TULSA-PRO System

K191200 · Profound Medical, Inc. · PLP · Aug 15, 2019 · Gastroenterology, Urology

Device Facts

• Record ID: K191200
• Device Name: TULSA-PRO System
• Applicant: Profound Medical, Inc.
• Product Code: PLP · Gastroenterology, Urology
• Decision Date: Aug 15, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 876.4340
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The TULSA-PRO System is indicated for transurethral ultrasound ablation (TULSA) of prostate tissue.

Device Story

TULSA-PRO system performs thermal ablation of prostate tissue using transurethral directional ultrasound under real-time MRI guidance. System includes transurethral ultrasound applicator (UA) and transrectal endorectal cooling device (ECD) to protect rectal wall. Physician uses console to plan treatment by contouring tissue on high-resolution MR images. Closed-loop software processes real-time MR thermometry data to dynamically adjust ultrasound frequency, power, and rotation rate. UA rotates 360 degrees to deliver continuous thermal coagulation to prescribed volume. Used in MRI suite; operated by physician. Output provides precise thermal ablation of prostate tissue while sparing urethra and urinary sphincter. Benefits include customized treatment planning and real-time monitoring to minimize thermal damage to critical surrounding structures.

Clinical Evidence

Prospective TACT pivotal study (n=115) evaluated safety and effectiveness in patients with organ-confined prostate cancer. Primary efficacy endpoint: PSA reduction ≥75% achieved in 96% of patients. Median prostate volume reduction was 91.4% at 12 months. Safety endpoints included CTCAE-graded adverse events; no rectal injury, fistula, or severe urinary incontinence/dysfunction reported. 7.8% of patients experienced attributable Grade 3 adverse events, all resolved by 12 months. 63% of patients showed complete histological response on 12-month biopsy (ITT analysis).

Technological Characteristics

System comprises console, PC, TULSA-PRO software, water cooling circuit, transurethral UA, and transrectal ECD. UA uses linear array of 10 planar rectangular ultrasound elements (4-4.8 MHz low frequency; 13.4-14.4 MHz high frequency). Closed-loop controller manages frequency, power, and rotation. Complies with IEC 60601-1, IEC 60601-2-62, ISO 10993, and ISO 14971. Sterilization via ethylene oxide. Connectivity includes MRI interface for real-time thermometry.

Indications for Use

Indicated for transurethral ultrasound ablation (TULSA) of prostate tissue in patients with organ-confined prostate cancer.

Regulatory Classification

Identification

A high intensity ultrasound system for prostate tissue ablation is a prescription device that transmits high intensity therapeutic ultrasound energy into the prostate to thermally ablate a defined, targeted volume of tissue, performed under imaging guidance. This classification does not include devices that are intended for the treatment of any specific prostate disease and does not include devices that are intended to ablate non-prostatic tissues/organs.

Special Controls

In combination with the general controls of the FD&C Act, the high intensity ultrasound system for prostate tissue ablation is subject to the following special controls:

*Classification.* Class II (special controls). The special controls for this device are:(1) Non-clinical performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested: (i) Characterization of acoustic pressure and power output at clinically relevant levels; (ii) Measurement of targeting accuracy and reproducibility of high intensity ultrasound output; (iii) Ultrasound-induced heating verification testing at target and non-target tissues; (iv) Electrical safety testing; and (v) Electromagnetic compatibility testing. (2) Software verification, validation, and hazard analysis must be performed. (3) The elements of the device that may contact the patient's mucosal tissue must be demonstrated to be biocompatible. (4) Performance data must demonstrate the sterility of the device components that contact the patient's mucosal tissue. (5) Performance data must support shelf life by demonstrating continued sterility of the device or the sterile components, package integrity, and device functionality over the identified shelf life. (6) Performance data must support the instructions for reprocessing all reusable components. (7) *In vivo* testing must demonstrate that the device thermally ablates targeted tissue in a controlled manner without thermal injury to adjacent, non-target tissues.(8) Clinical testing must document the adverse event profile, provide evidence of prostatic ablation, and demonstrate that the device performs as intended under anticipated conditions of use. (9) Training must be provided so that upon completion of the training program, the physician can: (i) Use all safety features of the device; (ii) Accurately target the high intensity ultrasound energy within the desired region of the prostate; and (iii) Perform the ablation procedure in a manner that minimizes damage to non-target tissues. (10) Labeling must include: (i) A section that summarizes the clinical testing results, including the adverse event profile and evidence of prostate ablation achieved; and (ii) An expiration date or shelf life for single use components.

