoconductive material is comprised of SiO2, Na2O, CaO and P₂O₃. Bioactive glass is characterized by its ability to attach firmly to living tissue. Other properties include its abilitate bone tissue growth, bond chemically with surrounding bone, and promote new bone formation in the implanted area.

In aqueous solution (e.g. body fluids), bioactive glass works by leaching out ions and developing a silica-gel layer which acts as a template for a calcium phosphate (CaP) precipitation. The CaP crystallizes to hydroxyapatite, which resembles the mineral phase of natural bone in its chemical composition and structure, thus enabling bonding of the bioactive glass to the surrounding bone.

The Bonalive® Orthopedics granules resorb and are replaced with bone slowly over a period of years. The bioactive glass in the Bonalive® Orthopedics granules is radiodense thus enabling postoperative radiologic evaluation.

Best results are obtained by ensuring close contact of the device with surrounding bone tissue and by carefully following the Instructions for Use.

Bonalive® Orthopedics granules is sterilized by irradiation and is available in different granule and unit sizes.

AI/ML Overview

The provided document is a 510(k) summary for the Bonalive® Orthopedics granules. It describes the device, its indications for use, and its substantial equivalence to a predicate device. However, it does not contain a study that proves the device meets specific acceptance criteria.

Instead, the document states that "No changes have been made to the subject device Bonalive® Orthopedics granules materials, manufacturing, or sterilization processes" compared to the predicate device (K191274 Bonalive® granules). Therefore, the non-clinical performance data, biocompatibility, sterility, and shelf-life testing performed on the predicate device are referenced as sufficient to support the substantial equivalence of the new device.

There is also a clear statement that "There was no clinical testing required to support the medical device as the indications for use is equivalent to the predicate device." This means no clinical study was conducted for the Bonalive® Orthopedics granules to demonstrate its performance against acceptance criteria.

Given the information provided, I cannot fulfill all parts of your request because the document explicitly states that no such study was performed for this specific device, and thus no performance data, sample sizes, expert ground truth, or MRMC studies are presented for it.

However, I can extract information regarding the type of non-clinical testing performed on the predicate device, which is considered applicable to the subject device.

Here's what can be extracted based on the document:

1. A table of acceptance criteria and the reported device performance:

This table cannot be fully completed as no specific acceptance criteria for a new study on the Bonalive® Orthopedics granules are presented, nor is new device performance data reported from such a study. The document focuses on demonstrating that the subject device is identical to the predicate in key aspects.

Acceptance Criteria	Reported Device Performance (from Predicate Testing)
Material Composition	SiO2, Na2O, CaO and P2O5 (confirmed)
Crystallinity	Tested (details not provided)
Particle Size Distribution	Tested (details not provided)
Surface Area	Tested (details not provided)
Heavy Metals	Tested (details not provided)
Apatite	Tested (details not provided)
Biocompatibility (ISO 10993)	Cytotoxicity (successfully performed)
	Sensitization (successfully performed)
	Systemic toxicity (successfully performed)
	Genotoxicity (successfully performed)
	Muscle Implantation (successfully performed)
	Pyrogen (successfully performed)
Sterilization	Conforms to EN ISO 11137 – Radiation Sterilization Validation
Packaging	Conforms to ISO 11607 - Packaging for terminally sterilized medical devices
Pyrogenicity	Non-pyrogenic
MR Safety	MR Safe

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

Sample Size: Not applicable. No new test set or study was conducted for the subject device. The predicate device's testing is referenced. The document does not specify general sample sizes for the referenced non-clinical tests.
Data Provenance: The document refers to testing performed on the predicate device, K191274 Bonalive® granules. No country of origin for the data is specified, and it relates to non-clinical laboratory testing rather than patient data (retrospective or prospective).

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

Not applicable. This device is a bone void filler, and the described testing involves material and biological safety assessments, not diagnostic performance or expert-adjudicated clinical outcomes in a new study.

4. Adjudication method for the test set:

Not applicable. No new test set requiring expert adjudication was conducted for the subject device.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done:

No. The document explicitly states "There was no clinical testing required to support the medical device." An MRMC study would be a type of clinical study.

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

Not applicable. This is a medical device (granules for bone void filling), not an AI algorithm.

7. The type of ground truth used:

For the non-clinical tests on the predicate device, the "ground truth" would be established by the scientific standards and reference methods defined by the relevant ISO standards (e.g., ISO 10993 for biocompatibility, ISO 11137 for sterilization, ISO 11607 for packaging), and the material specifications of the product (e.g., composition, particle size).

8. The sample size for the training set:

Not applicable. This is a medical device, not an AI algorithm requiring a training set.

