The Stone Clear ultrasonic propulsion device is indicated for the repositioning of residual stone fragments post-lithotripsy that are located in the upper urinary tract of adult patients to facilitate passage, where any individual fragment is less than or equal to 5 mm.

Device Description

The Stone Clear device consists of a commercially available third-party diagnostic ultrasound imaging unit (GE LOGIQ P9, K181783, Imaging Workstation) that is integrated with a SonoMotion-manufactured signal generator and therapy probe.

The Imaging Workstation and associated ultrasound imaging provide the user interface and real-time image guidance for the Stone Clear procedure, while the Generator controls and drives the Therapy Probe. The Therapy Probe delivers the ultrasound pulses to reposition stones. The Imaging Probe and Therapy Probe are coaxially aligned, with the Imaging Probe docking into the housing of the Therapy Probe through an adapter. A foot pedal is used to initiate the therapy from the Generator.

AI/ML Overview

The provided text describes the regulatory information, device description, nonclinical/bench studies, and clinical information (including results and benefit-risk determination) for the Stone Clear ultrasonic urinary stone propulsion device.

However, the provided text does not contain any information about acceptance criteria or a study design to prove that an AI/ML algorithm meets acceptance criteria. The "Stone Clear" device is a physical medical device, not an AI/ML algorithm. The "Software" section primarily describes the device's control firmware and user interface, without any indication of AI/ML components for classification, prediction, or diagnostic assistance.

Therefore, I cannot fulfill the request as it asks for information that is not present in the provided input text. The prompt's questions pertain to acceptance criteria and studies for AI/ML performance (e.g., sample size for test/training sets, data provenance, expert labeling, MRMC studies, standalone performance, ground truth establishment), which are irrelevant to the description of the Stone Clear device.

Summary

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

DE NOVO CLASSIFICATION REQUEST FOR STONE CLEAR

REGULATORY INFORMATION

FDA identifies this generic type of device as:

Ultrasonic urinary stone propulsion device. An ultrasonic urinary stone propulsion device visualizes urinary stones in the upper urinary tract and delivers focused acoustic pulses to reposition the stones to facilitate their passage.

NEW REGULATION NUMBER: 21 CFR 876.4690

CLASSIFICATION: Class II

PRODUCT CODE: Q QNA

BACKGROUND

DEVICE NAME: Stone Clear

SUBMISSION NUMBER: DEN230082

DATE DE NOVO RECEIVED: December 7, 2023

SPONSOR INFORMATION:

SonoMotion, Inc. 1600 W. Hillsdale Blvd. Suite 105 San Mateo, CA 94402

INDICATIONS FOR USE

LIMITATIONS

The sale, distribution, and use of the Stone Clear are restricted to prescription use in accordance with 21 CFR 801.109.

PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS.

{1}------------------------------------------------

DEVICE DESCRIPTION

Image /page/1/Picture/3 description: The image shows a GE ultrasound machine. The machine has a large monitor at the top and a smaller monitor on the control panel. The control panel has several buttons and knobs. The machine is on wheels and has a blue base.

Ultrasound Imaging System and Imaging Probe

The Ultrasound Imaging System has been modified for SonoMotion with a proprietary user interface, synchronization signal (for synchronizing imaging and therapy), and integration between the imaging system and Generator.

The 3Sc-RS phased array Imaging Probe is integrated with the Therapy Probe for real-time monitoring of stone motion and cavitation during treatment.

Therapy Probe

The Therapy Probe delivers the focused ultrasound pulses that result in stone motion.

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

Image /page/2/Picture/0 description: The image contains three different views of ultrasound probes. The first image, labeled (a) Top view, shows the top of the probe and its base. The second image, labeled (b) Side View, shows the side of the probe and its base. The third image, labeled (c) Probes shown individually, shows the probes detached from the base.

Generator

The Generator is an external unit that provides the electrical excitation to the Therapy Probe that causes the stone to move. The Generator has no user controls and is enclosed within the printer bay of the LOGIO P9 imaging system. The Generator also contains the system firmware which interfaces with the Imaging Workstation. The Generator determines when therapy pulses are allowed and what therapy related messages and warnings will be displayed on the Imaging Workstation screen.

Software

The system includes two primary software environments - Imaging Workstation (off the shelf ultrasound imaging system) and Generator (two microcontrollers and an FPGA residing on the Generator Main Board). The Imaging Workstation software is responsible for displaying the information to the user interface and passing parameter value changes from the user interface control elements to the Generator. The Imaging Workstation is also responsible for enabling/disabling the synchronization signal and serial communication with the Generator.

