GlassBone 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. GlassBone Granules resorbs and is replaced with bone during the healing process.

Device Description

GlassBone Granules is a synthetic and biocompatible bone substitute device (bioactive glass 4555). GlassBone Granules is composed by weight of 4555 bioactive glass granules (45% SiO2, 6% P2O5, 24.5% CaO and 24.5% Na2O). It is sterilized with gamma irradiation and is single use and is available in different unit sizes.

AI/ML Overview

The provided text describes the 510(k) premarket notification for "GlassBone Granules," a resorbable calcium salt bone void filler device. It focuses on demonstrating substantial equivalence to a predicate device, rather than proving the device meets specific performance criteria through a study with the detailed elements requested.

Therefore, I cannot provide a table of acceptance criteria and reported device performance, nor details about sample sizes, ground truth establishment, expert involvement, or comparative effectiveness studies (MRMC) as these are not present in the provided document.

The document states:

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

This means that the FDA's clearance for GlassBone Granules was based on its substantial equivalence to an already legally marketed predicate device (BonAlive Granules - K231528) and a reference device (NovaBone Resorbable Bone Graft Substitute - K052494), rather than a clinical study with new performance data.

Instead of a clinical study proving performance against acceptance criteria, the submission relied on non-clinical performance data (bench testing, animal testing, biocompatibility, sterility, and shelf life) to demonstrate that the device is as safe and effective as the predicate.

Here's a breakdown of what is in the document regarding the "study" that proves the device meets requirements, interpreted in the context of a 510(k) submission focused on substantial equivalence:

1. Table of "Acceptance Criteria" and "Reported Device Performance":
Not applicable in the traditional sense of a clinical trial for a standalone AI/software product, or a device requiring specific performance metrics against a disease state. The "acceptance criteria" here are implied by the standards and guidance documents followed to demonstrate equivalence.

"Acceptance Criteria" (Implied by Standards/Guidance)	Reported Device Performance (Summary from Non-Clinical Data)
Material Properties:
pH compatibility (ASTM F1538)	Bench testing conducted according to ASTM F1538; "acceptable results obtained."
Solubility (ASTM F1538)	Bench testing conducted according to ASTM F1538; "acceptable results obtained."
Apatite formation (ASTM F1538)	Bench testing conducted according to ASTM F1538; "acceptable results obtained."
Composition (Heavy Metals, etc.) (ASTM F1538)	Bench testing conducted according to ASTM F1538; "acceptable results obtained."
Crystallinity (ASTM F1538)	Bench testing conducted according to ASTM F1538; "acceptable results obtained."
Particle Size (ASTM F1538)	Bench testing conducted according to ASTM F1538; "acceptable results obtained."
Surface Area (ASTM F1538)	Bench testing conducted according to ASTM F1538; "acceptable results obtained."
Biocompatibility: (ISO-10993-1)
Physico-chemical characterization	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility.
Cytotoxicity	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility.
Sensitization	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility.
Irritation/intracutaneous reactivity	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility.
Material mediated pyrogenicity	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility. Also noted "Non-pyrogenic" in comparison table.
Acute systemic toxicity	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility.
Local effects of implantation	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility.
Genotoxicity	Biocompatibility conducted per ISO-10993-1; results indicate biocompatibility.
Sterility: (ISO 11137 Radiation, ISO 11607 Packaging)
Sterility Assurance Level (SAL 10⁻⁶)	ISO 11137 Radiation Sterilization Validation performed and successful.
Packaging integrity for terminally sterilized medical devices	ISO 11607 Packaging validation performed and successful.
Shelf Life:	Determined as acceptable based on unspecified testing details.
Overall Design: ("output meets design inputs and specifications")	"GlassBone Granules meet all requirements for overall design and confirms that the output meets the design inputs and specifications. The GlassBone Granules passed all testing stated above as shown by acceptable results obtained." This is a general statement summarizing the success of all non-clinical tests.

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

Sample size for test set: Not applicable as no clinical test set was used for a performance study. Non-clinical bench and animal testing typically use specific quantities of samples as per ASTM and ISO standards, but these details are not provided here.
Data provenance: Not applicable for a clinical test set. The non-clinical data would have been generated in labs as part of the device development and validation.

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

Not applicable as no clinical test set with human ground truth (e.g., image annotation) was established. The ground truth for non-clinical tests is based on objective measurements and established scientific methods (e.g., chemical analysis, microbiological assays).

4. Adjudication method for the test set:

Not applicable as no clinical test set requiring human adjudication was used.

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 device is a physical bone void filler, not an AI software. No MRMC study was conducted.

