MagnetOs Flex Matrix is intended to fill bony voids or gaps of the skeletal system, i.e., posterolateral spine. In the posterolateral spine, MagnetOs Flex Matrix must be hydrated with bone marrow aspirate and used as an extender to autograft bone. The osseous defects may be surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure.

MagnetOs Flex Matrix resorbs and is replaced with bone during the healing process.

Device Description

MagnetOs Flex Matrix is a resorbable, osteoconductive bone void filler, intended to fill bony voids or gaps of the skeletal system, i.e., posterolateral spine, In the posterolateral spine, MagnetOs Flex Matrix must be hydrated with bone marrow aspirate and used as an extender to autograft bone. The product is biocompatible.

MaqnetQs Flex Matrix is a mixture of medical grade collagen and hydroxyapatite and ß-tricalcium phosphate ceramic granules. The collagen is produced from highly purified bioresorbable bovine split skin and consists mainly of collagen type I. The ceramic portion of MagnetOs Flex Matrix consists of β-tricalcium phosphate and hydroxyapatite.

MagnetOs Granules has a porous trabecular structure that resembles the structure and interconnected porosity of human cancellous bone. The surface of MagnetOs Granules is covered with needle-shaped features that are submicron in size.

The collagen matrix has a fibrillar porous structure which allows for the exposure of MagnetOs Granules' surface structure without interfering with its mode of action. While the collagen sponge matrix is readly resorbed in the first 6 weeks after implantation, MagnetOs Granules guides the three-dimensional regeneration of bone in the defect into which it is implanted. New bone will be deposited on the surface of the graft when it is placed next to viable host bone. The graft will be resorbed and replaced by bone during the natural process of bone remodelling.

MagnetOs Flex Matrix is a ready-to-use product. Upon hydration, the material is moldable and allows users to shape MagnetOs Flex Matrix to conform to the contours of bony defects. MagnetOs Flex Matrix is gamma-sterilized, sterile packaged and ready for single patient use only.

AI/ML Overview

The K213959 510(k) submission for MagnetOs Flex Matrix describes a resorbable calcium salt bone void filler. The submission focuses on demonstrating substantial equivalence to predicate devices through non-clinical testing and animal studies.

Here's the breakdown of the acceptance criteria and study details based on the provided text, with specific answers to your numbered points:

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

The provided text does not explicitly state quantitative acceptance criteria in a pass/fail format for specific performance metrics. Instead, the "acceptance criteria" are implied by the demonstration of substantial equivalence to predicate devices in the following areas:

Acceptance Criteria (Implied by Substantial Equivalence to Predicates)	Reported Device Performance (Summary)
Physicochemical and Crystallographic Characteristics	Bench-top testing confirmed that the MagnetOs Granules component in MagnetOs Flex Matrix is identical to the standalone MagnetOs Granules device. SEM and XRD confirmed the collagen matrix does not alter MagnetOs Granules specifications, ensuring its mode of action is not compromised.
Biocompatibility	Demonstrated through ISO 10993 testing and the long history of clinical use of collagen and calcium phosphate materials. Bacterial endotoxin testing (LAL method) showed the device meets established endotoxin limits.
Performance in Posterolateral Spine Fusion (as autograft extender)	Animal studies in a rabbit posterolateral spine fusion model demonstrated substantial equivalence in performance of MagnetOs Flex Matrix to the primary predicate device, MASTERGRAFT® Strip, as an autograft extender (1:1 volume ratio). Comparison with prior studies of MagnetOs Granules also confirmed substantial equivalence in performance. Evaluation endpoints included manual palpation, range of motion, radiography, micro-CT, undecalcified histology, and histomorphometric analysis.

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

Sample Size for Test Set: The text mentions "animals" were evaluated in the rabbit posterolateral spine fusion model but does not specify the exact number of animals used in the study for MagnetOs Flex Matrix. It states "Animals were evaluated after implantation...".
Data Provenance: The animal study was conducted using a rabbit posterolateral spine fusion model. The country of origin for the study is not specified in the document, but it's an animal study for pre-clinical performance testing. It is inherently prospective in its design as it involves implanting the device and then evaluating outcomes over time.

