· ProBx Software is a computer-based image-guidance accessory intended for use in conjunction with commercially available Magnetic Resonance Imaging (MRI) systems and interventional devices.

· ProBx Software helps physicians guide biopsy instrumentation to targets that have been defined by the physician in MRI. The Software provides the clinician with image analysis and display of pre-procedural MRI images of tracked accessory hardware and the target organs, along with the projected path to the Software displays an MRI image of the current location of the interventional instrument for positioning confirmation.

· ProBx Software is intended to be used by physicians in a clinical setting for treatment planning and guidance for clinical, interventional, and/or diagnostic procedures of the prostate.

Device Description

ProBx Software along with ProBx Hardware accessories is used for in-bore Magnetic Resonance Imaging (MRI) guided interventional and diagnostic procedures of the prostate. The ProBx Software is intended to be loaded onto a commercially available workstation and used as an accessory to commercially available MRI systems. The software receives pre-procedural and intra-procedural DICOM images and provides 2D and 3D visualization for treatment planning. The Software performs calculations on user-selected target locations to assist the clinician in manually utilizing the tracked accessory hardware to reach targets. The Software also provides MRI scan confirmation of positioning during the procedure.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the ProBx Software, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria / Performance Metric	Reported Device Performance	Notes
Needle Placement Accuracy (End-to-End)	1.88 mm	This was demonstrated in a simulated clinical use phantom study. It was compared against the published accuracy of the predicate device (DynaCAD).
Non-inferiority to predicate device (DynaCAD) in needle placement accuracy	Demonstrated non-inferiority	The reported 1.88 mm accuracy for ProBx Software was considered non-inferior to the published end-to-end needle placement accuracy of DynaCAD. Specific numerical value for DynaCAD's published accuracy is not provided in this document, but the statement implies ProBx met or exceeded a benchmark set by the predicate.
Fiducial Registration Technique Validation	Validated	Bench testing was performed using "acceptable scientific methods" for this validation. No specific quantitative metric or target is provided beyond "validated."
Software Verification and Validation Testing	Successful (functions as intended)	This general criterion is stated to have supported the proposed indications for use and that the software functions as intended when used with ProBx Hardware accessories for prostate interventional procedures. No specific quantitative metrics for V&V tests are detailed in this summary, beyond the needle placement accuracy.
Compliance with referenced standards:- ISO 15223-1:2016- ISO 14971:2007- IEC 62304:2006	Device designed and developed in accordance with these standards	The device was developed referencing these standards, indicating compliance with general medical device and software development best practices.

2. Sample Size Used for the Test Set and Data Provenance

The document mentions "Bench testing" and a "simulated clinical use phantom study."

Test Set Description: Phantom study.
Sample Size: Not explicitly stated. The number of phantom procedures or measurements taken during the "simulated clinical use phantom study" is not provided.
Data Provenance: This was an internal "preclinical software verification and validation testing" using a phantom. It is therefore retrospective in the sense that it's based on controlled lab testing, not real patient data. The country of origin for the data is not specified but is implied to be within the company's testing facilities (Harmonus, Inc., likely in Massachusetts, USA).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Number of Experts: Not specified.
Qualifications of Experts: Not specified.

It is common for phantom studies to use pre-defined, known values (ground truth) established by engineering or physics principles, rather than human expert consensus for a test set. In this case, the ground truth for needle placement accuracy would likely be the precisely known target location within the phantom as defined during its design. The process of setting up and performing the phantom study would be conducted by trained technical personnel, but these are not "experts" in the clinical sense of establishing a medical ground truth.

4. Adjudication Method for the Test Set

Not applicable. As a phantom study, ground truth is based on known physical parameters, not human interpretation requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. The study described is a preclinical phantom study focused on technical accuracy. The comparison to the predicate device (DynaCAD) is based on "published end-to-end needle placement accuracy" of DynaCAD, not a direct comparative clinical study involving human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the described "simulated clinical use phantom study" that validated end-to-end needle placement accuracy of 1.88 mm is a form of standalone performance evaluation. While a human operator would manipulate the interventional hardware, the performance metric (accuracy) is a direct measure of the system's ability (software + hardware) to guide to a target, effectively evaluating the algorithm's guidance without comparing it to unassisted human performance or analyzing human interpretation.

7. The Type of Ground Truth Used

The ground truth used for the phantom study assessing needle placement accuracy would be the known physical coordinates of the target within the phantom. This is an objective, precisely defined ground truth.

8. The Sample Size for the Training Set

The document does not mention a training set or any deep learning/machine learning components that would typically require one. The ProBx Software is described as an "image-guidance accessory" that "performs calculations on user-selected target locations." This suggests a rule-based or calculational software rather than one heavily relying on machine learning that would necessitate a large training dataset.

9. How the Ground Truth for the Training Set Was Established

As no training set is mentioned or implied, this question is not applicable.

Summary

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

Harmonus Inc. Nandini Murthy Regulatory Consultant 110 Canal St 3rd Floor Lowell, Massachusetts 01852

March 2, 2018

Re: K173312

Trade/Device Name: ProBx Software Regulation Number: 21 CFR 892.2050 Regulation Name: Picture Archiving and Communications System Regulatory Class: Class II Product Code: LLZ Dated: January 16, 2018 Received: January 18, 2018

Dear Nandini Murthy:

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. 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820);

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Page 2 - Nandini Murthy

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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Michael D. O'Hara
For

Robert A. Ochs, Ph.D Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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SECTION 4

INDICATIONS FOR USE STATEMENT

A completed Indications for Use Statement follows this page.

