The KHEIRON® Spinal Fixation System, including patient specific K-ROD, is intended to provide immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the following acute and chronic instabilities or deformities of thoracic, lumbar, and sacral spine: degenerative disc disease (defined as back pain of discogenic origin with degeneration of the disc confirmed by history and radiographic studies), degenerative spondylolisthesis with objective evidence of neurological impairment, fracture, deformities or curvatures (i.e. scoliosis, kyphosis, and/or lordosis), spinal tumor, pseudarthrosis and failed previous fusion. When used for posterior, non-cervical, pedicle screw fixation in pediatric patients, the KHEIRON® System including patient specific K-ROD is indicated as an adjunct to fusion to treat progressive spinal deformities (i.e., scoliosis, kyphosis, or lordosis) including idiopathic scoliosis, and congenital scoliosis. Additionally, the KHEIRON® Spinal Fixation System including patient specific K-ROD is intended to treat pediatric patients diagnosed with spondylolisthesis/spondylolysis, fracture caused by tumor and/or trauma, pseudarthrosis, and/or failed previous fusion.

This system is intended to be used with autograft and/or allograft.

Pediatric pedicle screw fixation is limited to a posterior approach.

Patient specific K-ROD devices are compatible with Nu Vasive Reline System components that are compatible with ø5.5mm and/or ø6.0mm rods as well as screws ø4.5mm or larger and at least 25mm in length.

Device Description

S.M.A.I.O.'s patient specific K-ROD is part of the 510(k) cleared KHEIRON® Spinal Fixation system (K211981) designed for stabilization and correction of chronic instability or deformity of the thoracic, lumbar, and sacral spine. The patient specific K-ROD is manufactured from Ti-6Al-4V ELI per ASTM F136 and is available in diameters of 5.5 and 6.0 mm.

The NuVasive Reline System is a 510(k) cleared pedicle screw system (K223181) that consists of a variety of screws, hooks, rods, lock screws, transverse connectors, rod-to-rod connectors, iliac connectors, and general instruments. Implant components are available in a variety of sizes and can be rigidly locked into a variety of different configurations to suit the individual pathology and anatomical conditions of the patient. The NuVasive Reline System is designed to provide immobilization and stabilization of spinal segments as an adjunct to fusion in the treatment of acute and chronic instabilities or deformities of the posterior thoracic, lumbar, and sacral spine. The NuVasive Reline System is also used to treat severe spondylolisthesis (Grades 3 and 4) of the L5-S1 vertebral joint in skeletally mature patients receiving fusion by autogenous bone graft.

The purpose of this Special 510(k) Device Modification is to extend indication of S.M.A.I.O.'s patient specific K-ROD (K211981) for use with the NuVasive Reline System (K223181).

AI/ML Overview

This FDA 510(k) clearance document is for a medical device modification, not an AI/Software as a Medical Device (SaMD) product. Therefore, many of the requested elements for describing an AI study, such as acceptance criteria based on performance metrics (e.g., sensitivity, specificity), sample sizes for test/training sets, expert ground truth establishment, MRMC studies, or standalone algorithm performance, are not applicable to this submission.

This submission focuses on demonstrating the substantial equivalence of a physical medical device modification (compatibility of a patient-specific K-ROD with another spinal fixation system) through engineering analysis and mechanical testing.

However, I can extract information related to the "acceptance criteria" and the "study" in the context of this physical device's mechanical performance:

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria (Mechanical Performance)	Reported Device Performance (Findings from V&V Activities)
K-ROD used with NuVasive Reline System must demonstrate similar strength to the primary predicate K-ROD.	K-ROD used with the NuVasive Reline System has similar strength as the primary predicate K-ROD.
Must pass Static and dynamic ASTM F1717 tests.	Tests were performed specifically for K-RODs used with the NuVasive Reline System, with identical set-up and parameters as presented in K211981 (primary predicate's clearance). (Implied passing, as concluded to be substantially equivalent).
Must pass Static torsion ASTM F1717 tests.	Tests were performed (Implied passing).
Must pass Static axial gripping capacity ASTM F1798 tests.	Tests were performed (Implied passing).
Must pass Static torsional gripping capacity ASTM F1798 tests.	Tests were performed (Implied passing).
Compatibility of patient-specific K-ROD with NuVasive Reline System components compatible with ø5.5mm and/or ø6.0mm rods, and screws ø4.5mm or larger and at least 25mm in length.	The information presented...demonstrates that the KHEIRON® Spinal Fixation System, including patient specific K-ROD, is compatible with the NuVasive Reline System as described herein.
No new worst-case scenario created for the K-ROD used with the NuVasive Reline System relative to the primary predicate K-ROD and predicate NuVasive Reline System devices.	Engineering analysis comparing K-ROD and NuVasive Reline System's titanium alloy rods determined that a new worst-case was not created.

