Symani Surgical System

DEN230032 · Mmi North America, Inc. · SAQ · Apr 5, 2024 · General, Plastic Surgery

Device Facts

• Record ID: DEN230032
• Device Name: Symani Surgical System
• Applicant: Mmi North America, Inc.
• Product Code: SAQ · General, Plastic Surgery
• Decision Date: Apr 5, 2024
• Decision: DENG
• Submission Type: Direct
• Regulation: 21 CFR 878.4963
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The Symani® Surgical System is intended for soft tissue manipulation to perform anastomosis. suturing, and ligation microsurgery techniques on small blood vessels and lymphatic ducts between 0.1 and 2.5 mm in open free-flap surgery of the breast and extremities and open lymphatic surgery of the extremities. The Symani® Surgical System is indicated for use during microsurgical procedures when use of a motion scaling function is deemed appropriate by the System is indicated for use in adults. It is intended to be used by trained physicians in an appropriate operating environment in accordance with the Instructions for Use.

Device Story

Symani Surgical System is a software-controlled, electromechanical robotic system for open microsurgery. Surgeon operates from a console using two hand-held Master Controllers to manipulate two robotic instruments at the surgical site. System replicates and scales down surgeon movements (scaling factors 7X, 10X, 12X, 20X) to provide tremor reduction and precision. Components include a console, a cart with macropositioner and two micromanipulators, and single-use, EtO-sterilized articulated instruments (needle holders, dilators). Used in OR by trained physicians alongside conventional optical or digital microscopes. System provides motion scaling and tremor reduction to assist in delicate suturing and anastomosis. Benefits include improved needle angulation accuracy and ergonomic comfort for the surgeon. Device integrates into standard surgical workflows; instruments are mechanically attached to micromanipulators and can be replaced during procedures. System does not incorporate wireless technology.

Clinical Evidence

No clinical data provided in the document. FDA requires postmarket clinical validation performance testing for both lymphovenous anastomosis and free-flap procedures to demonstrate long-term effectiveness and safety, including comparisons to manual cohorts and proficiency assessments for novice and experienced surgeons.

Technological Characteristics

Software-controlled electromechanical system; electromechanical arms with attached surgical instruments; bedside human/device interfaces; no integrated visualization. Requires electrical safety, electromagnetic compatibility, and mechanical safety testing. Patient-contacting components must be biocompatible and non-pyrogenic. Sterilization and reprocessing validation required for reusable components.

Indications for Use

Indicated for adults undergoing microsurgical procedures requiring soft tissue manipulation, anastomosis, suturing, or ligation of small blood vessels and lymphatic ducts (0.1–2.5 mm) during open free-flap surgery of the breast/extremities or open lymphatic surgery of the extremities, where motion scaling is deemed appropriate by the surgeon.

Regulatory Classification

Identification

An electromechanical system for open microsurgery is a software-controlled electromechanical system with bedside human/device interfaces and without an integrated visualization system which allows a qualified user to perform surgical techniques during open mircosurgical procedures using surgical instruments attached to an electromechanical arm.

Submission Summary (Full Text)

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### DE NOVO CLASSIFICATION REQUEST FOR SYMANI SURGICAL SYSTEM

#### REGULATORY INFORMATION

FDA identifies this generic type of device as:

Electromechanical system for open microsurgery. An electromechanical system for open microsurgery is a software-controlled electromechanical system with bedside human/device interfaces and without an integrated visualization system which allows a qualified user to perform surgical techniques during open microsurgical procedures using surgical instruments attached to an electromechanical arm.

NEW REGULATION NUMBER: 21 CFR 878.4963

CLASSIFICATION: Class II

PRODUCT CODE: SAQ

## BACKGROUND

DEVICE NAME: Symani Surgical System

SUBMISSION NUMBER: DEN230032

DATE OF DE NOVO: April 25, 2023

#### SPONSOR INFORMATION:

MMI North America, Inc. 344 Ponte Vedra Blvd. Ponte Vedra, Florida 32082

#### INDICATIONS FOR USE

The Symani® Surgical System is intended for soft tissue manipulation to perform anastomosis. suturing, and ligation microsurgery techniques on small blood vessels and lymphatic ducts between 0.1 and 2.5 mm in open free-flap surgery of the breast and extremities and open lymphatic surgery of the extremities.

The Symani® Surgical System is indicated for use during microsurgical procedures when use of a motion scaling function is deemed appropriate by the System is indicated for use in adults. It is intended to be used by trained physicians in an appropriate operating environment in accordance with the Instructions for Use.

## LIMITATIONS

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The sale, distribution, and use of the Symani Surgical System are restricted to prescription use in accordance with 21 CFR 801.109.

Safety and effectiveness of Symani Surgical System has not been established for replantation of the fingers, toes, or limbs.

Safety and effectiveness of Symani Surgical System has not been established for free-flap surgery of the head & neck and trunk.

Safety and effectiveness of Symani Surgical System has not been established in the heart, central circulatory system, central nervous system, peripheral nervous system, or the eye.

The long-term outcomes of lymphovenous anastomoses performed with the Symani System for the treatment of lymphedema have not been evaluated.

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

#### DEVICE DESCRIPTION

The Symani Surgical System is designed for open microsurgery procedures, featuring articulated and interchangeable instruments.

The surgeon manipulates the Master Controllers, which in turn drive the articulated (wristed) robotic Instruments at the operating table/site, replicating and scaling down the surgeon movements using a chosen scaling factor. Symani is used in combination with conventional surgical microscopes, either optical or digital.

Symani is composed of three main components (Figure 1):

- The Console, which is a reusable equipment and not sterile; .
- The Cart with Macropositioner and two Micromanipulators, which is a reusable equipment . and not sterile: and
- . Two articulated Instruments, which are single-use and terminally sterilized via ethylene oxide

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Image /page/2/Figure/0 description: The image shows a Symani surgical robot. The robot is white and has a robotic arm with multiple joints. The robot is on wheels, and there is a control panel next to it. The robot is designed to assist surgeons with minimally invasive surgery.

Figure 1: Main components of the Symani Surgical System (from left to right. Console, Cart with Macropositioner and two Micromanipulators, Instrument)

## Symani System Components

#### Console

The Console (Figure 2) is the main user interface to control the Instruments while in teleoperation mode. It is composed of:

- An equipped Chair for surgeon ergonomic posture .
- . Two hand-held wired Master Controllers
- A Tracking System to detect Master Controllers' motion within a defined workspace .
- . A Footswitch for activating different operating modalities

Image /page/2/Picture/9 description: The image shows a white chair with armrests and footswitch pedals. The chair has a tracking system attached to it. The chair is on wheels and has a footrest. The footswitch pedals are blue and yellow.

Figure 2: Console

## Cart, Macropositioner and Micromanipulators (CMM)

The CMM (Figure 3) primary function is to actuate two articulated Instruments replicating the surgeon's movements within the surgical workspace. It is composed of:

- · A Cart,

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- · A Macropositioner,
- . Two Micromanipulators

Image /page/3/Figure/2 description: The image shows a medical device with several labeled components. The device includes a cart for mobility, a touch screen for user interface, and an LEDs bar. It also features a macropositioner and two micromanipulators, labeled as 1 and 2, which are likely used for precise movements during medical procedures.