Predicate Devices

• Ablatherm Integrated Imaging (K153023)

Submission Summary (Full Text)

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August 15, 2019

Profound Medical Inc. Goldy Singh VP, Clinical and Regulatory Affairs 2400 Skymark Avenue, Unit #6 Mississauga Ontario L4W5K5 CANADA

Re: K191200

Trade/Device Name: TULSA-PRO System Regulation Number: 21 CFR 876.4340 Regulation Name: High Intensity Ultrasound System for Prostate Tissue Ablation Regulatory Class: Class II Product Code: PLP Dated: July 16, 2019 Received: July 17, 2019

Dear Goldy Singh:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

for Glenn B. Bell, Ph.D. Assistant Division Director DHT3B: Division of Reproductive, Gynecology and Urology Devices OHT3: Office of Gastrorenal, ObGyn, General Hospital and Urology 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) K191200

Device Name TULSA-PRO SYSTEM

Indications for Use (Describe)

The TULSA-PRO System is indicated for transurethral ultrasound ablation (TULSA) of prostate tissue.

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)

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## 510(k) Summary

#### l. General Information

- ' Applicant Name: Profound Medical Inc. 2400 Skymark Avenue, Unit #6, Mississauga, ON L4W 5K5, Canada T: 647.476.1350 F: 647.847.3739
- 트 Regulatory contact: Goldy Singh VP Clinical & Regulatory Affairs 2400 Skymark Avenue, Unit #6, Mississauga, ON L4W 5K5, Canada Phone: [phone] × 403 Fax: [phone] Email: [e-mail]
- ' Date Prepared: 2 Aug 2019

#### ll. Device Identification

- 트 Proprietary Name: TULSA-PRO System
- ' Common Name: High Intensity Ultrasound System for Prostate Tissue Ablation
- ' Regulatory Class: Class II
- Regulation Name: High Intensity Ultrasound System for Prostate Ablation
- I Regulation Number: 21 CFR 876.4340
- ' Product Code: PLP (High Intensity Ultrasound System for Prostate Ablation)

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Image /page/4/Picture/1 description: The image contains the logo for Profound Medical Inc. The logo is in blue and consists of the word "PROFOUND" on the top line and the word "MEDICAL" on the bottom line. The letters "OU" in "PROFOUND" are connected by a horizontal line with a dot in the middle. The word "Inc." is in a smaller font size and is located to the right of the word "MEDICAL".

#### III. Predicate Device Information

| Predicate Device | Ablatherm Integrated Imaging |
|------------------|------------------------------|
| 510(k) Number | K153023 |
| Decision Date | Nov 6, 2015 |
| Manufacturer | EDAP Technomed, Inc. |

#### IV. Device Description

The TULSA-PRO system combines real-time Magnetic Resonance (MR) imaging and MR thermometry with transurethral directional ultrasound and closed-loop process control software to deliver precise thermal ablation of a customized volume of physician prescribed prostate tissue. The system consists of both hardware and software components.

Transurethral ultrasound ablation (TULSA) treatment ablates prostate tissue using in-bore real-time MRI treatment planning, monitoring, visualization, and active temperature feedback control. The closed-loop features of the TULSA-PRO software use a real-time MRI interface to process MRI prostate temperature measurements, and communicate with the TULSA-PRO hardware, thereby controlling frequency, power and rotation rate of ultrasound to ablate physician prescribed prostate tissue with a high degree of precision.

