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 surgically created osseous defects created from traumatic injury to the bone. 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.

Device Description

BonAlive® granules is composed of osteostimulative calcium-phosphorous-sodium-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 P2O5. Bioactive glass is characterized by its ability to attach firmly to living tissue. Other properties include its ability to facilitate 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® granules resorb and are replaced with bone slowly over a period of years. The bioactive glass in the BonAlive® 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® granules is sterilized by irradiation and is available in different granule and unit sizes.

AI/ML Overview

This document is a 510(k) Premarket Notification from the U.S. Food & Drug Administration (FDA) for the BonAlive® Granules device, a resorbable calcium salt bone void filler. It focuses on demonstrating substantial equivalence to a previously cleared predicate device (K071199 BonAlive Granules by Vivoxid Ltd.).

Therefore, the study design and associated information you're asking about (acceptance criteria, sample size, expert ground truth, MRMC studies, standalone performance, etc.) are not present in this document. This is because clinical performance data was not required to support the medical device's clearance.

The relevant section from the document is:

{8} Section 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. These types of devices, including the predicate devices, have been on the market for many years with a proven safety and efficacy for the use of the device. The non-clinical testing detailed in this submission supports the substantial equivalence of the device."

Instead of clinical studies, the submission relied on demonstrating substantial equivalence through:

Comparison of intended use, technological characteristics, and principles of operation to the predicate device (as detailed in {5} and {6}).
Non-Clinical Performance Data (Apatite, Composition Heavy Metals, Crystallinity, Particle Size Distribution, Surface Area, Manufacturing & Specifications Validation, all listed in {7}).
Biocompatibility testing (ISO 10993-1, including cytotoxicity, sensitization, systemic toxicity, and muscle implantation, detailed in {7}).
Sterility and Shelf Life testing (EN ISO 11137 and ISO 11607, detailed in {8}).

In summary, BigCo, the document does not contain the information you requested regarding acceptance criteria, training/test set details, expert ground truth, or clinical study specifics because such studies were not required for this 510(k) clearance based on substantial equivalence.

Summary

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Image /page/0/Picture/0 description: The image contains 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.

BonAlive Biomaterials Ltd. % Elisa Maldonado-Holmertz RA/QA Consultant Obelix Biotech Solutions 12416 Fairfax Ridge Place Austin, Texas 78738

Re: K191274

Trade/Device Name: BonAlive® 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 10, 2019 Received: May 15, 2019

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.

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

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 (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 mediation-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.

Laurence D. Coyne, 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) K191274

Device Name

BonAlive® Granules

Indications for Use (Describe)

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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Section 005 - 510(k) Summary

1. Submission Sponsor

Jimmy Lucchesi Chief Technology Officer BonAlive Biomaterials Ltd. Biolinja 12 20750 Turku Finland Email: Jimmy.Lucchesi@bonalive.com Tel number: +358 50 552 4671

2. Submission Correspondent

Obelix Consulting, LLC 12416 Fairfax Ridge Place Austin, TX 78738 USA Elisa Maldonado-Holmertz RA/QA Consultant Email: elisamh@obelixconsult.com Tel number: 512.431.6069

3. Date Prepared

10 May 2019

4. Device Identification

Type of 510(k) Submission:	Traditional
Trade or Proprietary Name:	BonAlive Granules
Common or Usual Name:	Filler, Bone Void, Calcium Compound
Regulation Description:	Resorbable calcium salt bone void filler device
Regulation Classification:	888.3045
Product Code:	MQV
Class of Device:	Class II
Review Panel:	Office of Device Evaluation (ODE)Division of Orthopedic Devices (DOD)Restorative and Repair Devices Branch (RRDB)
Reason for Submission:	New device
Prior Related Submissions:	Submission K110024 received NSE due toosteostimulation and antibacterial claims. Thiscurrent submission has removed such claims.
Multiple Devices:	None

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5. Legally Marketed Predicate Device(s)

K071199 (Rx Only) BonAlive Granules by Vivoxid Ltd. (now called BonAlive Biomaterials, Ltd.)

6. Device Description

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® granules resorb and are replaced with bone slowly over a period of years. The bioactive glass in the BonAlive® 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® granules is sterilized by irradiation and is available in different granule and unit sizes.

7. Indication for Use Statement

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 surgically created osseous defects or osseous defects created from traumatic injury to the bone. 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.

RX Only

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8. Substantial Equivalence Discussion