Figure 3: Cart with Macropositioner and Micromanipulators

## Instruments

The Instruments are single-use and are provided in sterile condition (EtO sterilized). The Instruments (Figure 4) are mechanically attached to the Micromanipulators before the surgical procedure. The attachment system allows replacement during the microsurgery procedure as needed, and removal at the end of procedure. There are 5 instruments (Table 1) and each Instrument is comprised of:

- . A backend, which incorporates transmission systems required to activate the Instrument articulated wrist and tips;
- . A rigid elongated hollow shaft, providing a connection between the distal articulated wrist and the backend;
- An articulated wrist with three degrees of freedom (DOFs) pitch, yaw, and grip; the wrist, . which is placed at the distal end of the shaft, is activated by tendons running through the hollow shaft.

Image /page/3/Picture/9 description: The image shows a surgical instrument with labels pointing to different parts. The labels indicate the backend, shaft, and wrist of the instrument. The wrist is shown in more detail in an inset image, highlighting the articulating joint and the grasping mechanism. The instrument appears to be designed for minimally invasive surgery, allowing for precise movements within the body.

Figure 4: Detailed views of Articulated Instruments

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| | | | | Table 1: List of instruments | |
|--------------------------------|----------------|--------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------|---------------------------------------|
| Name | Reference Code | Selling Code | Intended Use Description | Articulated Wrist Diameter | Pictures |
| Micro Needle Holder | INS-AaT2221 | INS-M-NH | Tips optimized for grasping/handling microsurgical sutures ranging from 8-0 to 10-0 with needles ranging from 70 to 150μm | 3.5 mm | Image: Micro Needle Holder |
| Micro Needle Holder Suture Cut | INS-AeT1221 | INS-M-NHSC | Tips optimized for grasping/handling microsurgical sutures ranging from 8-0 to 10-0 with needles ranging from 70 to 150μm and cutting the associated suture threads | 3.5 mm | Image: Micro Needle Holder Suture Cut |
| Micro Dilator | INS-ObM1221 | INS-M-DIL | Instrument with optimized tips to dilate vessels with diameter above 0.7mm and grip to handle microsurgical sutures ranging from 8-0 to 10-0 | 3.5 mm | Image: Micro Dilator |
| Supermicr 0 Needle Holder | INS-NaS2221 | INS-SM-NH | Tips optimized for grasping/handling microsurgical sutures ranging from 10-0 to 12-0 with needles ranging from 50 to 100μm | 3.0 mm | Image: Supermicr 0 Needle Holder |
| Supermier o Dilator | INS-DbS1221 | INS-SM-DIL | Instrument with optimized tips to dilate vessels with diameter ranging 0.3 to 1.0mm and grip to handle microsurgical sutures ranging from 10-0 to 12-0 | 3.0 mm | Image: Supermier o Dilator |

# De Novo Summary (DEN230032)

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## Symani Sterile Accessories

The Symani System includes several disposable accessories mainly intended to preserve the sterility of the operating field.

## Connector

The Connector's (Figure 5) main function is to physically separate the sterile Instrument from the non-sterile Symani. The Connector is mounted on the Micromanipulator after the sterile drape is placed on the Symani, and provides the means to connect the Instrument, while preserving the sterile field.

Image /page/5/Figure/4 description: The image shows a person in a clean suit holding an instrument. The instrument is connected to a micromanipulator via a connector. The person is wearing blue gloves and a white clean suit. The image is likely taken in a cleanroom environment.

Figure 5: Connector mounted onto the Micromanipulator

## Master Controller Clips

The Master Controller Clips are used to affix the Master Controller Drape to the Master Controller and to improve the ergonomics of the grasps to users (Figure 6).

Image /page/5/Picture/8 description: In the image, a pair of tweezers is being held by a hand wearing a glove. The tweezers are made of metal and have white handles. The tweezers are holding a small amount of white material. The background is a light blue color.

Figure 6: Master Controller Clip Assembled on the Master Controller and Master Controller Drape

## Master Controller Holder

The Master Controller Holder's function is to stow the Master Controllers when not in use by the surgeon. The Master Controller Holder is composed by a cup with an elastic clip, which is used to affix the holder to the seat armrest (Figure ).

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## Pouches

As an alternative to the Master Controller Holder (Figure 7), Pouches with an adhesive strip can be used to support the draped Master Controllers when not used during the surgical operation to preserve their sterility. OR staff can choose to use sterile pouches instead of the Master Controller Holders based on their preference. Sterile pouches are manufactured by 3MIM and are commercially available in US.

Image /page/6/Figure/2 description: The image contains two photos. The photo on the left shows a chair with a master controller holder attached to it. The photo on the right shows a piece of medical equipment that is covered in plastic.

Figure 7: Master Controller Holder installed onto the Chair (left) and Pouch attached to the right side of the Console Drape (right)

## Third-party Devices and Accessories

## Drapes

The Symani Surgical System is intended to be used with third-party drapes (which are provided with the Symani Surgical System) as shown in Table 2. The sterile drapes are thin, flexible plastic covers, supplied in sterile conditions. The drapes separate the sterile Instruments and the sterile field from the non-sterile parts of the system. Three drapes are used to cover the Symani CMM (Robot Drape), the Console (Console Drape) and the Master Controllers (Master Drape).

| REF | Description | 510(k) # | Sterile | Disposable |
|---------|--------------|----------|---------|------------|
| DRP-100 | Chair Drape | K101689 | Yes | Yes |
| DRP-201 | Master Drape | K101689 | Yes | Yes |
| DRP-302 | Robot Drape | K101689 | Yes | Yes |

Table 2: Third-Party Devices Provided with the Symani Surgical System

## Microscopes

The Symani Surgical System is compatible the optical surgical microscopes listed in Table 3.

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| Table 3: Compatible 3rd-Party Microscopes | |
|-------------------------------------------|----------|
| Microscope | 510(k) # |
| Zeiss KINEVO 900 | Exempt |
| Zeiss OPMI VARIO with accessories | K162991 |
| Leica M525-F50 | Exempt |
| Storz VITOM | Exempt |
| True Digital Surgery OCCIPTA | Exempt |
| Olympus ORBEYE | K190772 |

#### SUMMARY OF NON-CLINICAL/BENCH STUDIES

Non-clinical performance tests were performed to demonstrate that the Symani Surgical System will perform as anticipated for its intended use and to mitigate the risks to health as outlined below.

#### BIOCOMPATIBILITY/MATERIALS

The purpose of testing all materials for biocompatibility and pyrogenicity is to mitigate the risk of adverse tissue reactions and infections for the patient.