The physician inserts two catheters, one transurethral and another transrectal, into the patient before he is moved into the MR bore. The transurethral catheter consists of an Ultrasound Applicator (UA) which delivers energy from the urethra outwards into the prostate tissue, heating it to thermal coagulation. The transrectal catheter is an Endorectal Cooling Device (ECD) which does not emit any energy, and cools the rectal wall adjacent to the prostate. Both catheters have fluid flowing inside throughout the treatment to thermally protect the urethra and rectum, in order to minimize the potential of any thermal damage to either the urinary or rectal pathways. The physician uses the TULSA-PRO console to robotically position the UA in the prostate and plan the treatment by contouring the prescribed tissue on realtime high-resolution cross-sectional MR images of the prostate. These features provide the physician with the ability and the control to customize the treatment plan to minimize thermal impact to critical structures surrounding the prostate including the external urethral sphincter, rectum and neurovascular bundles. The treatment begins based upon the physician's instructions by enabling the software to initiate thermal ablation. The TULSA-PRO closed-loop process control software reads real-time MR thermometry measurements and adjusts automatically and dynamically the frequency, power and rotation rate of ultrasound provided by each

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UA transducer, to deliver precise ablation of the prescribed prostate tissue. The software controls automated, continuous and robotic rotation of the transurethral UA by 360 degrees in sync with the process controlled delivery of thermal heating to all the intended regions of the prostate. Following completion of the ablation process, the two catheters are removed from the natural orifices of the patients.

#### V. Intended Use

The TULSA-PRO® System is indicated for transurethral ultrasound ablation (TULSA) of prostate tissue.

#### VI. Summary of Non-clinical testing

The following non-clinical testing was provided in support of this submission:

- . Bench Performance testing was conducted for the TULSA-PRO System to demonstrate that the system meets the requirements of the product design specification and performs in accordance with its intended use.
- Biocompatibility testing was conducted in accordance with ISO 10993-1:2018 Biological Evaluation of Medical Devices, Part 1: Evaluation and Testing within a Risk Management Process.
- . Software validation activities were performed in accordance with the FDA Guidance, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices."
- . Sterilization validation activities were performed in accordance with "ISO 11135 Second edition - Sterilization of health-care products - Ethylene oxide -Requirements for the development, validation and routine control of a sterilization process for medical devices."
- Electrical Safety and Electromagnetic Compatibility have been confirmed by a Nationally Recognized Testing Laboratory.
- Animal Studies – Animal studies were conducted on a canine prostate model.

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Image /page/6/Picture/1 description: The image shows the logo for Profound Medical Inc. The word "PROFOUND" is in large, blue, sans-serif font. There is a horizontal line going through the "O" in "PROFOUND". Below "PROFOUND" is the word "MEDICAL" in a smaller, blue, sans-serif font. To the right of "MEDICAL" is "Inc." in a smaller, blue, sans-serif font.

#### VII. Conformance to Recognized Standards

The TULSA-PRO System complies with applicable sections of the following recognized consensus standards:

- . IEC 60601-1:2005/A1:2012 – Medical electrical equipment – Part 1: General requirements for basic safety and essential performance
- IEC 60601-1-2 Edition 4.0 2014-02 Medical electrical equipment Part 1-2: . General requirements for basic safety and essential performance – Collateral Standard: Electromagnetic disturbances – Requirements and tests
- . IEC 60601-1-6 Edition 3.1 2013-10 – General requirements for basic safety and essential performance - Collateral standard: Usability
- ANSI/AAMI 62366-1 Edition 1.0 2015-02 Medical devices Part 1: Application ● of usability engineering to medical devices
- IEC 60601-1-8 Edition 2.1 2012-11 – Medical electrical equipment – Part 1-8: General requirements for basic safety and essential performance – Collateral Standard: General requirements, tests and guidance for alarm systems in medical electrical equipment and medical electrical systems
- . IEC 60601-1-10 Edition 1.1 2013-11 – Medical electrical equipment – Part 1-10: General requirements for basic safety and essential performance – Collateral Standard: Requirements for the development of physiologic closed-loop controllers
- . IEC 60601-2-62 Edition 1.0 2013-07- Medical Electrical Equipment - Part 2-62: Particular Requirements For The Basic Safety And Essential Performance Of High Intensity Therapeutic Ultrasound (HITU) Equipment
- . ISO 14971:2012 – Medical devices – Application of risk management to medical devices
- . ANSI/AAMI/IEC 62304 Edition 1.1 2015-06 – Medical device software – Software life cycle processes
- . ISO 10993-1 Fifth edition 2018-08 – Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process
- ISO 10993-4 Third edition 2017-04 – Biological evaluation of medical devices – Part 4: Selection of tests for interactions with blood
- ISO 10993-5 Third edition 2009-06-01 – Biological evaluation of medical devices – Part 5: Tests for in vitro cytotoxicity
- . ISO 10993-7 Second edition 2008-10-15 – Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals
- ISO 10993-10 Third Edition 2010-08-01 – Biological evaluation of medical devices – Part 10: Tests for irritation and skin sensitization