As stated above, the Generator software interfaces with the Imaging Workstation and drives the Therapy Probe.

SUMMARY OF NONCLINICAL/BENCH STUDIES

The following non-clinical test were leveraged to demonstrate safety and effectiveness for the subject device's indication for use.

REPROCESSING, STERILITY AND SHELF-LIFE

The Stone Clear is provided non-sterile and requires reprocessing prior to its first and subsequent uses for cleaning and disinfection. Reprocessing methods in the labeling were validated per the FDA Reprocessing guidance entitled, "Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling" and AAMI TIR30:2011(R) 2016.

BIOCOMPATIBILITY

The Stone Clear, per Table A.1 of the FDA Biocompatibility guidance entitled, "Use of International Standard ISO 10993-1, "Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process" is a surface device with direct contact with skin for a limited duration (< 24 hours).

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

The following testing was conducted to demonstrate biocompatibility per the above patient contact types and considered adequate:

ISO 10993-5 third edition 2009, "Biological evaluation of medical devices Part ● 5: Tests for in vitro cytotoxicity"
ISO 10993-10, fourth edition 2021, "Biological evaluation of medical devices -● Part 10: Tests for skin sensitization"
ISO 10993-23, first edition 2021, "Biological evaluation of medical devices Part ● 23: Tests for irritation"

Biocompatibility testing was conducted consistent with ISO 10993-1 fifth edition 2018, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" and the FDA Guidance Document, Use of International Standard ISO 10993-1: 2016, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" Guidance for Industry and Food and Drug Administration Staff.

SOFTWARE & CYBERSECURITY

A failure or latent flaw in the software of the Stone Clear would not directly result in severe injury or death to the patient: therefore, the software of this device is considered to require "Basic Documentation". Adequate software documentation and software testing were provided as per the FDA Software guidance entitled, "Content of Premarket Submissions for Device Software Functions".

The device is not a cyber device as determined by section 524B of the FD&C act. Therefore, cybersecurity is not applicable.

ELECTROMAGNETIC COMPATIBILITY & ELECTRICAL SAFETY

Electromagnetic compatibility was evaluated in accordance with ANSI/AAMI/IEC60601-1-2:2014/A1:2021 "Medical Electrical Equipment - Part 1-2: General Requirements for Basic Safety and Essential Performance-Collateral Standard: Electromagnetic disturbances - Requirements and Tests."

Electrical safety was evaluated in accordance with ANSI/AAMI/ES60601-1:2005/(R)2012 & A1:2012 C1:2009/(R)2012 & A2:2010/(R)2012, "Medical Electrical Equipment; Part I: General requirements for basic safety and essential performance."

NON-CLINICAL PERFORMANCE TESTING - BENCH

The following performance tests were conducted to support that the device can achieve its intended use:

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

Acoustic Power and Intensity (AP&I) per NEMA UD2 Rev 3 "Acoustic Output . Measurement Standard for Diagnostic Ultrasound Equipment, Revision 3", IEC 60601-2-37, "Medical electrical equipment - Part 2-37: Particular requirements for basic safety and essential performance of ultrasonic medical diagnostic and monitoring equipment", IEC 60601-2-5, "Medical electrical equipment - Part 2-5: Particular requirements for the safety of ultrasonic physiotherapy equipment'', IEC 60601-2-36, "Medical electrical equipment - Part 2-36: Particular requirements for basic safety and essential performance of equipment for extracorporeally induced lithotripsy" and "IEC 61846, Ultrasonics - Pressure pulse lithotripters - Characteristics of fields."
Focal Geometry and Targeting Accuracy per IEC 60601-2-36 "Medical electrical equipment - Part 2-36: Particular requirements for basic safety and essential performance of equipment for extracorporeally induced lithotripsv" and "IEC 61846. Ultrasonics - Pressure pulse lithotripters - Characteristics of fields."
. Probe Surface Heating per IEC 60601-2-37, "Medical electrical equipment - Part 2-37: Particular requirements for basic safety and essential performance of ultrasonic medical diagnostic and monitoring equipment."
. Therapy Probe verification testing and reliability testing to ensure the probe meets the specifications for its intended purpose and maintains performance integrity over its intended use life using simulated use cycles The verification testing included probe locking force, probe mating alignment, probe registration, and cable bending and twisting load.
Mechanical strength testing per IEC 60601 -1 :2005, AMD1:2012 "Medical Electrical Equipment; Part I: General requirements for basic safety and essential performance."