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

Sample Size: Not explicitly stated as "sample size" in the context of a dataset for AI. For mechanical testing, a "sample size" would refer to the number of physical devices tested. This detail is not provided, but it would have been determined by the specific ASTM standards (F1717, F1798) and internal engineering justifications.
Data Provenance: This relates to the mechanical testing and engineering analysis performed for the modification. The tests were performed as part of the "V&V activities" (Verification & Validation) by the manufacturer S.M.A.I.O. (France). The data is prospective in the sense that the tests were conducted specifically for this submission.

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

Not Applicable. This is a physical device modification, not an AI/SaMD. "Ground truth" in this context would refer to established engineering principles, material science data, and the specifications of the predicate devices, which are handled by qualified engineers and technical personnel during the design and testing phases.

4. Adjudication method for the test set:

Not Applicable. This is a physical device submission. Adjudication methods like 2+1 or 3+1 are used for evaluating discrepancies in human expert interpretation, typically in AI/imaging studies.

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 is a physical device submission, not an AI/SaMD.

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

Not Applicable. This device is a physical medical implant, not an algorithm.

7. The type of ground truth used:

Engineering Standards and Predicate Device Specifications: The "ground truth" for this submission would be the established mechanical and material properties defined by ASTM standards (F136 for material, F1717 and F1798 for mechanical testing) and the known performance and characteristics of the legally marketed predicate devices (KHEIRON® Spinal Fixation System (K211981) and NuVasive Reline System (K223181)). The "acceptability" is based on meeting or demonstrating equivalence to these established benchmarks.

8. The sample size for the training set:

Not Applicable. This is a physical device submission, not an AI/SaMD. There is no concept of a "training set" in this context.

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

Not Applicable. See point 8.

Summary

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September 29, 2023

S.M.A.I.O. % Robert A. Poggie, Ph.D. President BioVera, Inc. 65 Promenade Saint Louis Notre Dame de l'Île Perrot, Quebec J7W3J6 Canada

Re: K232650

Trade/Device Name: KHEIRON® Spinal Fixation System, including patient specific K-ROD Regulation Number: 21 CFR 888.3070 Regulation Name: Thoracolumbosacral Pedicle Screw System Regulatory Class: Class II Product Code: NKB, KWP Dated: August 30, 2023 Received: August 31, 2023

Dear Dr. Poggie:

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.

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).

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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 OS 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.

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 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,

Brent Showalter -S

for Colin O'Neill, M.B.E. Assistant Director DHT6B: Division of Spinal Devices OHT6: Office of Orthopedic Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K232650

Device Name

KHEIRON® Spinal Fixation System, including patient specific K-ROD

Indications for Use (Describe)

This system is intended to be used with autograft and/or allograft.

Pediatric pedicle screw fixation is limited to a posterior approach.

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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Special 510(k) Device Modification, K232650 KHEIRON® Spinal Fixation System, including patient specific K-ROD

In accordance with 21 CFR 807.92 of the Federal Code of Regulations, the following is a summary of safety and effectiveness of the KHEIRON® Spinal Fixation System, including patient specific K-ROD, and compatibility with NuVasive's Reline System.