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

Not applicable. (See #8)

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

July 11, 2023

Bonalive Biomaterials, Ltd. % Elisa Maldonado-Holmertz RA/OA Consultant Obelix Consulting, LLC 806 Jefferson St Bastrop, Texas 78602

Re: K231528

Trade/Device Name: Bonalive Orthopedics granules Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MOV Dated: May 24, 2023 Received: May 26, 2023

Dear Ms. Maldonado-Holmertz:

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.

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

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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 (QS) 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,

Jesse Muir -S

Jesse Muir, Ph.D. Assistant Director DHT6C: Division of Restorative, Repair and Trauma Devices OHT6: Office of Orthopedic Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K231528

Device Name

Bonalive® Orthopedics granules

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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☑ Prescription Use (Part 21 CFR 801 Subpart D)	□ Over-The-Counter Use (21 CFR 801 Subpart C)
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K231528 510(k) Summary

1. Submission Sponsor

Kristoffer Sibelius Business Development Manager Bonalive Biomaterials Ltd. Biolinja 12 20750 Turku Finland Email: kristoffer.sibelius@bonalive.com Tel number: +358 40 031 8013

2. Submission Correspondent

Obelix Consulting, LLC 806 Jefferson St Bastrop, TX 78602 USA Elisa Maldonado-Holmertz RA/QA Consultant Email: elisamh@obelixconsult.com Tel number: 512.431.6069

3. Date Prepared

24 May 2023

4. Device Identification

Type of 510(k) Submission:
Trade or Proprietary Name:
Common or Usual Name:
Regulation Description:
Regulation Classification:
Product Code:
Class of Device:
Review Panel:
Reason for Submission:
Prior Related Submissions:
Multiple Devices:

Traditional Bonalive Orthopedic granules Filler, Bone Void, Calcium Compound Resorbable calcium salt bone void filler device 888.3045 MQV Class II Orthopedic Labeling Change K191274 None

5. Legally Marketed Predicate Device(s)

Predicate: K191274 Bonalive® granules by Bonalive Biomaterials, Ltd. Reference: K113871 Pro-Dense Bone Graft Substitute by Wright Medical Technology, Inc.

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6. Device Description

Best results are obtained by ensuring close contact of the device with surrounding bone tissue and by carefully following the Instructions for Use.

Bonalive® Orthopedics granules is sterilized by irradiation and is available in different granule and unit sizes.

7. Indication for Use Statement

Bonalive® Orthopedics granules is an implant intended to fill bony voids or gaps of the skeletal system (i.e., extremities and pelvis). These osseous defects may be the result of benign bone cysts and tumors (in adults and pediatric patients ≥ 6 years old), are surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure. Bonalive® Orthopedics granules resorbs and is replaced with bone during the healing process.

RX Only

8. Substantial Equivalence Discussion

The following table compares the subject device to the predicate and reference devices with respect to intended use, technological characteristics and principles of operation, providing more detailed information regarding the basis for the determination of substantial equivalence.

Subject Device	Predicate Device	Reference Device
Bonalive Biomaterials, Ltd	Bonalive Biomaterials, Ltd
		Wright
		Medical
		Technology

Comparison of Characteristics

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Trade Name	Bonalive® Orthopedics granules	Bonalive® granules	Pro-Dense Bone Graft Substitute		Manufacturer	Subject Device	Predicate Device	Reference Device
510(k) Number		K191274	K113871			Bonalive Biomaterials, Ltd	Bonalive Biomaterials, Ltd	WrightMedicalTechnology
Product Code	MQV	MQV	MQV	None	Trade Name	Bonalive® Orthopedicsgranules	Bonalive® granules	Pro-DenseBone GraftSubstitutedefectscreated fromtraumaticinjury to thebone. Thepasteprovides abone graftsubstitutethat resorbsand isreplaced withbone duringthe healingprocess.The PRO-DENSE®paste curedin situprovides anopenvoid/gapfiller that canaugmentprovisionalhardware(e.g. K Wires)to helpsupport bonefragmentsduring thesurgicalprocedure.The curedpaste actsonly as atemporarysupportmedia and isnot intendedto provide
Regulation Number	888.3045	888.3045	888.3045	None
Regulation Name	Resorbable calcium salt bone void filler device	Resorbable calcium salt bone void filler device	Resorbable calcium salt bone void filler device	None
Indications for Use	Bonalive® Orthopedics granules is an implant intended to fill bony voids or gaps of the skeletal system (i.e., extremities and pelvis). These osseous defects may be the result of benign bone cysts and tumors (in adults and pediatric patients ≥ 6 years old), are surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure. Bonalive® Orthopedics granules resorbs and is replaced with bone during the healing process.	Bonalive® granules is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. Bonalive® granules is indicated to be gently packed into bony voids or gaps of the skeletal system (i.e. the extremities and pelvis). These defects may be the result of surgically created osseous defects or osseous defects created from traumatic injury to the. The product contains a bone void filler that resorbs and is replaced with bone during the healing process. When used in the extremities and pelvis, Bonalive® granules is intended to be used alone.	PRO-DENSE® resultant paste is intended for use as a bone graft substitute to be injected or digitally packed into open bone voids/gaps that are not intrinsic to the stability of bony structure of the skeletal system (i.e., the extremities and pelvis) to cure in situ . These open bone voids may be the result of benign bone cysts and tumors (in adults and pediatric patients ≥ 6 years old), surgically created osseous defects or osseous	Labeling Change from K191274Same as K113871: “may be the result of benign bone cysts and tumors (in adults and pediatric patients ≥ 6 years old)”