ANIMAL TESTING

The safety of extreme treatment exposure for acute and long-term effects was conducted on 9 pigs (18 kidneys) in a 7-day survival study. The study was performed to assess the potential for renal tissue injury from worst-case parameters of the device. The pigs were treated with a burst with a maximum un-derated spatial peak pulse average intensity of 200 W/cm² delivered continuously for 10 minutes on a single site per kidney. No stones were present. Histological pathology evaluation of tissues from this study revealed no device related evidence of injury at the focus or within the pre- or post- focal region at maximum treatment conditions.

SUMMARY OF CLINICAL INFORMATION

The clinical testing included a prospective, multi-center, two-arm randomized controlled trial. The study was conducted to assess the ability of the Stone Clear to reposition stones within the kidney and the subsequent clinical benefit of facilitating stone passage and reducing stone

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

burden. Subjects were selected from patients who had undergone a lithotripsy procedure to fragment urinary stones at least four weeks prior to randomization and still had residual stone fragments post-lithotripsy. The procedure targeted fragments 5mm or less in size, or clusters of fragments. Control arm subjects did not undergo the device procedure but maintained standard of care for the residual stone fragments. Data was presented on two cohorts, the ITT population (24 treatment arm, 22 control arm) and the Supplemental population (12 treatment arm, 12 control arm). The ITT study was conducted at 2 sites, and the Supplemental study was conducted at 2 additional sites with six new users. The primary effectiveness endpoint was measured by subjects reporting visual observation of stone passage in the 3 weeks following randomization.

Inclusion Criteria

Subjects of the study were required to meet the following criteria for entrance to the study:

Individuals suspected of having at least one stone remaining from the lithotripsy procedure
· Individuals at least 4-weeks post-lithotripsy procedure
Individuals with residual stone fragments < 5 mm in largest dimension (individually)
· Individuals being managed with watchful waiting or medical therapy for stones

Exclusion Criteria

Subjects were excluded from the study if they met any of the following criteria:

Individuals under 18 years of age
· Individuals with stones that are not visible with ultrasound
· Individuals not available for follow-up or unwilling to do follow-up
· Individuals with a coagulation abnormality or taking blood thinners or other anticoagulants at clinically significant levels
· Individuals with mobility issues who are unable to comfortably lie for up to 30 minutes or roll from their back to their side
· Individuals belonging to a vulnerable group (pregnant, mentally disabled, prisoner, etc.)
· Individuals who have already received four previous ultrasonic propulsion treatments
· Individuals who have received an ultrasonic propulsion treatment within the last month (4 weeks)

Study Endpoints:

Primary Effectiveness Endpoint:

The primary effectiveness endpoint was the proportion of subjects reporting visual observation of stone passage over 3-weeks following treatment (Treatment group) or randomization (Control group). The superiority of the Treatment group compared to the Control group was assessed.

Primary Safety Endpoint:

The primary safety endpoint was the subject-level rate of low frequency adverse events (AEs) of interest defined as skin burn, clinically significant hematuria, renal injury requiring intervention, clinically significant hematoma, sepsis, or any other procedure or device related event meeting the definition of a serious adverse event (SAE) with onset after the initial procedure (Treatment group) or randomization (Control group) through the 3-week follow-up.

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

Secondary Endpoints:

The secondary effectiveness endpoint was demonstrating superiority with a 7.5% margin for the proportion of subjects reporting visual observation of stone passage during the 3-week follow-up period following treatment (Treatment group) or randomization (Control group).

The secondary safety endpoint was the subject-level rate of all adverse events with onset after the procedure through 3-weeks after treatment (Treatment group) or randomization (Control group).

Results:

Stone passage rate in the ITT cohort was 83.3% (20/24) in the Treatment group compared to 4.5% (1/22) in the Control group, corresponding to a 78.8% difference (95% CI - 53.1% to 92.7%: p-value <0.05). For the 20 subjects who reported passage of stone fragments. 2 subjects (10%) were identified as stone free on follow-up imaging. The remaining 18 subjects did not completely pass the target fragment cluster(s) after one procedure.

In the supplemental population, the stone passage rate was 83.3% (10/12) in the Treatment group compared to 16.7% (2/12) in the Control group, corresponding to a 66.6% difference (95% CI: -25.2% to 90.5%).