A. SUBMITTERS INFORMATION

Submitter Name:	BioVera, Inc.
Submitter Address:	65 Promenade Saint-Louis, NDIP, Québec, J7W3J6, CANADA
Contact Person:	Robert A. Poggie, PhD
Phone Number:	514-901-0796
Date of Submission:	August 30, 2023

B. DEVICE IDENTIFICATION & MANUFACTURER

Manufacturer Name:	S.M.A.I.O
Manufacturer Address:	2 place Berthe Morisot - Parc Technologique 69800 Saint Priest - FRANCE
Registration Number:	3015383864
Contact Name:	Jean-Charles ROUSSOULY
Title:	Vice-President Operations
Device Trade Name:	KHEIRON® Spinal Fixation System, including patient specific K-ROD
Regulation Name:	Thoracolumbosacral Pedicle Screw System
Regulation Number:	21 CFR sections 888.3070
Classification Codes:	Primary code: NKB Additional code: KWP
Classification Panel:	Orthopedic
C1. PRIMARY PREDICATE DEVICE
K211981	KHEIRON® Spinal Fixation System
C2. ADDITIONAL PREDICATE DEVICE
K223181	NuVasive Reline System

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D. DEVICE DESCRIPTION

The purpose of this Special 510(k) Device Modification is to extend indication of S.M.A.I.O.'s patient specific K-ROD (K211981) for use with the NuVasive Reline System (K223181).

E. INDICATIONS FOR USE

When used for posterior, non-cervical, pedicle screw fixation in pediatric patients, the KHEIRON® Spinal Fixation System including patient specific K-ROD is indicated as an adjunct to fusion to treat progressive spinal deformities (i.e., scoliosis, kyphosis, or lordosis) including idiopathic scoliosis, neuromuscular scoliosis, and congenital scoliosis. Additionally, the KHEIRON® Spinal Fixation System including patient specific K-ROD is intended to treat pediatric patients diagnosed with spondylolisthesis/spondylolysis, fracture caused by tumor and/or trauma, pseudarthrosis, and/or failed previous fusion.

This system is intended to be used with autograft and/or allograft.

Pediatric pedicle screw fixation is limited to a posterior approach.

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Patient specific K-ROD devices are compatible with NuVasive Reline System components that are compatible with ø5.5mm and/or ø6.0mm rods as well as screws ø4.5mm or larger and at least 25mm in length.

F. TECHNOLOGICAL CHARACTERISTICS, COMPARISON TO PREDICATE DEVICE

The patient specific K-ROD subject device is identical to the patient specific K-ROD cleared in K211981. The components of the NuVasive Reline System that interface with the patient specific K-ROD are identical to those cleared in K223181. The purpose of this Special 510(k) is to present the V&V activities demonstrating that the K-ROD can be used with the NuVasive Reline System.

Intended Use: K-RODs used in conjunction with the NuVasive Reline System, and the predicate devices are intended to be used to maintain spine shape until fusion occurs.

Indications for Use: The indications for use statement for the primary predicate and subject devices are the same.

Material: K-RODs used in conjunction with the NuVasive Reline System uses the same material as the predicates (ASTM F136 Ti-6AI-4V alloy).

Design: K-RODs used in conjunction with the NuVasive Reline System and the predicate devices are substantially equivalent in shape, sizes, material, and manufacturing process.

Strength: K-ROD used with the NuVasive Reline System has similar strength as the primary predicate K-ROD per verification and validation activities.

G. PERFORMANCE DATA

Engineering analysis and mechanical testing of K-RODs used with the NuVasive Reline System were performed to verify and validate the mechanical characteristics of the expanded use of patient specific K-RODs. The following mechanical tests were performed as part of the V&V activities:

Static and dynamic ASTM F1717 .
Static torsion ASTM F1717 ●
Static axial gripping capacity ASTM F1798 .
Static torsional gripping capacity ASTM F1798 ●

The ASTM F1717 and F1798 tests performed for V&V of K-ROD used with the NuVasive Reline System were identical in set-up and test parameters as presented in K211981. Engineering analysis comparing K-ROD and NuVasive Reline System's titanium alloy rods determined that a new worst-case was not created for the K-ROD used with the NuVasive Reline System relative to the primary predicate K-ROD and predicate NuVasive Reline System devices.

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H. CONCLUSIONS

The information presented in this Special 510(k) Device Modification demonstrates that the KHEIRON® Spinal Fixation System, including patient specific K-ROD, is compatible with the NuVasive Reline System as described herein and is therefore substantially equivalent to the legally marketed predicate devices.