CONFIDENTIAL

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Indications for Use

510(k) Number (if known) K173312

Device Name

ProBx Software

Indications for Use (Describe)

ProBx Software is intended for use as follows:

· ProBx Software is a computer-based image-guidance accessory intended for use in conjunction with commercially available Magnetic Resonance Imaging (MRI) systems and interventional devices.

· ProBx Software is intended to be used by physicians in a clinical setting for treatment planning and guidance for clinical, interventional, and/or diagnostic procedures of the prostate.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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Traditional 510(k) Premarket Notification Submission

SECTION 5

510(k) SUMMARY

Submitter Name:	Harmonus, Inc.
Submitter Address:	110 Canal St. Lowell, MA 01852
Contact Person:	Nicole Mauro, CEO
Phone Number:	(617) 702-2271
Date Prepared:	10/18/2017
Device Trade Name:	ProBx Software
Device Common Name:	Image-guided, interventional planning software
Classification Name:	System, Image Processing, Radiological, LLZ
Classification regulation:	21 CFR 892.2050, Product Code LLZ
Predicate Device:	DynaCAD/Prostate Interventional, K133030

Device Description:

Indications for Use:

ProBx Software is intended for use as follows:

ProBx Software is a computer-based image-guidance accessory intended for use in conjunction with commercially available Magnetic Resonance Imaging (MRI) systems and interventional devices.
ProBx Software helps physicians guide biopsy instrumentation to targets that have been defined by the physician in MRI. The Software provides the clinician with image analysis and display of pre-procedural and intra-procedural MRI images of tracked accessory hardware and the target organs, along with the projected path to the target. The Software displays an MRI image of the current location of the interventional instrument for positioning confirmation.

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Traditional 510(k) Premarket Notification Submission

ProBx Software is intended to be used by physicians in a clinical setting for treatment planning and guidance for clinical, interventional, and/or diagnostic procedures of the prostate.

	Submitted Device	Predicate Device #1	Reference Device #1
Proprietary/Trade Name	ProBx Software	DynaCAD/ProstateInterventional	SmartTarget
510(k) Number	n/a	K133030	K170250
Product Code	LLZ	LLZ	LLZ
Class	II	II	II
Target Anatomy	Prostate	Prostate	Prostate
Anatomy access	Transperineal	Transrectal	Transperineal
Modality	MR	MR	US fusion with MR, CT
Software
Windows OS	Yes	Yes	Yes
Kiosk	Yes	Yes	Not known
Medical Imaging Software	Yes	Yes	Yes
Connectivity
DICOM Import	Yes	Yes	Yes
Image Display
General Image 2D/3DReview	Yes	Yes	Yes
Image Processing
Registration: Fiducial-tracked Instrumentationin relation to patientanatomy	Yes	Yes	Yes
Required instrumentregistration andverification images priorto intervention	Yes	Yes	Yes
Planning and Navigation
InterventionalHardware/PositioningDevice	Yes (ProBx Grid withCalibrator and PatientSupport)	Yes (DynaTrim NeedleGuide and PatientSupport)	Yes (3rd partyGridplate and Stepper)
Add Targets	Yes	Yes	Yes
Plan/Marks Location	Yes	Yes	Yes
MR-guided interventionalplanning withinterventional hardware	Yes	Yes	Fusion with US

Rationale for Substantial Equivalence:

Table 5.1 Comparison of ProBx to Predicate Devices

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Traditional 510(k) Premarket Notification Submission

The ProBx software application is substantially equivalent to the predicate device (DynaCAD, K133030) in the areas of technological characteristics such as basic design, function, method of operation, application, and intended use.

Both software:

operate in Windows and function as a kiosk.
are able to import DICOM image from various sources and provide 2D and 3D image display.
are used with a positioning device and interventional hardware.
register fiducial-tracked instrumentation in relation to the patient anatomy.
provide verification images of instrumentation placement.
do not steer or in any way control the positioning of instruments used. ●
allow the procedure to be repeated based on operator judgement.
are intended for use in MR-guided procedures involving the prostate.

ProBx differs slightly from the DynaCAD in the anatomy access point, fiducial placement and type of needle guide hardware. The transperineal approach using a grid in ProBx is used in reference devices (SmartTarget, K170250). The placement of fiducials is accounted for in an equivalent technique of instrumentation registration. Therefore, the new device does not raise any new potential questions related to safety or performance, and is equivalent to the existing legally marketed devices.

Performance Data:

The ProBx software proposed indications for use are supported by preclinical software verification and validation testing. Bench testing was performed using acceptable scientific methods to validate the fiducial registration technique and determine substantial equivalence to the predicate. This includes validation of the software with the ProBx Hardware in a simulated clinical use phantom study that showed our device can achieve end-to end needle placement accuracy of 1.88 mm. This result shows the ProBx Software is non-inferior to the published endto end needle placement accuracy of DynaCAD.

The following are the referenced standards during design and development of the ProBx Software:

ISO 15223-1:2016, Medical devices Symbols to be used with medical device labels, labeling and information to be supplied
ISO 14971:2007, Medical Devices Application of Risk Management to Medical Devices
IEC 62304:2006, Medical Device Software Software Life Cycle Processes

Conclusion:

ProBx Software has similar indications statements as the predicate device. Both devices are used for MR-guided interventional planning with interventional hardware for procedures involving the prostate. The functionality of the ProBx Software and the predicate device is

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Traditional 510(k) Premarket Notification Submission

identical. The results of software verification and validation testing support that ProBx Software functions as intended when used with ProBx Hardware accessories for prostate interventional procedures. Therefore, ProBx Software is substantially equivalent to the predicate device.

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).