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Image /page/7/Picture/1 description: The image shows the logo for Profound Medical Inc. The logo is in blue and consists of the word "PROFOUND" in large, bold letters, with the word "MEDICAL" underneath in smaller letters. To the right of the word "MEDICAL" is the superscript "Inc.". There is a horizontal line going through the "O" in "PROFOUND" with a dot in the middle of the "O".

- ISO 10993-11 Third edition 2017-09 – Biological evaluation of medical devices – Part 11: Tests for systemic toxicity
- ISO 11135 Second edition 2014-07-15 – Sterilization of health-care products – Ethylene oxide – Requirements for the development, validation and routine control of a sterilization process for medical devices
- . ANSI/AAMI/ISO 11607-1:2006/(R) 2010 – Packaging for terminally sterilized medical devices - Part 1: Requirements for materials, sterile barrier systems and packaging
- . ANSI/AAMI/ISO 11607-2:2006/(R) 2010 - Packaging for terminally sterilized medical devices – Part 2: Validation requirements for forming, sealing and assembly processes
- . ISO 11737-1 Third edition 2018-01 – Sterilization of health care products – Microbiological methods – Part 1: Determination of a population of microorganisms on product
- . ANSI/AAMI/ISO 11737-2:2009/(R) 2014 - Sterilization of medical devices -Microbiological methods – Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process
- . EN ISO 14155 Second edition 2011-02-01 – Clinical investigation of medical devices for human subjects – Good clinical practice
- . ISO 15223-1 Third Edition 2016-11-01 – Medical devices – Symbols to be used with medical device labels, labelling, and information to be supplied
- . ASTM F2052-15 - Standard Test Method for Measurement of Magnetically Induced Displacement Force on Medical Devices in the Magnetic Resonance Environment
- . ASTM F2182-11a – Standard Test Method for Measurement of Radio Frequency Induced Heating on a Near Passive Implants during Magnetic Resonance Imaging
- . ASTM F2213-17 – Standard Test Method for Measurement of Magnetically Induced Torque on Medical Devices in the Magnetic Resonance Environment

### VIII. Clinical Data

The TULSA-PRO has been evaluated in prospective clinical trials, including the TACT Pivotal Study which was designed to determine the safety and effectiveness of the device according to the proposed intended use. Between September 2016 and February 2018, the TACT study enrolled 115 patients across the United States, Canada and Europe with biopsy-proven, organ-confined prostate cancer (67.0% and 33.0% of subjects had NCCN intermediate and low risk disease, respectively). All patients received primary treatment of whole-gland prostate ablation with sparing of the urethra and urinary sphincter. The median age of enrolled patients was 65

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years, with targeted prostate volume of 40 cc and ultrasound treatment delivery time of 51 minutes. A median of 97.6% of the prescribed prostate volume was heated to an ablative thermal dose with spatial ablation precision of ±1.4 mm measured on MRI thermometry during treatment.

The primary efficacy endpoint of TACT was the proportion of patients achieving a post-treatment PSA reduction ≥ 75% of their pre-treatment baseline value. The primary safety endpoint was the frequency and severity of all adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Secondary endpoints included prostate volume reduction, proportion of patients with negative biopsy, patient reported changes in quality of life (erectile, urinary and bowel function), and evaluation of multiparametric prostate MRI. Primary and secondary endpoints were assessed at 12 months after TULSA-PRO treatment, with per-protocol follow-up continuing to 5 years.

The TULSA-PRO device used to collect clinical data was developed and manufactured in accordance with requirements of ISO 13485 compliant Quality Management System. The prospective clinical studies were conducted in accordance with 21 CFR 812 regulations.