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

Not applicable. This is not an algorithm/software device.

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

For the non-clinical tests, the "ground truth" is based on the objective measurements and scientific standards applied in the bench (e.g., chemical composition analysis, particle size distribution) and animal (e.g., histological analysis of tissue response, biocompatibility markers) studies. There is no "ground truth" in the sense of clinical annotations or outcomes data from a patient cohort.

8. The sample size for the training set:

Not applicable. This is not an AI/machine learning device that requires a training set.

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

Not applicable.

In summary, the FDA document indicates that the "GlassBone Granules" device's safety and effectiveness were demonstrated through a comparison to a legally marketed predicate device and through robust non-clinical (bench and animal) testing that confirmed its material properties, biocompatibility, sterility, and shelf life, showing it performs comparably to established devices. No clinical studies or AI-specific performance evaluations were deemed necessary or conducted for this 510(k) submission.

Summary

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

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.

December 23, 2024

Noraker % Elisa Maldonado-Holmertz RA/QA Consultant Obelix Consulting 806 Jefferson Street Bastrop, Texas 78602

Re: K242782

Trade/Device Name: GlassBone Granules Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MQV Dated: November 12, 2024 Received: November 13, 2024

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 (the 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 available 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}------------------------------------------------

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-regulatory

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

assistance/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,

Digitally signed by JESSE MUIR JESSE MUIR -S Date: 2024.12.23 09:42:12 -05'00

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

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

Indications for Use

Submission Number (if known)

K242782

Device Name

GlassBone Granules

Indications for Use (Describe)

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

Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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."

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

510(k) SUMMARY

SUBMITTER

Submission Sponsor:

Catherine FLACARD Compliance & Innovation Chief Officer Noraker, SAS 60, Avenue Rockefeller 69008 Lyon France Email: c.flacard@noraker.com Tel number: +33 (0)4 78 93 30 92

Submission Correspondent:

Elisa Maldonado-Holmertz RA/QA Consultant Obelix Consulting, LLC 806 Jefferson St Bastrop, TX 78602 USA Email: elisamh@obelixconsult.com Tel number: +1 512 431 6069

Date Prepared: 13 September 2024

SUBJECT DEVICE

Name of Device: GlassBone Granules Common or Usual Name: Filler, Bone Void, Calcium Compound Classification Name: Resorbable calcium salt bone void filler device (21 CFR 888.3045) Regulatory Class: Class II Product Code: MQV

PREDICATE DEVICE

BonAlive Granules - K231528

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

This predicate has not been subject to a design-related recall.

REFERENCE DEVICE

NovaBone Resorbable Bone Graft Substitute - K052494 This predicate has not been subject to a design-related recall.

DEVICE DESCRIPTION

It is sterilized with gamma irradiation and is single use and is available in different unit sizes.

INDICATIONS FOR USE

Rx only.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

GlassBone Granules is substantially equivalent to the following predicate and reference device:

