The indications for use are biopsy of intracranial lesions, placement of stereoelectroencephalography (SEEG) electrodes and placement of anchor bolts for laser interstitial thermal therapy (LITT).

Device Description

The subject device Alignment System Cranial is an image guided surgery system intended to support the surgeon to plan and to achieve a trajectory with surgical instruments during cranial stereotactic procedures using optical tracking technology.

For this purpose, the Alignment System Cranial consists of a combination of hardware and software. The Alignment Software Cranial with LITT 2.1 is installed on an Image Guided Surgery (IGS) platform (Curve, Curve Navigation 17700, Kick 2 Navigation Station or Buzz Navigation) consisting of a computer unit, a touch display and an infrared tracking camera. During surgery, the software tracks the position of instruments in relation to the patient anatomy and identifies this position on pre- or intraoperative images. The position of the surgical instruments is continuously updated on these images by optical tracking. This position information is used by the software to align either passive or active positioning devices to a planned trajectory for subsequent surgical steps.

The Alignment System Cranial has different configurations of hardware devices depending on which positioning device is used and which indication is performed. The Alignment Software Cranial with LITT 2.1 supports the active positioning devices Surgical Base System 1.4 and Cirq Arm System 2.0 (+ Cirq Robotic Alignment Module + Cirq Robotic Disposable Kinematic Unit) as well as the passive positioning device VarioGuide. Both types of positioning devices consist of articulated arms with different joints where additional devices and surgical instruments can be attached to for further manual or robotic alignment to a defined trajectory.

In addition, the subject device offers a set of indication specific instruments to support biopsy, sEEG and LITT procedures. This instrumentation consists of instrument holders, tracking arrays, guide tubes, reduction tube, bone anchors, drill bits and depth stops. None of the instruments is delivered sterile. All patient contacting materials consist of different alloys of stainless steel.

The Alignment Software Cranial with LITT has the following accessories:

Automatic Registration providing an automatic registration for subsequent use.
Automatic Registration iMRI providing an automatic image registration for intraoperatively . acquired MR images.

AI/ML Overview

The provided text is a 510(k) summary for the "Alignment System Cranial," which includes "Alignment Software Cranial with LITT." It details the device's indications for use, description, and comparison to predicate devices, along with performance data to demonstrate substantial equivalence.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

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

Acceptance Criteria	Reported Device Performance	Meets Criteria?
Mean Positional Error (instrument tip) ≤ 2 mm	Mean Positional Error: 1.19 mm	Yes
Mean Angular Error (instrument axis) ≤ 2°	Mean Angular Error: 0.86°	Yes

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

Sample Size for Test Set:
- Number of registrations: 6
- Total number of samples: 37 (This likely refers to individual measurements taken over the 6 registrations)
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. However, the study was conducted as "System accuracy testing" to evaluate the device in "a realistic clinical setup and representative worst case scenarios," suggesting it was a controlled, prospective study performed by the manufacturer.

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

The document does not provide information on the number of experts or their qualifications used to establish ground truth for this system accuracy testing. This type of testing typically relies on metrology standards and physical measurements rather than clinical expert consensus for ground truth.

4. Adjudication method for the test set

The document does not specify an adjudication method. For system accuracy testing based on physical measurements, an adjudication process involving human experts is generally not applicable in the same way it would be for image-reading or diagnostic AI.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and its effect size

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. The performance data presented is for the system accuracy of the device concerning its ability to align instruments, not for a diagnostic AI algorithm that human readers would interact with. The document explicitly states: "No clinical testing was needed for the Subject Device since optical tracking technology in the scope of image guided surgery for the included indications for use is well established in the market."

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

The performance study was for the system's accuracy (hardware + software components), which is a key aspect of its standalone functionality in terms of guiding instruments. While it's not an "algorithm only" study in the sense of a pure AI diagnostic tool, it measures the precision of the device's output without direct human interpretation in the loop of the measurement itself. The "Automatic Registration" features (including one for iMRI) are mentioned as accessories, implying an algorithmic component, but specific performance criteria for these AI/ML-based features are not detailed beyond the general system accuracy. The document mentions that "There have been no changes to the AI/ML algorithm" for surface matching for patient registration, implying its prior validation.