## Safety: Adverse Events

All Adverse Events (AE) were documented during the TACT study regardless of their attribution to the TULSA-PRO procedure. All AE's were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) developed by the NCI and were standardized to medical terminology using the Medical Dictionary for Regulatory Activities (MedDRA). Table 1 summarizes all AE observed during the TACT pivotal study through to the 12-month visit, regardless of severity or relation to the TULSA-PRO device or procedure. To 12 months, there was no rectal injury or fistula, and no severe urinary incontinence or erectile dysfunction. There were no Grade 4 or higher AE related or possibly related (attributable) to TULSA-PRO. There was one unrelated Grade 4 event of coronary artery disease resolved with a triple coronary artery bypass. There were 12 attributable Grade 3 AE in 9 patients (7.8%), all resolved by the 12 month follow-up. An additional 10 unrelated Grade 3 events occurred in 7 subjects, of which two were ongoing at 12 months: an upper GI bleed caused by esophageal adenocarcinoma which was resolving as of 12 months, and unrelated pelvic pain caused by a urinary stone which resolved after the 12 month visit.

The majority of attributable events were acute Grade 1 and 2 (occurring and resolving within 3 months of treatment), related to the genitourinary system.

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Urethral stenosis occurred in 3 subjects (one Grade 2 and two Grade 3, all resolved). Urinary tract infections were common and resolved with oral antibiotics in nearly all affected patients. Urinary retention occurred in 9 attributable Grade 2 events (7% of patients) and 2 attributable Grade 3 events (1.7%), all resolved with medication and prolonged catheterization up to a maximum of less than 3 months. Attributable gastrointestinal AE were limited to acute Grade 1 events and 7 acute Grade 2 events: pain/discomfort (3.5% of subjects), nausea (1.7%), and constipation (0.9%), all of which resolved within one month and could potentially be attributed to anesthesia or GI anti-spasmodic medication.

Erectile dysfunction and urinary incontinence are common events after prostate therapies. Erectile dysfunction after TULSA-PRO in the TACT study was expected due to the whole-gland nature of the ablation. Of the 52 patients (45.2%) with some erectile dysfunction immediately after TULSA-PRO treatment, 49 (42.6%) were assessed by the study investigators as attributable to TULSA-PRO, of which 41 (35.7%) were ongoing at the 12-month follow-visit: 14 patients (12.2%) had mild erectile dysfunction (Grade 1, intervention not indicated), 27 patients (23.5%) had moderate erectile dysfunction (Grade 2, intervention such as medication indicated), and no patient (0%) had severe erectile dysfunction (Grade 3, intervention such as medication not helpful) or permanent disability.

Of the 28 patients (24.3%) with some urinary incontinence immediately after TULSA-PRO treatment, 26 (22.6%) were assessed by the study investigators as attributable to TULSA-PRO, of which 12 (10.4%) were ongoing at the 12-month follow-visit: 9 patients (7.8%) had mild urinary incontinence (Grade 1, occasional, pads not indicated), 3 patients (2.6%) had moderate urinary incontinence (Grade 2, spontaneous, pads indicated), and no patient (0%) had severe urinary incontinence (Grade 3, operative intervention indicated) or permanent disability.

Ongoing attributable moderate (Grade 2) AE at 12 months included ejaculatory disorder (retrograde ejaculation, 2.6% of subjects), weak urinary stream (2.6%), urinary tract infection (1.7%), and disrupted urethra (0.9%, identified on cystoscopy).

42 ( 36.5 %)

32 ( 27.8 %)

21 ( 18.3 %)

26 ( 22.6 %)

| Adverse Event (AE) | Any occurrence, regardless<br>of attribution<br># Subjects (%) (n=115) | Subset of AE attributable to<br>TULSA-PRO<br># Subjects (%) (n=115) |
|----------------------|------------------------------------------------------------------------|---------------------------------------------------------------------|
| Total | 109 ( 94.8 %) | 101 ( 87.8 %) |
| Erectile dysfunction | 52 ( 45.2 %) | 49 ( 42.6 %) |

48 ( 41.7 %)

42 ( 36.5 %)

29 ( 25.2 %)