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

The document does not mention the use of human experts to establish ground truth in the context of the animal study. The evaluation endpoints were objective measures such as:

Manual palpation
Range of motion flexibility testing
Plain and high-resolution radiography
Microcomputed tomography (micro-CT) imaging
Undecalcified histologic evaluation
Histomorphometric analysis

The grading according to ISO 10993-6 (Annex E) for decalcified paraffin histology sections would typically be performed by trained histologists/pathologists, but the number and specific qualifications of such individuals are not detailed.

4. Adjudication method for the test set

The document does not describe an adjudication method (like 2+1 or 3+1) for the test set. Given that the ground truth was established through objective measurements and standard histological grading, an adjudication process involving multiple human readers for a "ground truth" establishment in a subjective interpretation sense is not indicated.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This submission is for a medical device (bone void filler), not an AI-based diagnostic or assistive technology. 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

This question is not applicable. The MagnetOs Flex Matrix is a physical medical device (bone void filler), not an algorithm or AI system.

7. The type of ground truth used

The ground truth for the animal study (performance test set) was established through a combination of:

Objective physiological assessments: Manual palpation, range of motion flexibility.
Imaging data: Plain and high-resolution radiography, micro-CT.
Histological and histomorphometric analysis: Microscopic evaluation of tissue samples, including grading according to ISO 10993-6 (Annex E).
Comparison to controls: Autograft (positive control) and primary predicate device (MASTERGRAFT® Strip).

This can be categorized as a combination of animal model outcomes data and expert histological/imaging interpretation (though the number of experts is not specified).

8. The sample size for the training set

This question is not applicable. This submission is for a physical medical device, not an AI/ML algorithm. There is no concept of a "training set" in the context of demonstrating substantial equivalence for a bone void filler through animal studies and bench testing.

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

This question is not applicable for the same reason as point 8.

Summary

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April 14, 2022

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Food and Drug Administration (FDA). On the left is the Department of Health and 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 square are the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Kuros Biosciences BV Sonja van der Meer Regulatory Affairs Expert Professor Bronkhorstlaan 10, Building 48 Bilthoven, 3723 MB, The Netherlands

Re: K213959

Trade/Device Name: MagnetOs Flex Matrix Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MQV Dated: March 9, 2022 Received: March 9, 2022

Dear Sonja van der Meer:

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 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

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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.

Laura C. Rose, 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) K213959

Device Name MagnetOs Flex Matrix

Indications for Use (Describe)

MagnetOs Flex Matrix resorbs and is replaced with bone during the healing process.

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)

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Kuros Biosciences Traditional 510(k) For MagnetOs Flex Matrix

510(k) Summary

This 510(k) Summary is submitted in accordance with 21 CFR Part 807, Section 807.92.

Submitter's Name:

Kuros Biosciences B.V.

Submitter's Address:

Kuros Biosciences B.V. Prof. Bronkhorstlaan 10, building 48 3723 MB Bilthoven The Netherlands

Establishment Registration Number:

3008147766

Contact Person:

Sonja van der Meer

Telephone +31 (0)30 229 7280

Date Prepared:

14th April 2022

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Kuros Biosciences Traditional 510(k) For MaqnetOs Flex Matrix

The Device Classification Information regarding MagnetOs Flex Matrix is summarized below.

Primary Product Code

RegulationNumber	Device	Device Class	Product Code	ClassificationPanel
888.3045	Resorbable calciumsalt bone void filler	2	MQV	Orthopedic

Device Trade Name

MaqnetOs Flex Matrix

Device Common Name

Resorbable calcium salt bone void filler

Device Description

Intended Use

MagnetOs Flex Matrix is intended to fill bony voids or gaps of the skeletal system, i.e., posterolateral spine. In the posterolateral spine, MagnetOs Flex Matrix must be hydrated with bone marrow aspirate and used as an extender to autograft bone. The osseous defects may be surgically created or the result of traumatic injury to the bone that are not intrinsic to the stability of the bony structure.

MagnetOs Flex Matrix resorbs and is replaced with bone during the healing process.