7. The type of ground truth used

The ground truth for the system accuracy testing ("positional and angular navigation accuracy") would have been established through precise physical measurements using calibrated instruments and metrological standards (e.g., a coordinate measuring machine or similar setup to establish a true target position against which the device's reported position is compared). It is not based on expert consensus, pathology, or outcomes data, as this is a measurement of mechanical and software precision.

8. The sample size for the training set

The document does not provide information on the sample size for the training set for any embedded AI/ML components (e.g., the AI/ML based model for landmark delivery in surface matching). The focus of this 510(k) summary is on the system accuracy for the LITT indication, and asserts "no changes to the AI/ML algorithm" for patient registration.

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

The document does not provide information on how the ground truth for any training set was established for embedded AI/ML components. It only mentions that an existing AI/ML algorithm for surface matching landmarks has not changed.

Summary

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January 28, 2025

Brainlab AG Esther Moreno Garcia Manager Regulatory Affairs Olof-Palme Str.9 Munich, 81829 Germany

Re: K243698

Trade/Device Name: Alignment System Cranial, with Alignment Software Cranial with LITT; Circ Alignment Software Cranial Biopsy; Cirq Alignment Software Cranial sEEG: VarioGuide Alignment Software Cranial; Cirq Alignment Software Cranial LITT Regulation Number: 21 CFR 882.4560 Regulation Name: Stereotaxic Instrument Regulatory Class: Class II Product Code: HAW Dated: November 29, 2024 Received: November 29, 2024

Dear Esther Moreno Garcia:

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 (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.

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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 (OS) 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 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-regulatory

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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 Adam D. by Adam D. Pierce -S Pierce -S Date: 2025.01.28 17:39:20 -05'00' Adam D. Pierce, Ph.D. Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional, and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine 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) K243698

Device Name

Alignment System Cranial, with Alignment Software Cranial with LITT; Cirq Alignment Software Cranial Biopsy; Cirq Alignment Software Cranial sEEG;

Indications for Use (Describe)

Alignment System Cranial is intended to plan and to achieve a trajectory with surgical instruments during cranial stereotactic procedures.

The indications for use are biopsy of intracranial lesions, placement of stereoelectroencephalography (SEEG) electrodes and placement of anchor bolts for laser interstitial thermal therapy (LITT).

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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510(k) Summary

January 28th, 2025

General Information
Manufacturer	Brainlab AG; Olof-Palme-Str.9, 81829, Munich, Germany
Establishment Registration	8043933
Trade Name	Alignment System Cranial, with Alignment Software Cranial with LITTCirq Alignment Software Cranial BiopsyCirq Alignment Software Cranial sEEGVarioGuide Alignment Software CranialCirq Alignment Software Cranial LITT
Classification Name	Neurological Stereotaxic Instrument
Product Code	HAW
Regulation Number	882.4560
Regulatory Class	Class II
Panel	Neurology
Predicate Device(s)	Primary Predicate: K191597 Stealth Autoguide SystemSecondary Predicate: K223864 Alignment System Cranial
Contact Information
Primary Contact	Alternate Contact
Esther Moreno GarciaManager Regulatory AffairsPhone: +49 89 99 15 68 0Email: regulatory.affairs@brainlab.com	Chiara CunicoSenior Manager Regulatory AffairsPhone: +49 89 99 15 68 0Email: chiara.cunico@brainlab.com

1. Indication for Use

Alignment System Cranial is intended to plan and to achieve a trajectory with surgical instruments during cranial stereotactic procedures.

The indications for use are biopsy of intracranial lesions, placement of stereoelectroencephalography (SEEG) electrodes and placement of anchor bolts for laser interstitial thermal therapy (LITT).