28 ( 24.3 %)

Haematuria Urinary tract infection

Urinary incontinence

Dysuria

Table 1: Summary of all adverse events in TACT. Number of patients with AE, any

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Image /page/10/Picture/1 description: The image shows the logo for Profound Medical Inc. The word "PROFOUND" is in large, bold, blue letters. Below that, the word "MEDICAL" is in smaller, blue letters, and to the right of that, the letters "Inc." are in even smaller, blue letters. There is a blue line going through the letters "OU" in the word "PROFOUND", with a blue dot in the middle of the line.

| Adverse Event (AE) | Any occurrence, regardless<br>of attribution<br># Subjects (%) (n=115) | Subset of AE attributable to<br>TULSA-PRO<br># Subjects (%) (n=115) |
|----------------------------------------------------|------------------------------------------------------------------------|---------------------------------------------------------------------|
| Pain/discomfort<br>(pelvic/genital/treatment area) | 27 (23.5%) | 25 (21.7%) |
| Oedema (testicular, scrotal, penile) | 27 (23.5%) | 24 (20.9%) |
| Urinary urgency | 26 (22.6%) | 25 (21.7%) |
| Catheter site pain/inflammation | 20 (17.4%) | 7 (6.1%) |
| Pain/discomfort (abdominal/anorectal) | 17 (14.8%) | 14 (12.2%) |
| Urinary frequency | 16 (13.9%) | 16 (13.9%) |
| Bladder spasm | 14 (12.2%) | 12 (10.4%) |
| Ejaculation disorder | 14 (12.2%) | 14 (12.2%) |
| Non-descriptive LUTS | 14 (12.2%) | 10 (8.7%) |
| Urinary retention | 13 (11.3%) | 10 (8.7%) |
| Urethral bleeding | 13 (11.3%) | 13 (11.3%) |
| Pain/discomfort (hip/back) | 12 (10.4%) | 9 (7.8%) |
| Urethral discharge | 11 (9.6%) | 11 (9.6%) |
| Weak urinary stream | 11 (9.6%) | 11 (9.6%) |
| Pain/discomfort (bladder/urinary tract) | 10 (8.7%) | 9 (7.8%) |
| Fatigue | 9 (7.8%) | 3 (2.6%) |
| Hypotension | 8 (7%) | |
| Nausea | 8 (7%) | 2 (1.7%) |
| Epididymitis | 7 (6.1%) | 7 (6.1%) |
| Headache | 7 (6.1%) | 2 (1.7%) |
| Debris in urine | 5 (4.3%) | 5 (4.3%) |
| Orchitis | 5 (4.3%) | 2 (1.7%) |
| Constipation | 4 (3.5%) | 2 (1.7%) |
| Dyspepsia | 4 (3.5%) | |
| Fever | 4 (3.5%) | 3 (2.6%) |
| Hypertension | 4 (3.5%) | |
| Nocturia | 4 (3.5%) | 3 (2.6%) |
| Procedural hypotension | 4 (3.5%) | |
| Libido decreased | 4 (3.5%) | |
| Inguinal hernia | 3 (2.6%) | |
| Urethral stenosis | 3 (2.6%) | 3 (2.6%) |
| Calculus urinary | 2 (1.7%) | 1 (0.9%) |
| Hydronephrosis | 2 (1.7%) | 1 (0.9%) |
| Anaemia | 1 (0.9%) | |
| Syncope | 1 (0.9%) | |
| Upper gastrointestinal haemorrhage | 1 (0.9%) | |
| Urinoma | 1 (0.9%) | 1 (0.9%) |
| Urosepsis | 1 (0.9%) | |
| Deep vein thrombosis | 1 (0.9%) | 1 (0.9%) |
| Diverticulitis | 1 (0.9%) | |
| Ileus | 1 (0.9%) | |
| Other* | 95 (82.6%) | 41 (35.7%) |

* Includes all non-serious Grade ≤ 2 events with occurrence in < 3% of all patients

# Effectiveness: Prostate Volume Reduction, PSA Reduction and Prostate Biopsy at 12 months

Evidence of effective prostate tissue ablation is provided through Prostate Volume Reduction, PSA Reduction and Prostate Biopsy at 12 months.