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

	Comparison of Characteristics
Manufacturer	SUBJECT DEVICEBonAlive Biomaterials, Ltd	PREDICATE DEVICEVivoxid Ltd (now calledBonAlive Biomaterials, Ltd.)	SIGNIFICANTDIFFERENCES
Trade Name	BonAlive Granules	BonAlive Granules	None
510(k) Number	-	K071199
Product Code	MQV	MQV	None
Regulation Number	888.3045	888.3045	None
Regulation Name	Resorbable calcium saltbone void filler device	Resorbable calcium saltbone void filler device	None
Indications for Use	BonAlive® granules isindicated only for bonyvoids or gaps that are notintrinsic to the stability ofthe bony structure.BonAlive® granules isindicated to be gentlypacked into bony voids orgaps of the skeletal system(i.e. the extremities andpelvis). These defects maybe surgically createdosseous defects or osseousdefects created fromtraumatic injury to thebone. The productcontains a bone void fillerthat resorbs and isreplaced with bone duringthe healing process. Whenused in the extremities andpelvis, BonAlive® granulesis intended to be usedalone.	BonAlive® granules isindicated only for bonyvoids or gaps that are notintrinsic to the stability ofthe bony structure.BonAlive® granules isindicated to be gentlypacked into bony voids orgaps of the skeletal system(i.e. the extremities andpelvis). These defects maybe surgically createdosseous defects or osseousdefects created fromtraumatic injury to thebone. The product providesa bone void filler thatresorbs and is replacedwith bone during thehealing process. Whenused in the extremities andpelvis, BonAlive® granulesis intended to be usedalone. The device is notintended for use inposterolateral spineapplications.	None

Comparison of Characteristics

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Manufacturer	New Product	PREDICATE	SIGNIFICANT
Manufacturer	BonAlive Biomaterials, Ltd	Vivoxid Ltd (now calledBonAlive Biomaterials, Ltd.)	DIFFERENCES
Trade Name	BonAlive Granules	BonAlive Granules	None
		indicated for use in load-bearing applications,therefore, standardinternal or externalstabilization techniquesmust be followed to obtainrigid stabilization.
Rx or OTC	Rx	Rx	None
Physical Form	Amorphous, non-porousrandom-shaped particles	Amorphous, non-porousrandom-shaped particles	None
Color	Brown	Slightly pink	Color is different
MaterialsComposition	SiO2, Na2O, CaO and P2O5	SiO2, Na2O, CaO and P₂O5	None
	Granule sizes:0.5-0.8 mm1.0-2.0 mm	Granules sizes:0.5-0.8 mm1.0-2.02.0-3.15 mm	Largest granule size2.0-3.15 mm isobsolete
	Product volumes:1 cc2.5 cc5 cc10 cc	Product volumes:1 cc2 cc4 cc16 cc	Volumes aredifferent
Biocompatibility	BiocompatibleISO 10993	BiocompatibleISO 10993	None
Sterilization, SAL	GammaSterile, SAL 10-6	Dry HeatSterile, SAL 10-6	None
Pyrogenicity	Non-pyrogenic	Non-pyrogenic	None
Single Use/Reuse	Single use only	Single use only	None
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.	None
Properties	Synthetic	Synthetic	None

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

Manufacturer	New ProductBonAlive Biomaterials, Ltd	PREDICATEVivoxid Ltd (now calledBonAlive Biomaterials, Ltd.)	SIGNIFICANTDIFFERENCES
Trade Name	BonAlive Granules	BonAlive Granules	None
	Osteoconductive	Osteoconductive

9. Non-Clinical Performance Data

The following testing has been performed to support substantial equivalence to the predicate:

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

As part of demonstrating safety and effectiveness of BonAlive Granules, and in showing substantial equivalence to the predicate device, BonAlive completed a number of tests. The BonAlive Granules meets all the requirements for overall design and confirms that the output meets the design inputs and specifications. The BonAlive Granules passed all testing stated above as shown by the acceptable results obtained.

The BonAlive Granules complies with the applicable voluntary, national and international standards and guidance.

10. Biocompatibility

Biocompatibility testing was conducted in accordance with ISO-10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" The following biocompatibility studies were successfully performed with the BonAlive® granules: cytotoxicity, sensitization, systemic toxicity, and muscle implantation.

The granules predicate device was depyrogenated at 250 degrees Celsius for one hour prior to dry heat sterilization. Bacterial endotoxins were investigated in a LAL gel clot test. The analysis was performed according to Ph. Eur. 2.6.14 method A. The log reduction in endotoxin levels in the dry heat depyrogenation cycles was 4.6 logs. The results met USP requirement for bacterial endotoxins.

Similarly, as for the predicate device, a depyrogenation step at 250 degrees Celsius is performed for the granules subject device prior the gamma irradiation. The granules material and the depyrogenation method are the same for the predicate and the subject devices, thus the log reduction in the endotoxin levels for the predicate and the subject devices are equivalent. The testing performed on the predicate device supports the pyrogen status of the subject device. The predicate and subject devices are substantially equivalent in their nonpyrogenic nature.

{8}------------------------------------------------

11. Sterility and Shelf Life

The BonAlive Granules and Applicator (Granules) are sterilized with radiation. The sterility of the Granules was assured by using a validated sterilization method qualified in accordance with EN ISO 11137. After the sterilization cycle was completed, the Granules were placed on real-time shelf-life testing for a length of time to determine any degradation or loss of sterility over the anticipated shelf-life period of five (5) years. The validations and shelf life testing were completed successfully in accordance with ISO 11607.

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. These types of devices, including the predicate devices, have been on the market for many years with a proven safety and efficacy for the use of the device. The non-clinical testing detailed in this submission supports the substantial equivalence of the device.

13. Statement of Substantial Equivalence

A device is substantially equivalent to a predicate device when the device has the same intended use and the same technological characteristics as the previously cleared predicate device, and that the new device does not raise different questions regarding its safety and effectiveness as compared to the predicate device. BonAlive Granules is substantially equivalent to its predicate.

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.