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Manufacturer	Subject DeviceBonalive Biomaterials, Ltd	Predicate DeviceBonalive Biomaterials, Ltd	ReferenceDeviceWrightMedicalTechnology	SignificantDifferences
Trade Name	Bonalive® Orthopedicsgranules	Bonalive® granules	Pro-DenseBone GraftSubstitute
			structuralsupportduring thehealingprocess.PRO-DENSE®is providedsterile forsingle useonly.
Rx or OTC	Rx	Rx	Rx	None
Physical Form	Amorphous, non-porousrandom-shaped particles	Amorphous, non-porousrandom-shaped particles	Resultantpaste	None -Predicate
Color	Brown	Brown	White	None –Predicate
MaterialsComposition	SiO2, Na2O, CaO and P2O5	SiO2, Na2O, CaO and P2O5	CaSO4,CaPO4	None -Predicate
Product Sizes	Granule sizes:0.5-0.8 mm1.0-2.0 mmProduct volumes:1 cc2.5 cc5 cc10 cc	Granule sizes:0.5-0.8 mm1.0-2.0 mmProduct volumes:1 cc2.5 cc5 cc10 cc	Productvolumes:4, 10, 20 cc	None -Predicate
Biocompatibility	BiocompatibleISO 10993	BiocompatibleISO 10993	BiocompatibleISO 10993	None
Sterilization	GammaSterile, SAL 10-6	GammaSterile, SAL 10-6	Ethyleneoxide	None -Predicate
Pyrogenicity	Non-pyrogenic	Non-pyrogenic	Non-pyrogenic	None
Single Use/Reuse	Single use only	Single use only	Single useonly	None
Manufacturer	Subject Device	Predicate Device	Reference Device	Significant Differences
	Bonalive Biomaterials, Ltd	Bonalive Biomaterials, Ltd	WrightMedicalTechnology
Trade Name	Bonalive® Orthopedics granules	Bonalive® granules	Pro-DenseBone GraftSubstitute
Mode of action	Works by leaching out ionsthat react with the bodyfluids transforming theglass surface chemicallyinto one that by itschemical composition andstructure resembles themineral phase found innatural bone.	Works by leaching out ionsthat react with the bodyfluids transforming theglass surface chemicallyinto one that by itschemical composition andstructure resembles themineral phase found innatural bone.	Angiogenesis. Reso-ptionof the PRO-DENSE™scaffoldreleasesboundproteins.Activeproteinsrecruit cellsto theimplantsurface.	None -Predicate
Properties	SyntheticOsteoconductive	SyntheticOsteoconductive	SyntheticOsteoconductive	None
MR Safety	MR Safe	MR Safe	MR Safe	None

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9. Non-Clinical Performance Data

The following testing was performed on the predicate K191274 Bonalive® granules. No changes have been made to the subject device Bonalive® Orthopedics granules materials, manufacturing, or sterilization processes.

Apatite
Composition Heavy Metals .
. Crystallinity
Particle Size Distribution .
Surface Area ●
Manufacturing & Specifications Validation .

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10. Biocompatibility

Biocompatibility testing was conducted in accordance with ISO-10993-1, "Biological evaluation of medical device – Part 1: Evaluation and testing within a risk management process". The following biocompatibility studies were successfully performed on the predicate K191274 Bonalive® granules. No changes have been made to the subject device Bonalive® Orthopedics granules materials, manufacturing, or sterilization processes.

Cytotoxicity
Sensitization
Systemic toxicity ●
Genotoxicity
Muscle Implantation
Pyrogen

11. Sterility and Shelf Life

EN ISO 11137 – Radiation Sterilization Validation
. ISO 11607 - Packaging for terminally sterilized medical devices

12. Clinical Performance Data

There was no clinical testing required to support the medical device as the indications for use is equivalent to the predicate device.

13. Statement of Substantial Equivalence

Bonalive® Orthopedics granules is substantially equivalent to the predicate device as it has the same design, materials, mode of action, manufacturing and sterilization processes, and technological characteristics as the previously cleared predicate device, and the subject device does not raise new questions regarding its safety and effectiveness as compared to 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.