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## K191200 Traditional 510(k) — TULSA-PRO System

## Prostate Volume Reduction

Prostate volume reduction was measured in the TACT study demonstrating effective ablation of the prescribed prostate volume. As per protocol, the TACT study employed a central radiology core lab to measure prostate volume prior to and after treatment with TULSA-PRO, providing consistent methodology and reducing inter-observer variability. In the TACT study, 106 of the 115 patients had MR image data prior to and after TULSA (at 12 months) that were available and readable by the central radiology core lab. Based on the per-protocol assessment from a central radiology core lab, the median (IQR) perfused prostate volume of patients in TACT decreased 91.4% from 37.3 (27.2 – 47.6) cc pre-treatment to 2.8 (1.7 – 4.7) cc at 12 months on MRI. The mean and 95% confidence interval of the prostate volume reduction was 89% (87 – 91%). Given the treatment intent of whole-gland ablation with sparing of the urethra and urinary sphincter, the prostate volume reduction measurements demonstrate that the TULSA-PRO achieved effective prostate tissue ablation.

## PSA Reduction

PSA reduction and stability provide additional evidence of effective prostate tissue ablation. Reduction of PSA was observed in all patients at nadir and at 12 months. Primary endpoint of PSA reduction ≥75% was achieved in 110 of 115 (96%) patients. Mean (95% confidence interval) PSA reduction to nadir was 92% (90 – 94%). Median (IQR) PSA reduction was 95% (91 – 98%) to nadir of 0.34 (0.12 – 0.56) ng/ml. Median (IQR) PSA decreased from 6.26 (4.65 - 7.95) ng/ml to 0.53 (0.30 - 1.19) ng/ml at 1 month, remaining stable to 0.53 (0.28 – 1.25) ng/ml at 12 months.

## Prostate Biopsy at 12 months

Negative prostate biopsy outcomes provide additional evidence of effective prostate tissue ablation. Prostate histological response was evaluated through 10core prostate biopsy at 12 months, providing high sampling density of the prostate due to the significant volume reduction after TULSA-PRO treatment. Of 115 patients enrolled in the study, 4 (3.5%) did not undergo follow-up biopsy, all due to patient refusal.

Using an intent-to-treat analysis (ITT), of 115 patients enrolled in the study, 72 (63%) had a complete histological response with no evidence of any cancer (95% confidence interval: 54 – 71%). For this ITT analysis, the 4 patients who refused follow-up biopsy were considered "positive".

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# K191200 Traditional 510(k) — TULSA-PRO System

This data is consistent with the prescribed treatment plan, supports the substantial equivalence of the TULSA-PRO to its predicate, and demonstrates safety and effectiveness of the device for ablation of prostate tissue.

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Image /page/13/Picture/1 description: The image shows the logo for Profound Medical Inc. The logo is in blue and consists of the word "PROFOUND" stacked on top of the word "MEDICAL" with "Inc." to the right of the word "MEDICAL". There is a horizontal line going through the letters "OUN" in the word "PROFOUND" with a circle in the middle of the line.

#### IX. Substantial Equivalence

The Ablatherm Integrated Imaging has been selected as a predicate device to establish substantial equivalence to TULSA-PRO. Both the subject and predicate devices are High Intensity Therapeutic Ultrasound devices and are indicated for the ablation of prostate tissue. Both devices are intended for use by physicians who have completed mandatory training for safe operation of the devices. Both the subject and predicate devices are intended for prescription use and are performed as minimally invasive procedures.

Although there are differences in technological features that could impact safety or effectiveness, the safety and effectiveness of the TULSA-PRO have been demonstrated through assessment of clinical studies. The substantial equivalence is demonstrated in the Table 2.