Subgroup	Category	ITT TreatmentGroup	ITTControlGroup	SupplementalTreatment Group	SupplementalControl Group
Overall		20/24 (83.3%)	1/22 (4.5%)	10/12 (83.3%)	2/12 (16.7%)
Sex	Male	13/16 (81.3%)	1/11 (9.1%)	5/6 (83.3%)	1/6 (16.7%)
	Female	7/8 (87.5%)	0/11 (0%)	5/6 (83.3%)	1/6 (16.7%)
Ethnicity	Non-Hispanic	19/23 (82.6%)	1/18 (5.6%)	9/11 (81.8%)	2/12 (16.7%)
	Hispanic	1/1 (100%)	0/4 (0.0%)	1/1 (100%)	0/0 (n/a)
Race	White orCNR*	18/22 (81.8%)	1/18 (5.6%)	7/9 (77.8%)	2/10 (20.0%)
		2/2 (100%)	0/4 (0%)	2/3 (66.7%)	0/2 (0%)
	Non White
KidneySide	Right	3/4 (75.0%)	1/8 (0.1%)	2/3 (66.7%)	0/5 (0%)
	Left	17/20 (85.0%)	0/14 (0%)	8/9 (88.9%)	2/7 (28.6%)

The following table describes the rates of subjects reporting stone passage overall and broken down by demographics:

*chose not to report

No SAEs, unanticipated adverse device effects (UADEs), or low frequency AEs of interest were reported. AEs were primarily mild and transient, and resolved without sequalae or intervention. The Treatment group showed an increase in the rate of mild AEs, consistent with events typical of symptomatic stone passage including urinary urgency, urinary frequency, nausea, and hematuria. The safety results were the same between the ITT and supplemental study populations.

Subject Demographics:

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

	ITT TreatmentGroup	ITTControl Group	SupplementalTreatmentGroup	SupplementalControl Group
Sex
Male	16 (66.7%)	11 (50.0%)	6 (50.0%)	6 (50.0%)
Female	8 (33.3%)	11 (50.0%)	6 (50.0%)	6 (50.0%)
Age
Mean ± SD	54 ± 17	59 ± 15	72 ± 8	59 ± 11
Median (25%-75% Q)	57 (40-70)	62 (48-72)	70 (70-75)	64 (55-67)
Range	23 – 78	31 - 77	59 - 92	34 - 72
BMI
Mean ± SD	28 ± 4	29 ± 8	28 ± 7	29 ± 8
Median (25%-75% Q)	27 (24-30)	27 (25-34)	28 (24-30)	28 (24-31)
Range	19 - 37	18 - 48	17 - 44	20 - 45
Race
White	22 (91.6%)	18 (81.8%)	9 (75.0%)	10 (83.3%)
African American	1 (4.2%)	2 (9.1%)	1 (8.3%)	0 (0.0%)
Asian	0 (0.0%)	0 (0.0%)	0 (0.0%)	2 (16.7%)
Multiracial	0 (0.0%)	0 (0.0%)	1 (8.3%)	0 (0.0%)
Chose not to report	1 (4.2%)	2 (9.1%)	1 (8.3%)	0 (0.0%)
Ethnicity
Non-Hispanic	23 (95.8%)	18 (81.8%)	11 (91.7%)	12 (100%)
Hispanic	1 (4.2%)	4 (18.2%)	1 (8.3%)	0 (0.0%)
Kidney Side
Right	4 (16.7%)	8 (36.4%)	3 (25.0%)	5 (41.7%)
Left	20 (83.3%)	14 (63.6%)	9 (75.0%)	7 (58.3%)

Device Related Adverse Events:

The following table lists all adverse events reported for the safety results include the ITT and supplemental study cohorts, as well as a historical cohort of subjects that underwent the device procedure in a separate clinical study (the historical results are not included for the effectiveness assessment):

	Treatment Group(N = 54)		Control Group(N = 54)
	Subjects	percent	Subjects	percent
Skin Effects	3	(5.6%)	0	(0.0%)
Pain	21	(38.9%)	17	(31.5%)
Hematuria	4	(7.4%)	3	(5.6%)
Urinary Frequency	6	(11.1%)	3	(5.6%)
Urinary urgency	5	(9.3%)	0	(0.0%)
Slow flow;incompleteemptying	2	(3.7%)	1	(1.9%)
Dysuria	4	(7.4%)	2	(3.7%)
Nausea	3	(5.6%)	3	(5.6%)
Vomiting	0	(0.0%)	2	(3.7%)
Constipation	3	(5.6%)	0	(0.0%)
Diarrhea	5	(9.3%)	2	(3.7%)
Other*	4	(7.4%)	2	(3.7%)

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

Subjects with atleast 1 AE	31(57.4%)	21(38.9%)
--------------------------------	---------------	---------------

*1 subject reported each of Covid, fatigue/thirsty/itchy, headache, and malodorous urine in the Treatment group and distended/uncomfortable and headache in the Control group.