2. Device Description

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The Alignment Software Cranial with LITT has the following accessories:

Automatic Registration providing an automatic registration for subsequent use. ●
Automatic Registration iMRI providing an automatic image registration for intraoperatively . acquired MR images.

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3. Substantial Equivalence

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

Characteristic	Primary PredicateK191597	Secondary Predicate K223864	Subject device
Indications for use	The Stealth Autoguide System is apositioning and guidance systemintended for the spatial positioning andorientation of instrument holders ortool guides to be used byneurosurgeons to guide standardneurosurgical instruments, based on apre-operative plan and feedback froman image-guided navigation systemwith three-dimensional imagingsoftware.The Stealth Autoguide System is aremotely-operated positioning andguidance system, indicated for anyneurological condition in which the useof stereotactic surgery may beappropriate (for example, stereotacticbiopsy, stereotactic EEG, laser tissueablation, etc.).	Alignment System Cranial is intended tosupport the surgeon to plan and toachieve a trajectory with surgicalinstruments during cranial stereotacticprocedures.The indications for use are biopsy ofintracranial lesions and placement ofstereoelectroencephalography(SEEG) electrodes.	Alignment System Cranial is intended toplan and toachieve a trajectory with surgicalinstruments during cranial stereotacticprocedures.The indications for use arebiopsy of intracranial lesions,placement ofstereoelectroencephalography (SEEG)electrodes and placement of anchorbolts for laser interstitial thermaltherapy (LITT).New indication LITT is equivalent toprimary predicate, biopsy and SEEG areequivalent to both predicates.
Localization technique	Optical markers on tool holder	Infrared tracking camera is recognizinginfrared passive markersInstrument tracking in relation to thepatients anatomy.	Same as both predicates
System accuracy	Under representative worst caseconfiguration: Mean navigationaccuracy of $\pm$ 2 mm and angular axisdisplacement of $\pm$ 2°	Under representative worst caseconfiguration: Mean navigationaccuracy of $\pm$ 2 mm and angular axisdisplacement of $\pm$ 2°	Same as both predicates
Operating principle	Preoperative images (StealthStation)Surgical planning (StealthStation)Patient registrationGuidance of instrumentsTrajectory alignment	Preoperative imagesSurgical planningPatient registrationGuidance of instrumentsTrajectory alignment with Cirq ArmSystem plus Cirq Robotic AlignmentModule or with the Varioguide	Same as secondary predicate andsimilar to primary predicate.
Planning software	Compatible with:S8 Cranial v1.1Synergy Cranial v.3.1	Compatible with:Cranial 3.1Trajectory Planning 2.5 and 2.6	Similar to secondary predicate. TheCranial 3.1 software is no longerneeded as the Subject Device includes anew component Cranial InstrumentSetup 3.0, providing the features forinstrument handling.
AlignmentInstrumentation	Navigated Trajectory GuideTool Holders (Drill Guides, ReducingTubes)Height GuidesTapping Tube	Alignment Guide TubesInstrument Holders, Tracking ArraysCranial Drill Bits + Depth StopsBone Anchors(for biopsy and sEEG)	Similar to both predicatesAlignment instrumentation is generallyused in all devices with a combinationof holders, guides and tubes. Comparedto secondary predicate,instrumentation has been extended tosupport new LITT indication.
Instrument fixation	Special tool holders for differentapplications mounted to the StealthAutoGuide	With Cirq Arm System: Cirq RoboticDisposable Kinematic Unit to which theinstrument holder is attached.	Mechanical connection is used in alldevices for instrument fixation.Identical to secondary predicate.
		With Varioguide: Different Disc sets aremechanically connected depending onguiding diameter.
Alignment process	Fine alignment robotically performedby Autoguide	With Cirq Arm System:-Rough alignment:Manual positioning of Cirq Arm Systemwith Autopilot feature (AlignmentSoftware) close to final position-Fine alignment:Robotic movement of Cirq RoboticAlignment ModuleWith Varioguide:Rough and fine alignment by manualpositioning of VarioGuide alongplanned trajectory with Autopilotfeature (Cranial Navigation)	Similar alignment process as Predicate1 and identical to Predicates 2.
Patient Registration	Optical Registration Device (via StealthStation)	Optical registration done withRegistration 3.6.Methods: Surface matching andlandmark registrationSurface matching: Landmarks (used forpre-registration) are delivered by anAI/ML based model.	Same registration methods as insecondary predicate. There have beenno changes to the AI/ML algorithm.
IGS Platforms	StealthStation surgical navigationplatform consisting of computer, touchmonitor and stereotactic camera.	Curve, Curve Navigation, Kick and BuzzNavigation models are used, consistingof computer, touch monitor and IRcamera.	Similar to predicates. A new platformmodel (Curve Navigation 17700#17701) was released but with overallsame components and operatingprinciple.