| Table 2. Substantial equivalence table | | |
|----------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Subject Device (TULSA-PRO System) | Predicate Device (Ablatherm Integrated Imaging) |
| Manufacturer | Profound Medical Inc. | EDAP Technomed, Inc. |
| 510(k) No. | Not yet assigned | K153023 |
| Regulation Number | 21 CFR 876.4340 | 21 CFR 876.4340 |
| Product Code | PLP | PLP |
| Indications for Use | TULSA-PRO® is indicated for thermal ablation of prescribed prostate tissue, benign and malignant, using transurethral ultrasound ablation (TULSA) with in-bore real-time MRI treatment planning, monitoring, visualization, thermal dosimetry, and active temperature feedback control of thermal treatment. | The Ablatherm Integrated Imaging device is indicated for transrectal high intensity focused ultrasound (HIFU) ablation of prostate tissue. |
| Prescription Use | Yes | Yes |
| Non-surgical, Minimally invasive | Yes | Yes |
| Outpatient procedures | Yes | Yes |
| Anesthesia required | Yes | Yes |
| Physician training required | Yes | Yes |
| System Components | Main console containing electronics and | Control module, computer and peripherals. Treatment |
| | Subject Device (TULSA-PRO<br>System) | Predicate Device<br>(Ablatherm Integrated<br>Imaging) |
| | programmable hardware<br>(System<br>Electronics unit)<br>PC computer, LCD display,<br>custom ablation<br>delivery software (TDC unit)<br>Water cooling circuit (System<br>Cart, Fluid<br>Circuit)<br>Transurethral Ultrasound<br>Applicator (UA)<br>Endorectal Cooling Device<br>(ECD)<br>Positioning System<br>Disposable accessories | module, (patient support),<br>endorectal probe, cooling<br>unit,<br>probe moment assembly<br>and<br>holder, movement<br>detector,<br>ultrasound scanner,<br>Disposable accessories |
| Patient position | Head-first supine | Right lateral decubitus |
| Route of Energy Delivery | Trans-urethral | Trans-rectal |
| Prostate size limitation | Prostates up to 110cc | Not available |
| Ablation modality | High Intensity Directional<br>Ultrasound | High Intensity Focused<br>Ultrasound |
| Imaging modality for<br>localization, treatment and<br>control | MRI | Ultrasound |
| Ablation Frequency | Dual Ablation Frequency:<br>Low Frequency range: 4 - 4.8<br>MHz<br>High Frequency range: 13.4 -<br>14.4 MHz | 3.0 MHz |
| Total acoustic power | 4 W per element (low<br>frequency)<br>2W per element (high<br>frequency)<br>Max (10 elements): 40W /<br>20W | 35-48 W according<br>lesion length (19<br>to 24 mm) |
| Probe type | Linear array | Curved array |
| Ultrasound Transducer/Probe | Linear array of 10 planar<br>rectangular ultrasound<br>transducer elements with<br>individually controlled | Transducer array with<br>choice of power and focal<br>length |
| | Subject Device (TULSA-PRO<br>System) | Predicate Device<br>(Ablatherm Integrated<br>Imaging) |
| Probe Placement | Manual transurethral device<br>insertion with guidewire.<br>Probe attached to custom<br>Positioning System arm<br>mounted to MRI base plate (3-<br>axis manual adjustment).<br>Automated linear probe<br>adjustment within urethra<br>based on MR image guidance. | The endorectal probe is<br>attached to the probe<br>movement assembly on<br>the treatment module,<br>and is inserted into the<br>patient's rectum during<br>treatment. |
| Transducer<br>Movement/Ablation volume | Automated device rotation<br>using custom Positioning<br>system.<br>Transurethral probe rotates<br>360° to ablate prescribed<br>prostate volume in one<br>sweep. | Not available |
| Fusion of ultrasound with other<br>imaging modalities (DICOM) | No | No |
| Ultrasound Duty cycle | Continuous ultrasound<br>delivery | 6 seconds "on" and 4<br>seconds "off" |
| Lesion Shape | 5mm-wide directional beam<br>(candle flame shape). Ten<br>adjacent transducer elements<br>produce overlapping heating<br>pattern. Continuous volume of<br>thermal ablation is delivered. | Multiple discrete volumes<br>of thermal ablation are<br>delivered |
| Ablation planning | Sagittal, Coronal and Axial<br>planes | In transverse and<br>longitudinal planes |
| Longitudinal motion | 6.4 cm | 8.0 cm max length<br>scanning |
| Management of protocols | Close-loop control algorithm | Pre-set algorithm |

### Table 2. Substantial equivalence table

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