The instruments are external communicating devices in contact with tissue/bone/dentin for limited duration (< 24 hours). Therefore, the following tests in Table 4 were performed according to FDA's guidance document, "Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" and applicable standards:

| Test | Method | Results |
|-----------------------------------|--------------------------------------------------------------------------|-------------------|
| Cytotoxicity | ISO 10993-5:2009 and ISO 10993 12:2021 | Non-cytotoxic |
| Sensitization | ISO 10993-10:2021 and ISO 10993-12:2021 | Non-sensitizer |
| Irritation | ISO 10993-23:2021 and ISO 10993 12:2021 | Non-irritant |
| Material-mediated<br>Pyrogenicity | ISO 10993-11:2017, ISO 10993-12:2021, and USP NF<br>2022 Issue 2 par 151 | Non-pyrogenic |
| Acute Systemic Toxicity | ISO 10993-11:2017 and ISO 10993-12:2021 | Non-toxic (acute) |
| Hemocompatibility | ISO 10993-4:2017, ISO 10993-12:2021, and ASTM<br>F756-17 | Non-hemolytic |

Table 4: Summary of the Biological Safety Tests

All testing and results were considered to be adequate and met the above standards.

#### STERILITY/ REPROCESSING / PACKAGING/SHELF LIFE

The purpose of the sterility, packaging, and shelf-life evaluations were to mitigate the risk of infection for the patient.

#### Single-Use Components

The instruments and accessories are single use and provided sterile via ethylene oxide to a sterility assurance level of 106 in accordance with ISO 11135 and ISO 10993-7. The primary packaging are pouches made of uncoated high-density polyethylene (HDPE) non-woven ((0)(4) (0)(4) ], which is heat sealed together with a multi-ply biaxially oriented polyethylene

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terephthalate/polyethylene plastic laminate. The single-use components provided in sterile condition (Instruments and Accessories) and the related packaging have been tested to address requirements for both transit endurance (shipping and distribution per ASTM D4169) and shelflife stability. The package was shelf-life tested using accelerated aging in accordance with American Society of Testing and Materials ASTM F1980-07 (Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices) to achieve 24 months of shelf life. All test samples were sterilized prior to aging. The instruments and accessories functionality were also evaluated.

## Reusable Components

The Symani Surgical System's reusable components are the Cart. Macropositioner and Micromanipulators (CMM) and the Console. These components are not sterile, and they are draped before use to ensure sterility of the surgical field. Cleaning for reusable components was validated in accordance with ANSI/AAMI ST98:2022 Cleaning validation of health care products-Requirements for development and validation of a cleaning process for medical devices and FDA's guidance document, "Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling - Guidance for Industry and Food and Drug Administration Staff".

All testing and results were considered to be adequate and met the above standards.

## ELECTROMAGNETIC COMPATIBILITY AND SAFETY TESTING

The electromagnetic compatability, and electrical, mechanical, and thermal safety were evaluated to mitigate the risks of patient injury or delay of treatment.

The following testing has been performed according to FDA's Guidance, "Electromagnetic Compatibility (EMC) of Medical Devices" and the standards listed below:

- IEC 60601-1:2005/AMD1:2012 Medical electrical equipment Part 1: General . requirements for basic safety and essential performance
- IEC 60601-1-2:2014/AMD1:2020 General requirements for basic safety and essential . performance -Collateral Standard: Electromagnetic disturbances - Requirements and tests
- IEC 80601-2-77:2019 Medical electrical equipment Part 2-77: Particular requirements . for the BASIC SAFETY and essential performance of ROBOTICALLY ASSISTED SURGICAL EQUIPMENT

All testing and results were considered to be adequate and met the above standards.

## WIRELESS TECHNOLOGY

The Symani Surgical System does not incorporate wireless technology.

## SOFTWARE

The software was evaluated to mitigate the risks electrical and mechanical faults associated with device not working as intended due to the programming, and patient injury due to system

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malfunctions.

The Symani Software is organized in two main programmable systems (PESS):

- Embedded Controller Software .
- Master Controller tracking Firmware, provided by the manufacturer of the Tracking . System

The Embedded Controller Software is organized in three main subsystems:

- . A Real-Time (RT) subsystem which runs a Real-Time Operating System in the Embedded Controller
- Field programmable gate array (FPGA) firmware .
- Configuration and Calibration files stored in the Embedded Controller .

The Embedded Controller provides the computational capabilities for supporting all the elements of the Symani software. The Real-Time subsystem manages the high-level handling of the Symani State Machine, the handling of the teleoperation with Master Controller and Instrument, the control of the Symani Arms and Instruments, and the Graphical User Interface (GUI) displayed on the Touchscreen. The FPGA subsystem provides low-level measurements, safe and deterministic paths for specific critical features, and communication with Input/Output (1/0).

The Symani software has been developed in accordance with the following FDA guidance documents and standards:

- 1) General Principles of Software Validation, issued January 11, 2002
- 2) Content of Premarket Submissions for Device Software Functions, issued June 14, 2023
- 3) Off-the-Shelf Software Use in Medical Devices, issued August 11. 2023
- 4) IEC 62304 AMD 2015, Medical Device Software Software Life-Cycle Processes
- 5) ISO 14971:2019, Medical devices Application of Risk Management to Medical Devices

CDRH considers the software to need an "Enhanced Documentation Level" as outlined in the FDA guidance document "Content of Premarket Submissions for Device Software Functions" because failure or latent flaw could directly result in death or serious injury. A hazard analysis was performed to characterize software risks including device malfunction and measurement related errors. The submission contained all the elements of software documentation that demonstrate that planning, requirements, risk assessment, design reviews, traceability, change management, testing plans and results, and other aspects of software engineering for device software functions were employed, to support the conclusion that the device software function was appropriately designed, verified, and validated.

Overall, the software documentation contains sufficient detail to provide reasonable assurance that the software will operate in a manner described in the specifications. All testing and results were considered to be adequate and met the above standards.

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## CYBERSECURITY

The Cybersecurity of the Symani System has been evaluated in accordance the FDA Guidance of September 2023 "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" demonstrating compliance with section 524B of the FD&C Act.

### PERFORMANCE TESTING - BENCH

The following bench tests were performed to mitigate the risks of electrical fault, mechanical fault, and system malfunction resulting in injury to patient.

The bench tests characterize the performance and design verification for the Symani System. All applicable testing was performed with provided and third-party devices. The descriptions and results of the main performance and safety tests are summarized in Table 5.