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4. Performance Data

The following testing was conducted on the Subject Device to establish substantial equivalence with the predicate devices:

Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Device Software Functions". These include successful implementation of product specifications, incremental testing for different release candidates, testing of risk control measures, compatibility testing or cybersecurity tests. The documentation level for this software is enhanced.

Usability Evaluation

Formative usability was carried out according to the standard IEC 62366-1 "Medical devices – Part 1: Application of usability engineering to medical devices" in a simulated clinical environment to validate the LITT workflow with the Cirq Arm System positioning device. This covered aspects such as the quidance provided by the software, the assembly of the arm, handling of different instruments, etc. with focus on the main differences implemented for LITT. The results confirmed that the LITT workflow is comparable in terms of user interaction to the biopsy and SEEG workflows, already present in the secondary predicate.

System accuracy testing

The positional and angular navigation accuracy for placement of anchor bolts in LITT procedures of the Subject Device including the software, the platforms and the instruments was evaluated considering a realistic clinical setup and representative worst case scenarios.

N ofregistrations	Total Nofsamples	Error Type	MeanError	SD	95th perc.	99th perc	99%upper CI
6	37	Positional [mm]	1.19	0.50	1.83	1.90	1.40
		Angular [°]	0.86	0.39	1.52	1.57	1.03

The above results show the following acceptance criteria are fulfilled:

Mean Positional Error of the placed instrument's tip ≤ 2 mm
Mean Anqular Error of the placed instrument's axis ≤ 2º

Therefore, the Subject Device achieves the same accuracy performance as both predicate devices.

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Electrical safety and electromagnetic compatibility (EMC)

Compliance to electrical safety, RFID and EMC was evaluated on the Subject device according to the standards: IEC 60601-1, AIM 7351731 and IEC 60601-1-2. The tests have shown that the subject device performs as intended.

Instruments

. Biocompatibility assessment acc. ISO 10993-1 considered the materials used in the devices, manufacturing process, processing, bioloqical and chemical test data, and the history of safety and effectiveness of the device materials in contact with the human body.
. Cleaning, disinfection and sterilization was carried out for instruments and sterilization trays considering the FDA guidance "Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling".
Mechanical properties of instruments were assessed by performing life cycle simulations and verification of clearance fits, material fatigue, functionality, etc.

No clinical testing was needed for the Subject Device since optical tracking technology in the scope of image guided surgery for the included indications for use is well established in the market.

5. Conclusion

The comparison of the Subject Device with the predicate devices shows that the Alignment System Cranial, with Alignment Software Cranial with LITT has similar functionality, intended use and technological characteristics as the predicate devices. Based on the comparison to the predicates and the performance testing conducted, the Subject Device is considered substantially equivalent to the predicate devices.

Regulation Number and Section

§ 882.4560 Stereotaxic instrument.

(a)
Identification. A stereotaxic instrument is a device consisting of a rigid frame with a calibrated guide mechanism for precisely positioning probes or other devices within a patient's brain, spinal cord, or other part of the nervous system.(b)
Classification. Class II (performance standards).