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Kuros Biosciences Traditional 510(k) For MaqnetOs Flex Matrix

Summary of Substantial Equivalence

MagnetOs Flex Matrix is substantially equivalent in indications and design principles to the following cleared and legally marketed predicate devices:

Table 1.1: Subject device and Predicate devices general information
Property	510(k) Subject Device	Primary PredicateDevice	Equivalent Device	Equivalent Device
Device Name	MagnetOs Flex Matrix	MASTERGRAFT® Strip	Vitoss Scaffold Foam	MagnetOs Granules
DeviceManufacturer	Kuros Biosciences B.V.	Medtronic SofamorDanek USA	Othovia, Inc	Kuros Biosciences B.V.
510(k)	No	K082166	K032288	K161859
DeviceClassification	II	II	II	II
Product Code	MQV	MQV	MQV	MQV
UseEnvironment	Medical / Clinical	Medical / Clinical	Medical / Clinical	Medical / Clinical
Anatomiclocation	Bony voids or gaps ofthe skeletal system, i.e.,posterolateral spine	Bony voids or gaps ofthe skeletal system, i.e.,the extremities, spineand pelvis	Bony voids or gaps ofthe skeletal system, i.e.,the extremities, spineand pelvis	Bony voids or gaps ofthe skeletal system, i.e.,posterolateral spine
Materials	hydroxyapatite and β-tricalcium phosphatemixture	hydroxyapatite and β-tricalcium phosphatemixture	β-tricalcium phosphatemixture	hydroxyapatite and β-tricalcium phosphatemixture
	Bovine collagen type I	Bovine collagen type I	Bovine collagen type I	-
Dosage form	Strips	Strips	Strips	Granules

Table 1 1: Subjoct dovice and Prodicato dovices gonoral information

MaqnetQs Flex Matrix is substantially equivalent to the predicate device MASTERGRAFT® Strip and to equivalent devices Vitoss Foam and MagnetOs Granules with respect to design, structure, materials, and mechanism of action, and has similar Indications for Use.

For the two MagnetOs devices, the MagnetOs Granules component is identical.

MASTERGRAFT® Strip is the primary predicate device used for animal performance testing studies. MagnetOs Granules is the reference standard comparators used for comparison animal studies.

Non-clinical Testing (Performance/Physical Data):

Characterization of MagnetOs Flex Matrix materials has been conducted in compliance with the Guidance for Industry and FDA Staff – Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device (Document issued on: June 2, 2003) and the requirements of other applicable standards.

Bench-top testing was performed to evaluate the physicochemical and crystallographic characteristics of MaqnetOs Flex Matrix, which demonstrated that the MagnetOs Granules component in MagnetOs Flex Matrix is identical to MagnetOs Granules device. With SEM and XRD it is confirmed that the collagen matrix does not change the MagnetOs Granules specifications. This ensures that the mode of action is not compromised.

Biocompatibility testing:

The biocompatibility of the MaqnetOs Flex Matrix is demonstrated by ISO 10993 testing and the long history of clinical use of the collagen and calcium phosphate materials for the same intended use.

Bacterial endotoxin testing was performed using the limulus amebocyte lysate (LAL) method and showed that the device meets the endotoxin limits of established guidelines.

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Kuros Biosciences Traditional 510(k) For MaqnetOs Flex Matrix

Animal studies:

Substantial equivalence in performance of MagnetOs Flex Matrix to Mastergraft Strip was provided by in vivo animal data in the intended use.

Mastergraft Strip is the primary predicate device used for animal performance testing studies. The performance of the MagnetOs Flex Matrix was established in a posterolateral spine fusion animal model that justifies that MagnetOs Flex Matrix can be used as an autograft extender (1:1 volume ratio) in posterolateral spine.

Animal testing was performed in a rabbit posterolateral spine fusion model to demonstrate substantial equivalence to the primary predicate device. Animals were evaluated after implantation with the subject device, the primary predicate device, and autograft (positive control) up to 12 weeks. Evaluation endpoints included manual palpation, range of motionflexibility testing, plain and high-resolution radiography, microcomputed tomography (micro-CT) imaging, undecalcified histologic evaluation, and histomorphometric analysis. Decalcified paraffin histology sections also were graded according to ISO 10993-6 (Annex E).

The exact same animal model and study design were used for pre-clinical performance testing of MagnetQs Granules (K161859, K21311). By comparing the outcomes of both studies, substantial equivalence in performance of MagnetOs Flex Matrix and MagnetOs Granules is confirmed.

From all available pre-clinical data, it is concluded that the performance of MagnetOs Flex Matrix is substantially equivalent to both the primary predicate device, Mastergraft Strip, and MagnetOs Granules.

Safety and Effectiveness/Conclusion:

Based on the information presented in these 510(k) premarket notifications, MagnetOs Flex Matrix is considered substantially equivalent to predicate devices. It is our determination that MagnetOs Flex Matrix is as safe and effective as currently marketed predicate devices.

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.