| Test<br>Description | Objective | Acceptance criteria | Results |
|------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------|
| Accuracy | Verify Symani Surgical System<br>translational (XYZ) and orientational<br>(RPY) accuracy. | (b)(4) for each translational axis<br>Roll accuracy (b)(4)<br>Pitch and Yaw accuracy (b)(4) | PASS |
| System<br>Resolution | Verify that the system is able to<br>replicate the user translational (XYZ)<br>and orientational (RPY) motion<br>command. | XXY axes (b)(4)<br>RPY axes (b)(4) | PASS |
| Latency | Verify that the system is able to<br>replicate the user translational (XYZ)<br>and orientational (RPY) motion<br>command within the maximum<br>allowed latency. | (b)(4) | PASS |
| Repeatability | Verify that the system is able to<br>transmit the translational (XYZ)<br>Master Controller movements to<br>Instrument tip motions in a<br>reproducible manner. | (b)(4) | PASS |
| Scaling Testing | Verify that the system is able to<br>translate translational (XYZ) Master<br>Controller movements into a relative<br>displacement of the Articulated Wrist<br>along X, Y and Z axes with a settable<br>constant motion scaling down factor<br>(7X, 10X, 12X, 20X). | (b)(4) scaling down factors<br>with a (b)(4) tolerance range | PASS |
| Hold Testing | Verify that the system is able to block<br>the translational (XYZ) movements<br>of the Instrument while in Hold<br>Limited Teleoperation | (b)(4) | PASS |
| Workspace<br>Testing | Verify the translational movements<br>workspace. | Each axis shall report a workspace value<br>between (b)(4) | PASS |
| | Verify the angular movements<br>workspace. | (b)(4) | PASS |
| System Use-Life | Demonstrate that the Symani<br>Surgical System will maintain its<br>integrity and operate properly over its<br>10 year use-life. | No structural failure or malfunctions shall<br>be observed. No component shall be<br>repaired or replaced. | PASS |
| Drop testing | Verify that multiple drops of the<br>Master Controller do not affect the<br>System performances. | No impact on performances by Master<br>Controller drops. | PASS |
| Emergency Stop<br>Testing | Verify that the Instruments motion<br>will stop within a pre-defined<br>distance when the Stop button is<br>pressed either on the GUI or on the<br>Console | Motors stops at<br>(b)(4) | PASS |
| Cutting<br>Performance | Verify instruments performance in<br>cutting sutures | The Needle Holder Suture Cut instrument<br>shall allow to perform at least (b)(4)<br>consecutive micro suture cuts. | PASS |
| Stitching<br>Performance | Verify instruments stitching<br>performance | The Dilator instrument shall allow to<br>perform at least (b) consecutive stitches<br>with microsutures | |
| | | The Needle Holder and Needle Suture<br>Cut Instruments shall allow to perform at<br>least (b)(4) consecutive stitches with<br>microsutures. | |
| Grip Force | | The Micro and Supermicro Needle Holder<br>Instrument shall perform a minimum<br>gripping force of (b) | PASS |
| | Verify the instruments grip force | The Needle Holder with Cutter Instrument<br>shall have gripping force reduced of max<br>(b)(4) compared with Needle Holder<br>Instrument. | PASS |
| Grip and Cutting | Verify that the Instruments will | Reliability of 95% and confidence level of | PASS |
| Reliability<br>Needle<br>Compatibility | reliably grip and cut after aging.<br>Verify that Needle Holder allows the<br>user to firmly grasp microsurgical | 85% with grip force (b)(4)<br>Micro Needle Holder shall firmly grasp<br>needles with diameters between 150-70<br>μm. | PASS |
| | needles. | Supermicro Needle Holder shall firmly<br>grasp needles with diameters below 100<br>μm. | PASS |
| Knot Tying | | The Micro Needle Holder and Micro<br>Needle Holder Suture Cut shall allow to tie<br>knots with microsurgical suture in the<br>range of 8-0 and 10-0. | PASS |
| | Verify that the Instruments are able<br>to handle and tie knots with<br>microsurgical sutures | The Supermicro Needle Holder and<br>Supermicro Needle Holder Suture Cut<br>shall allow to tie knots with microsurgical<br>suture in the range of 10-0 and 12-0 | PASS |
| | | The Micro Dilator instrument shall allow<br>to tie knots with microsurgical suture in<br>the range of 8-0 and 10-0 | PASS |
| | | The Supermicro Dilator instrument shall<br>allow to tie knots with microsurgical<br>suture in the range of 10/0 and 12/0. | PASS |
| Structural<br>Integrity Testing | Verify the Instruments shaft can<br>withstand worst-case load bending<br>conditions | The Instruments shaft shall not break. | PASS |
| Structural<br>Integrity Testing | Verify the Instrument shaft and<br>extremities can withstand multiple<br>co-manipulation and collision<br>conditions | The Instruments shaft shall not break. | PASS |
| | Verify the Needle Holder Instrument<br>can withstand repetitive gripping<br>actions without functional or<br>structural failures | The Needle Holder shall withstand<br>repetitive gripping actions without<br>functional (grip force(b)(4) or structural<br>failures. | PASS |
| | Evaluate the Instrument's jaws<br>resistance | Instruments tips shall withstand worst-<br>case load conditions without breaking. | PASS |
| | Microscope<br>compatibility | The microscope's head and arm shall fit<br>between Micromanipulators avoiding<br>collision with the Micromanipulators and<br>Instruments | |
| Verify 3rd party microscope's<br>compatibility with Symani | | The working distance range shall be<br>adequate to have an appropriate vision of<br>the surgical site, whilst avoiding any<br>collision with Symani Instruments and<br>Micromanipulators | PASS |
| | | The user shall be able to setup the Symani<br>and the Vision System to reach the area to<br>be treated independently to the body<br>districts | |
| | | Each user involved in the surgery shall<br>have a clear vision of the operating field<br>image | |
| | | The user shall be able to manage the<br>microscope while seated at the surgical<br>console | PASS |

#### Table 3: Bench Test Summary

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## PERFORMANCE TESTING - CADAVER AND SIMULATED USE

Performance testing was completed under simulated use conditions and using a cadaver model to demonstrate that the intended anatomy could be reached and that the device can be used for needle placement during anastomosis creation.

## Cadaver Testing

## Purpose

To verify system ergonomics and usability in a scenario simulating an operating room environment.

## Methods

A cadaver lab was used to simulate several standard procedures widely used in reconstructive microsurgery. Different surgical simulations were performed to represent anatomical accesses required in high-volume microsurgical reconstructions, such as post-oncological head and neck reconstructions, breast reconstructions or post-traumatic upper and lower limb reconstructions: Transoral access, Facial artery access, Internal mammary artery access, Thoracodorsal artery

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access. Radial arterv access. Brachial plexus access, and Lower limb access. For all simulations. two robotic wristed Instruments were used: one Dilator and one Needle Holder. Tests were performed by a team composed of two expert surgeons and six residents, with the participation of MMI Clinical Engineers that provided guidance on the device use.

The following parameters were analyzed for each surgical simulation with Symani:

- . The suitability of the system architecture for each access.
- The necessity of a microscope extension tube. .
- . Any potential interference of instruments with surrounding tissues for each access.
- . Whether the depth of the instrument run is sufficient to achieve the correct depth for anatomical access and creation of anastomosis.
- The suitability of the angle of the instruments (incline) with respect to the Macropositioner . for each access.
- . The suitability of the angle of instruments with respect to each other (angle between Instruments' shafts) for each surgical access.

#### Results

The results demonstrated that the Symani architecture allows users to reach all the desired anatomical districts necessary to robotically perform reconstructive microsurgical procedures. The architectural design allows an adequate range of configurations ensuring surgeons have the same operative conditions they are used to, as well as direct manual access to the patient in the event the surgeon deems necessary.

## Simulated Use Testing

## Purpose

To assess the precision in stitch placement with the system compared to the same microsurgical tasks using manual instruments.