Regulation Number and Section

§ 888.3070 Thoracolumbosacral pedicle screw system.

(a)
Identification. (1) Rigid pedicle screw systems are comprised of multiple components, made from a variety of materials that allow the surgeon to build an implant system to fit the patient's anatomical and physiological requirements. Such a spinal implant assembly consists of a combination of screws, longitudinal members (e.g., plates, rods including dual diameter rods, plate/rod combinations), transverse or cross connectors, and interconnection mechanisms (e.g., rod-to-rod connectors, offset connectors).(2) Semi-rigid systems are defined as systems that contain one or more of the following features (including but not limited to): Non-uniform longitudinal elements, or features that allow more motion or flexibility compared to rigid systems.
(b)
Classification. (1) Class II (special controls), when intended to provide immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the treatment of the following acute and chronic instabilities or deformities of the thoracic, lumbar, and sacral spine: severe spondylolisthesis (grades 3 and 4) of the L5-S1 vertebra; degenerative spondylolisthesis with objective evidence of neurologic impairment; fracture; dislocation; scoliosis; kyphosis; spinal tumor; and failed previous fusion (pseudarthrosis). These pedicle screw spinal systems must comply with the following special controls:(i) Compliance with material standards;
(ii) Compliance with mechanical testing standards;
(iii) Compliance with biocompatibility standards; and
(iv) Labeling that contains these two statements in addition to other appropriate labeling information:
“Warning: The safety and effectiveness of pedicle screw spinal systems have been established only for spinal conditions with significant mechanical instability or deformity requiring fusion with instrumentation. These conditions are significant mechanical instability or deformity of the thoracic, lumbar, and sacral spine secondary to severe spondylolisthesis (grades 3 and 4) of the L5-S1 vertebra, degenerative spondylolisthesis with objective evidence of neurologic impairment, fracture, dislocation, scoliosis, kyphosis, spinal tumor, and failed previous fusion (pseudarthrosis). The safety and effectiveness of these devices for any other conditions are unknown.”
“Precaution: The implantation of pedicle screw spinal systems should be performed only by experienced spinal surgeons with specific training in the use of this pedicle screw spinal system because this is a technically demanding procedure presenting a risk of serious injury to the patient.”
(2) Class II (special controls), when a rigid pedicle screw system is intended to provide immobilization and stabilization of spinal segments in the thoracic, lumbar, and sacral spine as an adjunct to fusion in the treatment of degenerative disc disease and spondylolisthesis other than either severe spondylolisthesis (grades 3 and 4) at L5-S1 or degenerative spondylolisthesis with objective evidence of neurologic impairment. These pedicle screw systems must comply with the following special controls:
(i) The design characteristics of the device, including engineering schematics, must ensure that the geometry and material composition are consistent with the intended use.
(ii) Non-clinical performance testing must demonstrate the mechanical function and durability of the implant.
(iii) Device components must be demonstrated to be biocompatible.
(iv) Validation testing must demonstrate the cleanliness and sterility of, or the ability to clean and sterilize, the device components and device-specific instruments.
(v) Labeling must include the following:
(A) A clear description of the technological features of the device including identification of device materials and the principles of device operation;
(B) Intended use and indications for use, including levels of fixation;
(C) Identification of magnetic resonance (MR) compatibility status;
(D) Cleaning and sterilization instructions for devices and instruments that are provided non-sterile to the end user; and
(E) Detailed instructions of each surgical step, including device removal.
(3) Class II (special controls), when a semi-rigid system is intended to provide immobilization and stabilization of spinal segments in the thoracic, lumbar, and sacral spine as an adjunct to fusion for any indication. In addition to complying with the special controls in paragraphs (b)(2)(i) through (v) of this section, these pedicle screw systems must comply with the following special controls:
(i) Demonstration that clinical performance characteristics of the device support the intended use of the product, including assessment of fusion compared to a clinically acceptable fusion rate.
(ii) Semi-rigid systems marketed prior to the effective date of this reclassification must submit an amendment to their previously cleared premarket notification (510(k)) demonstrating compliance with the special controls in paragraphs (b)(2)(i) through (v) and paragraph (b)(3)(i) of this section.