Manufacturer	Subject DeviceNoraker SAS	Primary predicateBonAlive Biomaterials, Ltd	Reference DeviceNovaBone	SIGNIFICANTDIFFERENCES
Trade Name	GlassBone® Granules	BonAlive® Granules	Resorbable Bone Graft Substitute(Particulate)	None
510(k) Number	-	K231528	K052494	-
Product Code	MQV	MQV	MQV	None
RegulationNumber	888.3045	888.3045	888.3045	None
Regulation Name	Resorbable calcium salt bone voidfiller device	Resorbable calcium salt bone voidfiller device	Resorbable calcium salt bone voidfiller device	None
Indications forUse	GlassBone Granules is an implantintended to fill bony voids or gaps ofthe skeletal system (i.e., extremities	Bonalive® Orthopedics granules is animplant intended to fill bony voids orgaps of the skeletal system (i.e.,	NovaBone Resorbable Bone graftsubstitute is indicated only for bony	None
Manufacturer	Subject DeviceNoraker SAS	Primary predicateBonAlive Biomaterials, Ltd	Reference DeviceNovaBone	SIGNIFICANTDIFFERENCES
Trade Name	GlassBone® Granules	BonAlive® Granules	Resorbable Bone Graft Substitute(Particulate)	None
	and pelvis). These osseous defectsmay be the result of benign bonecysts and tumors (in adults andpediatric patients ≥ 6years old), are surgically created orthe result of traumatic injury to thebone and are not intrinsic to thestability of thebony structure. GlassBone Granulesresorbs and is replaced with boneduring the healing process.	extremitiesand pelvis). These osseous defectsmay be the result of benign bonecysts and tumors (in adults andpediatric patients ≥ 6years old), are surgically created orthe result of traumatic injury to thebone and are not intrinsic to thestability of thebony structure. Bonalive®Orthopedics granules resorbs and isreplaced with bone during the healingprocess.	voids or gaps that are not intrinsic tothe stability of the bony structure.NovaBone is indicated to be gentlypacked into bony voids or gaps of theskeletal system (i.e. the extremities,spine and pelvis).These defects may be surgicallycreated osseous defects or osseousdefects created from traumatic injuryto the bone. The product provides abone void filler that resorbs and isreplaced with bone during the healingprocess.
Rx or OTC	Rx	Rx	Rx	None
Physical Form	Amorphous, non-porous random-shaped particles	Amorphous, non-porous random-shaped particles	Amorphous, non-porous random-shaped particles	None
Color	Brown	Brown	White	None
MaterialsComposition	Bioactive glass45S5 Bioglass (SiO₂, P₂O₅, CaO andNa₂O)	Bioactive glassS53P4 glass (SiO₂, P₂O₅, CaO andNa₂O)	Bioactive glass45S5 Bioglass (SiO₂, P₂O₅, CaO andNa₂O)	None
Product Sizes	Granule sizes:0.5-1mm1-3mmProduct volumes:0.5cc1 cc5 cc10 cc16 cc	Granule sizes:0.5-0.8 mm1.0-2.0 mmProduct volumes:1 cc2.5 cc5 cc10 cc	Granule sizes:90-710μmProduct volumes:2 cc5 cc10 cc15 cc	Similar withoutaffecting safety oreffectiveness
Biocompatibility	BiocompatibleISO 10993	BiocompatibleISO 10993	BiocompatibleISO 10993	None
Sterilization	Gamma, SAL 10⁻⁶	Gamma, SAL 10⁻⁶	EtO, SAL 10⁻⁶	None
Pyrogenicity	Non-pyrogenic	Non-pyrogenic	Non-pyrogenic	None
Single Use/Reuse	Single use only	Single use only	Single use only	None
Mode of action	Works by leaching ions that reactwith the body fluids transforming theglass surface chemically into one thatby its chemical composition andstructure resembles the mineralphase found in natural bone.	Works by leaching ions that reactwith the body fluids transforming theglass surface chemically into one thatby its chemical composition andstructure resembles the mineralphase found in natural bone.	Works by leaching ions that reactwith the body fluids transforming theglass surface chemically into one thatby its chemical composition andstructure resembles the mineralphase found in natural bone.	None
Manufacturer	Subject DeviceNoraker SAS	Primary predicateBonAlive Biomaterials, Ltd	Reference DeviceNovaBone	SIGNIFICANTDIFFERENCES
Trade Name	GlassBone® Granules	BonAlive® Granules	Resorbable Bone Graft Substitute(Particulate)	None
Properties	SyntheticOsteoconductive	SyntheticOsteoconductive	SyntheticOsteoconductive	None
MR safety	MR Safe	MR Safe	Unknown	None

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

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

NON CLINICAL PERFORMANCE DATA

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

Bench testing:

Bench testing was conducted according to FDA Guidance "Resorbable Calcium Salt Bone Void Filler Device - Class II Special Controls Guidance Document for Industry and FDA Staff" and ASTM F1538.

. pH
Solubility .
Apatite
Composition - Heavy Metals
Crystallinity
Particle Size
. Surface Area

Animal testing and 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".

Physico-chemical characterization
Cytotoxicity
Sensitization
Irritation or intracutaneous reactivity
Material mediated pyrogenicity
Acute systemic toxicity
Local effects of implantation
Genotoxicity

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

Sterility and Shelf Life

The following testing was performed on GlassBone Granules:

ISO 11137 Radiation Sterilization Validation ●
ISO 11607 Packaging for terminally sterilized medical devices ●

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.

Statement of Substantial Equivalence

Noraker GlassBone Granules is substantially equivalent to the predicate device when comparing the following characteristics:

•Indications for Use
•Principles of Use
•Fundamental Technology
•Basic Design
•Materials Used
•Where used
•Standards met
•Sterilization Method

GlassBone Granules meet all requirements for overall design and confirms that the output meets the design inputs and specifications. The GlassBone Granules passed all testing stated above as shown by acceptable results obtained.

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

Noraker, SAS believes that the bench and non-clinical performance data supports the safety of GlassBone Granules, and the device should perform effectively as intended in the specified use conditions. The non-clinical performance data demonstrates that GlassBone Granules performs comparably to the predicate device that is currently marketed for the same intended use and presents no new concerns about safety and effectiveness.

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.