## Methods

20 experienced surgeons (>5 years of microsurgery practice) and 16 users with no microsurgery experience performed the needle passage task both manually and robotically for three times. The protocol replicates standard microsurgery training models, e.g., execution of basic microsurgery tasks (stitch placement and knot tying) on validated synthetic models (latex patches and silicone tubes). Distances and angles of needle entrance and exit with respect to the cut were measured through a digital microscope. Data analysis of needle passage parameters (distance and angle) has been conducted through a paired T-test, comparing the needle passage data of manual and robotic treatments for each user group.

## Results

The use of Symani was associated with greater precision (smaller difference between the right and the left distances from the cut on latex tissue) compared to manual execution [1]. The paired Ttest showed that this difference in performance was greater for experienced microsurgeons (p = 0.02) than for users with no users with no microsurgery experience (p = 0.36). The results also

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showed higher precision using Symani compared to the manual execution for angular precision (entry/exit angles relative to the vertical cut). Experienced microsurgeons had better performance on manual and robotic needle angulation than users with no microsurgery experience. This difference in performance was greater for users with no microsurgery experience (p < 0.01) than for experienced (p = 0.19) microsurgeons. In summary, the use of the Symani enabled surgeons to achieve greater precision on needle placement, with novice users benefiting from an improvement in needle angulation compared to manual. Both experienced microsurgeons and novice users had longer suture and anastomosis times when using Symani compared to manual technique.

## HUMAN FACTORS

Human Factors Testing was performed to mitigate the risks of device-specific use error that result in harm to the patient. Human Factors testing was performed in accordance with FDA's guidance document. "Applying Human Factors and Usability Engineering to Medical Devices" to demonstrate the device usability.

#### Purpose

Human factors validation was conducted to assess users' ability to use the system safely and confirm that the system satisfies the User Requirements. Further, to verify that the mitigations implemented to the Symani System following the Use-Related Risk Analysis are effective. The HF validation test sought to:

- Verify that all risks have been identified and adequately addressed. .
- . Confirm that the residual risks are minimized or acceptable.
- . Confirm that the user interface enables effective use and protects against potentially harmful use errors.

Human factors validation testing, involving 16 participant teams in the US, each comprised of 3 participants (i.e., 1 surgeon, 1 scrub nurse and 1 circulating nurse) who completed tasks collaboratively.

The usability of the Symani Surgical System was evaluated to ensure residual risk is at acceptable levels. If any new hazardous use scenarios were identified during testing, they were assessed according to the risk management process and found to be acceptable. The human factors validation test results demonstrated that the users were able to safely interact with Symani to simulate a surgical procedure and successfully complete the tasks in a setting that simulates its clinical use for reconstructive procedures.

## IN VIVO PERFORMANCE TESTING

## Animal Testing

## Purpose

To evaluate device safety and performance for the execution of an anastomosis of small vessels in the rat's femoral arteries and veins. The objectives of the animal study were to:

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- . Demonstrate the equivalence of the robotic technique to the manual technique in terms of clinical result and the effect of the intervention.
- Evaluate the patency, potential stricture formation and potential stenosis formation at the . site of the anastomosis as well as possible migration of thrombi or distal embolization to the target organs when Symani System is used to perform vascular anastomoses, compared to vascular anastomoses placed manually.

All studies were conducted in compliance with applicable requirements in the GLP regulation (21 CFR Part 58).

## Methods

A prospective, randomized, two-arm study was conducted using 24 animals and 2 experienced microsurgeons. Patency was evaluated using the "Acland milking" test after removing the microyascular clamps (TO), after 30 minutes (T30), and 28 days after surgery day. Stricture formation (narrowing) and thrombi at the site of anastomosis were evaluated at 28 days after the procedure through light microscopy, micro-CT and histology. The anastomosis time, range between the first executed stitch and the suture of the last stitch cut. was measured. Observations for morbidity, mortality, and availability of food and water were conducted daily for all animals. Clinical observations and body weights were measured daily until the day of necropsy.

#### Results

For patency, using the "Acland milking" test, at T0 and T30 there was 100% patency for the robotic and non-robotic (manual) groups. After 28 days post-intervention, there was 100% patency for the robotic and 93.8% patency for the manual group. The robotic anastomosis time was similar to the manual time for the artery and vein. Histology demonstrated significant stricture formation at 0% for robotic artery versus 13% for manual artery. Histology demonstrated significant stricture formation at 0% for robotic artery versus 13% for manual artery. Further, it showed clinically significant (occlusive) thrombus formation at 6% manually and 0% robotically. A gross evaluation showed that an artery from the manual technique, exhibited dark-red clotted blood within the lumen at the anastomosis site. No other gross abnormalities were noted. In this study, 6 rats died, and all deaths occurred under the same surgeon. Five of deaths were attributed to hemorrhage. . All of these deaths occurred during the vessel clamping procedures. The device is not used to clamp the vessels. These deaths were likely related to surgeon error. not device-related performance concerns. One procedure death was attributed to iatrogenic hyperthermia due to malfunction of the heating pad.

There are limitations to the animal study to the model and methods. The rat model has a different collateral circulation compared to humans. Further, there were limitations to the histology due to inconsistencies in where the vessel was being sampled (i.e., sectioned). Further, histology only provides a 2-dimensional representation of a 3-dimensional structure and can miss small regions of stricture or change if these are not captured during sectioning. There were also limitations with the micro-CT because of artifacts due to suturing and variable distribution of the contrast agent. Overall, the patency results demonstrated that the device can be effectively used to create a vascular anastomosis.

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## Clinical Testing Overview

## Purpose/Objectives

The Symani study provides evidence of the safety and effectiveness of the Symani Surgical System when used to assisted microsurgical anastomosis in Free Flap transfer and Lymphatic surgery.

## Study Design

The Symani study is an OUS, prospective, single arm, multicenter, post-market clinical follow-up (PMCF) study designed to evaluate the safety and effectiveness of the Symani System when used to assist microsurgical anastomoses in a real-world setting. The Symani Study allows for the addition of retrospective data collection to the Symani study by means of a dedicated protocol addendum. The postmarket clinical follow-up registry in Europe was established in 2021. Specifically, the retrospective patients are those who meet the Inclusion and Exclusion Criteria for Symani study whose microsurgical reconstructive procedures were performed prior to the study initiation at the site.

#### Duration

The Symani Study analysis includes follow-up through 30 days.

#### Inclusion Criteria

To be eligible to participate in the Symani study, individuals were required to meet all the following criteria:

- 1. Male and female patients aged >18
- 2. Patients who need a reconstructive procedure and a microsurgical reconstruction is deemed the best option by the plastic, orthopedic or other surgeon in response to a postoncological, post-traumatic or congenital tissue defect or to treat lymphedema.
- 3. Patients who have been selected by the PI at the Clinical Center as appropriate candidates for treatment with Symani System in accordance with the IFU.
- 4. Subjects who fit the criteria to perform surgery requiring reconstructions using free flaps. replantation, lymphatic reconstructions.
- 5. Subjects who agree to have the surgery and the anesthesia.
- Subjects who voluntarily decide to participate in this study with the surgery performed 6. with the aid of the Symani System and sign the Informed Consent Form.