Pediatric Extrapolation:

In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population.

LABELING

The device user manual includes a description of the device technical parameters and instructions for use for the device. The user manual contains relevant findings from the clinical study. The user manual also states the necessary measures to properly clean the reusable components of the device.

Labeling for this device is in accordance with the special controls listed below.

RISKS TO HEALTH

The table below identifies the probable risks to health that are associated with use of an ultrasonic urinary stone propulsion device:

Risks to Health	Mitigation Measures
Pain or discomfort	Clinical performance dataLabeling
Damage to underlying tissue fromexcessive or mistargeted ultrasoundapplication due to mechanical failure,software malfunction, or use error	Non-clinical performance testingSoftware verification and validationLabeling
Thermal injury	Non-clinical performance testing
Unsuccessful repositioning	Clinical performance dataLabeling
Urinary obstruction	Clinical performance dataLabeling
Hematuria	Clinical performance dataLabeling
Adverse tissue reaction	Biocompatibility evaluation
Infection	Reprocessing validation
Electrical shock, burn, or interference	Electrical safety testingElectromagnetic compatibility (EMC) testing

SPECIAL CONTROLS

{9}------------------------------------------------

In combination with the general controls of the FD&C Act, the ultrasonic urinary stone propulsion device is subject to the following special controls:

(1) Clinical performance data must demonstrate that the device performs as intended under anticipated conditions of use. Data must evaluate the following:
- The device performance in repositioning urinary stones and facilitating their (i) passage: and
- (ii) Device and procedure related adverse events, including pain, discomfort, hematuria, and urinary obstruction.
(2) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
- Acoustic output characteristics, including acoustic power and intensity, focal (i) geometry, and target accuracy; and
- Probe surface heating. (ii)
(3) Performance testing must demonstrate the electromagnetic compatibility (EMC), electrical safety, and mechanical safety of the device in the intended use environment.
(4) Performance data must demonstrate that all patient-contacting components of the device are biocompatible.
(5) Performance data must validate the reprocessing instructions for the reusable components of the device.
(6) Software verification, validation, and hazard analysis must be performed.
(7) Labeling must include:
- The size of the stones treated with the device; (i)
- The acoustic properties of the device: (ii)
- (iii) Specific instructions on identifying an appropriate acoustic window;
- (iv) Summary of the clinical performance data conducted with the device; and
- (v) Reprocessing instructions.

BENEFIT-RISK DETERMINATION

Risks

The probable risks of the device are based on nonclinical laboratory studies as well as data collected in the clinical testing described above.

These risks include:

Injury to urinary or kidney tissue due to misplaced or excessive ultrasonic pressure ●
Pain or discomfort from stone repositioning ●
Temporary skin effects at probe application site

The risks for this device are also those typical of stone passage and post-lithotripsy effects, such as nausea, transient hematuria, urinary urgency and frequency, dysuria, constipation, and diarrhea.

{10}------------------------------------------------

The device also includes risks for adverse biological reaction and infection at the probe application site, thermal injury from probe overheating, and electrical shock from the electrical components. These risks have all been mitigated through completion of performance testing, warnings, precautions, and special controls.

Benefits

The benefits of the device are based on the clinical testing described above. The results demonstrate the probable benefit of the device in facilitating stone passage of residual stone fragments less than 5mm within three weeks compared to watchful waiting or medical therapy.

Patient Perspectives

The clinical study assessed changes in pre- to post-procedure pain based on pain scores reported by subjects in the treatment group. Only 2 of the 24 treatment subjects reported an increase in pain post-procedure. These pain scores were also compared to those reported by the subjects in the control group. A comparison between the groups showed no significant difference between the post-procedure treatment subjects and control subjects without the procedure.

Benefit/Risk Conclusion

In conclusion, given the available information above, for the following indication statement:

The probable benefits outweigh the risks for the Stone Clear. The device provides benefits, and the risks can be mitigated by the use of general controls and the identified special controls.

CONCLUSION

The De Novo request for the Stone Clear is granted and the device is classified as follows:

Product Code: ONA Device Type: Ultrasonic urinary stone propulsion device Regulation Number: 21 CFR 876.4690 Class: II

Regulation Number and Section

N/A