## Exclusion Criteria

Individuals were excluded from participating in the Symani study if any of the following criteria were met:

- 1. Subiects who have bleeding or coagulation disorders in the past or present.
- 2. Any criteria that preclude prolonged anesthesia.
- 3. History of anaphylaxis or severe complicated allergy symptoms.
- 4. Clinically significant cardiovascular, digestive, respiratory, endocrine, or central nervous system disorders or previous mental disorders that may significantly affect the data collection or the ability to comply with the protocol.
- 5. Evidence or history of autoimmune disease or compromised immune system.
- 6. Participation in another clinical trial within 4 weeks prior to participation in the study.
- 7. Subjects belonging to vulnerable populations or ineligible to participate for other reasons

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by the PI at a Clinical Center.

- 8. Subjects with pacemaker.
The patients selected for the retrospective data collection were those who met the Inclusion and Exclusion Criteria for Symani study whose microsurgical reconstructive procedures were performed prior to the study initiation at the site.

### Follow-up

Patients were enrolled, underwent surgery, and had assessments made at regular intervals (perioperatively, day 1, day 4, day 14, and day 30).

Free-Flap Surgery of Breast and Extremities

## Sample Size

93 evaluable patients were included in the analysis.

#### Study Endpoints

The following endpoints were used for the granting descision based on the device's intended use.

Effectiveness endpoints include the following:

- Intraoperative anastomosis patency .
- . Robotic usage time
- . Rate of intra-operative approach changes from robotic to manual

Safety endpoints include the following:

- Freedom from device related serious adverse events prior to discharge .
- . Freedom from device-related adverse events through discharge.
- All adverse events, regardless of device relatedness, reported within 30 days post initial or . revision procedure.
- . Anastomosis-specific reoperation rate through 3 days
- All-cause readmission rates through 30 days .
- . All-cause mortality rate through 30 days

## These other endpoints were evaluated but were not the basis the granting.

## Effectiveness endpoints include the following:

- Free flap viability at discharge .
- Free flap survival at 30 days either after the first attempt or perioperative revision, for patients . with at least one robotic anastomosis.
- . Operative time

## Safety endpoints include the following:

- All-cause reoperation rate through 30 days .

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Free-flap survival at 30 days and all-cause reoperation rate through 30 days were compared to the UK National Flap registery. These endpoints, however, were not used for making the granting descision as many factors outside of creating the anastomosis contribute to the flap survival rate and reoperation rate at 30 daysFree-flap survival at 30 days and all-cause reoperation rate through 30 days were compared to the UK National Flap registery. These endpoints, however, were not used for making the granting descision as many factors outside of creating the anastomosis contribute to the flap survival rate and reoperation rate at 30 days.

## Free-Flap Transfer Results

Table 6 summarizes the patient demographics for the clinical study for free-flap procedures. Table 7 reports the disposition of patients in Free-Flap procedures.

| Characteristic | Statistics | Breast | Extremities |
|----------------------------------------------|--------------|---------------------|--------------------|
| Demographics | | | |
| Age (years) | Mean (SD); N | 54.1 (10.6); 22/22 | 55.4 (17.5); 30/30 |
| Gender | - | - | - |
| Male | n (%); N | 0; 0/24 | 67.7; 21/31 |
| Female | n (%); N | 100; 24/24 | 32.3; 10/31 |
| Race | - | - | - |
| Caucasian | n (%); N | 100; 22/22 | 100; 28/28 |
| Black | n (%); N | 0; 0/22 | 0; 0/28 |
| Asian | n (%); N | 0; 0/22 | 0; 0/28 |
| Other | n (%); N | 0; 0/22 | 0; 0/28 |
| Height (cm) | Mean (SD); N | 0; 0/22 | 172.6 (9.7); 31/31 |
| Weight (kg) | Mean (SD); N | 167.0 (5.77); 22/22 | 81.4 (16.2); 31/31 |
| BMI | Mean (SD); N | 25.9 (4.0); 19/19 | 27.4 (5.2); 30/30 |
| Pre-operative co-existing conditions/disease | | | |
| Pre-operative<br>radiotherapy | n (%); N | 70.8; 17/24 | 19.4; 3/31 |
| Pre-operative<br>chemotherapy | n (%); N | 75; 18/24 | 9.7; 3/31 |
| Smoking now/past | n (%); N | 40.9; 2/22 | 50; 15/30 |
| Hypertension | n (%); N | 25; 6/25 | 42; 13/31 |
| Pulmonary disease | n (%); N | 4.2; 1/24 | 3.2; 1/31 |
| Diabetes | n (%); N | 4.2; 1/24 | 19.4; 6/31 |
| Ischaemic heart disease | n (%); N | 4.2; 1/24 | 19.4; 6/31 |
| Alcohol consumption<br>over limits | n (%); N | 0; 0/23 | 0; 0/31 |
| Steroids | n (%); N | 0; 0/24 | 6.5; 2/31 |

Table 6: Free-Flap Clinical Study Demographics in the Breast and Extremities

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| Characteristic | Statistics | Breast | Extremities |
|--------------------------------------------------------|------------|-------------|-------------|
| Extra-cardiac<br>arteriopathy | n (%); N | 0; 0/21 | 9.7; 3/31 |
| BMI | - | - | - |
| <20 | n (%); N | 10.5; 2/19 | 3.3; 1/30 |
| 20 to <25 | n (%); N | 31.6; 6/19 | 33.3; 10/30 |
| 25 to <30 | n (%); N | 36.8; 7/19 | 43.3; 13/30 |
| 30 to <35 | n (%); N | 21.1; 4/19 | 10; 3/30 |
| ≥ 35 | n (%); N | 0; 0/19 | 10; 3/30 |
| American Society of<br>Anesthesiologist Score<br>(ASA) | - | - | - |
| 1 | n (%); N | 12.5; 3/20 | 17.9; 5/28 |
| 2 | n (%); N | 83.3; 20/24 | 46.4; 13/28 |
| 3 | n (%); N | 4.2; 1/24 | 35.7; 10/28 |
| 4 | n (%); N | 0; 0/24 | 0; 0/28 |

Note: There was one patient with both free flap and LVA procedures were done concomitantly. Note: For some patients the information is not available. The table reports the available information.

Table 7: Disposition of Patients in Free-Flap Procedures

| | Breast | | | Extremities | | |
|--------------------------------------------------------------------------|------------------------------------------------|------------------------------------------------|--------------------------------------------|------------------------------------------------------------|-----------------------------------------------------------|--------------------------------------------|
| | All Participants | Prospective | Retrospective | All Participants | Prospective | Retrospective |
| All Enrolled Set<br>(AES) | 25 | 13 | 12 | 31 | 22 | 9 |
| Full Analysis set<br>(FAS) | 24<br>Excluded N=1<br>(Manual sutures<br>only) | 12<br>Excluded N=1<br>(Manual<br>sutures only) | 12 | 31 | 22 | 9 |
| Free flap<br>procedures included<br>primary<br>effectiveness<br>analysis | 17 | 7 | 10 | 21 | 13 | 8 |
| Procedures<br>excluded from<br>primary<br>effectiveness<br>analysis | N=7<br>no follow-up at<br>>=23 days N=7 | N=5<br>no follow-up at<br>>=23 days N=5 | N=2<br>no follow-up at<br>>=23 days N=2 | 10<br>no follow-up at<br>>=23 days N=8<br>Buried flap: n=2 | 9<br>no follow-up at<br>>=23 days N=7<br>Buried flap: n=2 | N=1<br>no follow-up at<br>>=23 days N=1 |
| Safety Set (SS) | Equivalent to FAS | Equivalent to FAS | Equivalent to<br>FAS | Equivalent to<br>FAS | Equivalent to<br>FAS | Equivalent to<br>FAS |
| Study completion<br>status | Completed: 18<br>Missing: 0<br>Withdrawn: 7 | Completed: 9<br>Missing: 0<br>Withdrawn: 4 | Completed: 9<br>Missing: 0<br>Withdrawn: 3 | Completed: 24<br>Missing: 0<br>Withdrawn: 7 | Completed: 17<br>Missing: 0<br>Withdrawn: 5 | Completed: 7<br>Missing: 0<br>Withdrawn: 2 |

Table 8: Summarizes the vessel diameter distribution for free flap surgery.

Table 8: Free Flap Vessel Diameter Distribution in the breast and Extremities

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| Vessel<br>Diameter | Breast | | Extremities | |
|--------------------|------------------------------------|------------|------------------------------------|------------|
| | Number of<br>anastomoses<br>(N=24) | Percentage | Number of<br>anastomoses<br>(N=66) | Percentage |
| ≤ 0.5 mm | 0 | 0% | 0 | 0% |
| 0.6 - 1.0 mm | 2 | 8.3% | 15 | 22.7% |
| 1.1 - 1.5 mm | 3 | 12.5% | 23 | 34.8% |
| 1.6 - 2 mm | 5 | 20.8% | 12 | 18.2% |
| 2.1 - 2.5 mm | 9 | 37.5% | 8 | 12.1% |
| > 2.5 mm | 5 | 20.8% | 8 | 12.1% |

## Effectiveness Results:

Intra-operative patency at first attempt is presented in Error! Reference source not found .. In these procedures if patency is not achieved on the first attempt the anastomosis is revised in the index procedure until patency is achieved.

| Site | Number of<br>anastomoses | Number<br>patent | Patency<br>estimate | 95% CI |
|-------------|--------------------------|------------------|---------------------|-----------------|
| Extremities | 44 | 40 | 90.9% | [78.3%, 97.5%] |
| Breast | 24 | 24 | 100% | [85.8%, 100.0%] |

Table 10: Intra-operative Anastomosis Patency at first attempt

Notes: All confidence intervals are constructed using exact methods in SAS PROC FREQ

The suturing time are shown in Table. The rate of intra-operative approach changes from robotic to manual is in Table 12. The outcome measure is based on the response to the Case Report Form question, "Did you experience any system technical issues resulting in unplanned return to conventional suturing." The subset of data used for this secondary effectiveness endpoint where the answer was "No" but the number of robotic sutures was missing, the dataset was excluded from the analysis. None of the device related issues that resulted in the user changing from robotic to manual resulted in revision of the anastomosis following the index procedure.

Table 11: Suturing time reported as mean (standard deviation) from the "all enrolled data set".

| | Number of<br>anastamoses | Anastomosis<br>procedure<br>time (mins) | Number of sutures/<br>anastamoses (n) | Average time per<br>suture (mins) |
|-----------------------------|--------------------------|-----------------------------------------|---------------------------------------|-----------------------------------|
| Breast | | | | |
| Only robotic<br>anastomoses | 8 | 25.0<br>(6.98) | 7.6 (0.52) | 3.28 (0.783) |

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| | Number of<br>anastamoses | Anastomosis<br>procedure<br>time (mins) | Number of sutures/<br>anastamoses (n) | Average time per<br>suture (mins) |
|------------------------------------------------------|--------------------------|-----------------------------------------|-------------------------------------------|-----------------------------------------------|
| Hybrid: Both<br>robotic and<br>manual<br>anastomoses | 4 | 32.5 (14.53) | Robotic: 8.0 (0.82)<br>Manual: 1.8 (0.96) | Robotic: 3.27 (1.288)<br>Manual: 4.00 (2.449) |
| Only manual<br>anastomoses | 6 | 18.3<br>(4.41) | 8.3 (0.52) | 2.19 (0.499) |
| Extremities | | | | |
| Only robotic<br>anastomoses*# | 30 | 38.0<br>(11.61) | 8.5 (2.62) | 4.28 (1.320) |
| Hybrid: Both<br>robotic and<br>manual<br>anastomoses | 5 | 49.2 (12.50) | Robotic: 6.6 (3.36)<br>Manual: 4.8 (3.11) | Robotic: 6.20 (3.109)<br>Manual: 3.24 (1.714) |
| Only manual<br>anastomoses | 13 | 40.7 | 9.7 (2.36) | 4.02 (1.333) |

* Some of the manual sutures were not recorded so the "only robotic" group may not be all robotic anastomoses #Some robotic sutures were not recorded

Table 12: Intraoperative Approach Change for Free-Flap by Anatomical Site

| Site | Number of changes | Percentage |
|-------------------|-------------------|------------|
| Upper/lower limbs | 4/36 | 11.1% |
| Breast | 1/13 | 7.7% |

## Safety Results:

The 3-day anastomosis specific reoperation rate is a clinical risk to the anastomosis in free flap surgery (Table 13). This is the timeframe the anastomosis typically fails and needs a revision. In the extremities cohort there was one reoperation (1/31; 3.23%) done within 3 days to revise the anastomosis due to venous congestion. For this patient intraoperative patency was achieved on the first attempt.

Table 13: Reoperation Rates reported as mean percentage with the 95% confidence interval

| Site | 3-day Anastomosis specific Reoperation Rates |
|-------------|----------------------------------------------|
| Extremities | 3.23%<br>[0.1%, 16.7%] |
| Breast | 0%<br>[0.00%, 14.8%] |

*Kaplan-Meier (KM) product limit analysis was undertaken on this data.

There were 10 serious adverse events recorded in the clinical database which consisted of

{22}------------------------------------------------

hematoma, flap necrosis, and thrombosis (Table ). There were no serious device related adverse events. There was one non-serious device related adverse event resulting in tissue injury. This was related to the "Grip Release Mode" feature, which becomes available when teleoperation is interrupted while the Instrument tips are squeezed. The function allowed the user to open the instrument's tips before re-entering teleoperation. This feature that contributed to this injury was removed from the device. An additional analysis was conducted evaluating it the adverse event (i.e., thrombosis, necrosis) lead to revision of the anastomosis after the index procedure. There was no adverse events leading to revision of the anastomosis.

| Site | All Adverse<br>Events | Serious Adverse<br>Events | Device Related<br>Adverse Events | Device Related<br>Serious Adverse<br>Events |
|-------------|-----------------------|---------------------------|----------------------------------|---------------------------------------------|
| Extremities | 12.9%, 4/31 | 12.9%, 4/31 | 3.2%, 1/31 | 0%, 0/31 |
| Breast | 25%, 6/24 | 25%, 6/24 | 0%, 0/24 | 0%, 0/24 |

Table 14: Adverse Event Rates through 30 days

Other safety endpoints captured are shown in Table

Table 4: Other Safety Endpoints as mean percentage with the 95% confidence interval

| Safety Endpoints | Extremities | Breast |
|-------------------------------------------------|----------------------|----------------------|
| All-cause readmission rates through 30<br>days* | 0.0% (0.0%,<br>0.0%) | 0.0% (0.0%,<br>0.0%) |
| All-cause mortality rate through 30 days* | 0.0% (0.0%,<br>0.0%) | 0.0% (0.0%,<br>0.0%) |

*Kaplan-Meier Kaplan-Meier (KM) product limit analysis was undertaken on this data

## Lymphatic Surgery in Lymphedema

## Lymphatic Surgery Results

#### Sample Size

70 evaluable patients were included in the analysis.

## Study Endpoints

The following endpoints were used for the granting decision based on the device's intended use.

Effectiveness endpoints include the following:

- Intraoperative anastomosis patency .
- Robotic usage time .
- . Rate of intra-operative approach changes from robotic to manual

Safety endpoints include the following:

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- . Freedom from device related serious adverse events prior to discharge
- . Freedom from device-related adverse events through discharge.
- . All adverse events, regardless of device relatedness, reported within 30 days post initial or revision procedure.
- All-cause reoperation rate through 30 days .
- . All-cause readmission rates through 30 days
- All-cause mortality rate through 30 days .

Table 16 summarizes the patient demographics for the clinical study for lymphatic surgery. Table 17 reports the disposition of patients in lymphatic surgery. The data is divided into upper and lower extremities due to success rates largely depending on anatomical location in lymphatic surgery.

| Characteristic | Statistics | Upper<br>Extremities | Lower<br>Extremities |
|------------------------------------|--------------|----------------------------------------------|----------------------|
| | Demographics | | |
| Age (years) | Mean (SD); N | 54.3 (10.9); 35/35 | 48.7 (13.1); 38/3 |
| Gender | | | |
| Male | n (%); N | 5.7; 2/35 | 28.9; 11/38 |
| Female | n (%); N | 94.3; 33/35 | 71.1; 27/38 |
| Race | | | |
| Caucasian | n (%); N | 97.1; 34/35 | 86.8; 33/38 |
| Black | n (%); N | 0.0; 0/35 | 14.3; 5/35 |
| Asian | n (%); N | 0.0; 0/35 | 0.0; 0/38 |
| Other | n (%); N | 2.9; 1/35 | 0.0; 0/38 |
| Height (cm) | Mean (SD); N | 163.7 (7.8); 35/35 | 169.4 (9.0); 38/3 |
| Weight (kg) | Mean (SD); N | 67.4 (13.1); 35/35 | 75.0 (16.3); 38/3 |
| BMI | Mean (SD); N | 25.2 (4.5); 35/35 | 26.1 (5.4); 38/38 |
| | | Pre-operative co-existing conditions/disease | |
| Pre-operative<br>radiotherapy | n (%); N | 45.7; 16/35 | 13.2; 5/38 |
| Pre-operative<br>chemotherapy | n (%); N | 62.9; 22/35 | 7.9; 3/38 |
| Smoking now/past | n (%); N | 31.4; 11/35 | 29.7; 11/37 |
| Hypertension | n (%); N | 20.0; 7/35 | 28.9; 11/38 |
| Pulmonary disease | n (%); N | 11.4; 4/35 | 7.9; 3/38 |
| Diabetes | n (%); N | 2.9; 1/35 | 2.6; 1/38 |
| Ischaemic heart disease | n (%); N | 0.0; 0/35 | 0.0; 0/38 |
| Alcohol consumption<br>over limits | n (%); N | 8.6; 3/35 | 0.0; 0/37 |
| Steroids | n (%); N | 5.7; 2/35 | 5.3; 2/38 |

Table 16: LVA Clinical Study Demographics

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| Characteristic | Statistics | Upper<br>Extremities | Lower<br>Extremities |
|-------------------------------|------------|----------------------|----------------------|
| Extra-cardiac<br>arteriopathy | n (%); N | 2.9; 1/35 | 0.0; 0/38 |
| BMI | - | - | - |
| <20 | n (%); N | 17.1; 6/35 | 13.2; 5/38 |
| 20 to <25 | n (%); N | 34.3; 12/35 | 26.3; 10/38 |
| 25 to <30 | n (%); N | 28.6; 10/35 | 36.8; 14/38 |
| 30 to <35 | n (%); N | 20.0; 7/35 | 18.4; 7/38 |
| ≥ 35 | n (%); N | 0.0; 0/35 | 5.3; 2/38 |
| ASA | - | - | - |
| 1 | n (%); N | 8.8; 3/34 | 28.9; 11/38 |
| 2 | n (%); N | 88.2; 30/34 | 65.8; 25/38 |
| 3 | n (%); N | 2.9; 1/34 | 5.3; 2/38 |
| 4 | n (%); N | 0.0; 0/34 | 0.0; 0/38 |
| Lymphedema stage | - | - | - |
| 0 | n (%); N | 25.7; 9/35 | 0.0; 0/35 |
| 1 | n (%); N | 5.7; 2/35 | 7.9; 3/38 |
| 2 | n (%); N | 65.7; 23/35 | 86.8; 33/38 |
| 3 | n (%); N | 2.9; 1/35 | 5.3; 2/38 |

Note: There were two patients with both free flap and LVA procedures. 3 patients where excluded from the analysis due to having only manual sutures.

Note:. For some patients the information is not available. The table reports the available information.

| | All Participants | Prospective N=52 | | Retrospective N=21 | |
|-------------------------|------------------------------------------------|------------------------------------------------|------------------------------------------------|------------------------------------------------|-------------------|
| | | Upper Extremities | Lower Extremities | Upper Extremities | Lower Extremities |
| All Enrolled Set (AES) | N=73 | N=24 | N=28 | N=11 | N=10 |
| Full Analysis set (FAS) | N=70<br>Excluded: n=3<br>(Manual sutures only) | N=23<br>Excluded: n=1<br>(Manual sutures only) | N=27<br>Excluded: n=1<br>(Manual sutures only) | N=10<br>Excluded: n=1<br>(Manual sutures only) | N=10 |
| Safety Set | Equivalent to FAS | Equivalent to FAS | Equivalent to FAS | Equivalent to FAS | Equivalent to FAS |

## Table 17: Disposition of Patients for Lymphatic Surgery

Table 18 summarizes the vessel diameter for lymphatic surgery.

Table 18: Lymphatic Vessel Diameter Distribution of LVA Cases

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| Vessel Diameter | Number of<br>anastomoses<br>(N=132) | Perc…