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 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

AI/ML Overview

Here's a detailed breakdown of the acceptance criteria and the study that proves the Symani Surgical System meets them, based on the provided text:

Overview of Device and Intended Use:

The Symani Surgical System is an electromechanical system for open microsurgery, specifically 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). Its primary indications are in open free-flap surgery of the breast and extremities and open lymphatic surgery of the extremities for adults. It's designed to provide motion scaling and tremor reduction, assisting trained physicians in an appropriate operating environment.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Symani Surgical System are primarily derived from the "Special Controls" section and the "Performance Testing - Bench" table (Table 5). The reported device performance is indicated as "PASS" for all listed bench tests.

Acceptance Criteria Category	Specific Criterion (from "Special Controls" or "Performance Testing - Bench")	Reported Device Performance (Table 5)
Bench/Performance Testing
Accuracy (Translational & Orientational)	(b)(4)* for each translational axis, Roll accuracy (b)(4), Pitch and Yaw accuracy (b)(4)	PASS
System Resolution	XXY axes (b)(4), RPY axes (b)(4)	PASS
Latency	(b)(4)*	PASS
Repeatability	(b)(4)*	PASS
Scaling Testing	(b)(4)* scaling down factors with a (b)(4)* tolerance range	PASS
Hold Testing	(b)(4)*	PASS
Workspace Testing (Translational)	Each axis shall report a workspace value between (b)(4)*	PASS
Workspace Testing (Angular)	(b)(4)*	PASS
System Use-Life	No structural failure or malfunctions shall be observed. No component shall be repaired or replaced.	PASS
Drop Testing (Master Controller)	No impact on performances by Master Controller drops.	PASS
Emergency Stop Testing	Motors stops at (b)(4)*	PASS
Cutting Performance	The Needle Holder Suture Cut instrument shall allow to perform at least (b)(4)* consecutive micro suture cuts.	PASS
Stitching Performance (Dilator)	The Dilator instrument shall allow to perform at least (b) consecutive stitches with microsutures.	PASS
Stitching Performance (Needle Holder)	The Needle Holder and Needle Suture Cut Instruments shall allow to perform at least (b)(4)* consecutive stitches with microsutures.	PASS
Grip Force (Micro/Supermicro NH)	The Micro and Supermicro Needle Holder Instrument shall perform a minimum gripping force of (b)*.	PASS
Grip Force (NH with Cutter)	The Needle Holder with Cutter Instrument shall have gripping force reduced of max (b)(4)* compared with Needle Holder Instrument.	PASS
Grip and Cutting Reliability	Reliability of 95% and confidence level of 85% with grip force (b)(4)*	PASS
Needle Compatibility (Micro NH)	Micro Needle Holder shall firmly grasp needles with diameters between 150-70 μm.	PASS
Needle Compatibility (Supermicro NH)	Supermicro Needle Holder shall firmly grasp needles with diameters below 100 μm.	PASS
Knot Tying (Micro NH/NHSC)	The Micro Needle Holder and Micro Needle Holder Suture Cut shall allow to tie knots with microsurgical suture in the range of 8-0 and 10-0.	PASS
Knot Tying (Supermicro NH/NHSC)	The Supermicro Needle Holder and Supermicro Needle Holder Suture Cut shall allow to tie knots with microsurgical suture in the range of 10-0 and 12-0.	PASS
Knot Tying (Micro Dilator)	The Micro Dilator instrument shall allow to tie knots with microsurgical suture in the range of 8-0 and 10-0.	PASS
Knot Tying (Supermicro Dilator)	The Supermicro Dilator instrument shall allow to tie knots with microsurgical suture in the range of 10/0 and 12/0.	PASS
Structural Integrity (Shaft Bending)	The Instruments shaft shall not break.	PASS
Structural Integrity (Shaft Co-manipulation/Collision)	The Instruments shaft shall not break.	PASS
Structural Integrity (Needle Holder Repetitive Gripping)	The Needle Holder shall withstand repetitive gripping actions without functional (grip force (b)(4)*) or structural failures.	PASS
Structural Integrity (Instruments Jaws Resistance)	Instruments tips shall withstand worst-case load conditions without breaking.	PASS
Microscope Compatibility (Head and Arm Fit)	The microscope's head and arm shall fit between Micromanipulators avoiding collision with the Micromanipulators and Instruments.	PASS
Microscope Compatibility (Working Distance)	The working distance range shall be adequate to have an appropriate vision of the surgical site, whilst avoiding any collision with Symani Instruments and Micromanipulators.	PASS
Microscope Compatibility (Setup/Vision)	The user shall be able to setup the Symani and the Vision System to reach the area to be treated independently to the body districts. Each user involved in the surgery shall have a clear vision of the operating field image. The user shall be able to manage the microscope while seated at the surgical console.	PASS
Clinical Performance (Effectiveness)
Intraoperative patency (Free-Flap)	Extremities: 90.9% (95% CI: [78.3%, 97.5%])	Achieved (90.9% - 100%)
	Breast: 100% (95% CI: [85.8%, 100.0%])
Intraoperative patency (Lymphatic)	Upper Extremity: 96.7% (95% CI: [88.5%, 99.6%])	Achieved (94.3% - 96.7%)
	Lower Extremity: 94.3% (95% CI: [86.0%, 98.4%])
Rate of intra-operative approach changes from robotic to manual	Upper/lower limbs (Free-Flap): 11.1% (4/36)	Achieved (7.7% - 11.1%)
	Breast (Free-Flap): 7.7% (1/13)
	Upper Extremity (Lymphatic): 6.7% (4/60)
	Lower Extremity (Lymphatic): 5.6% (4/71)
Clinical Performance (Safety)
Freedom from device related serious adverse events prior to discharge	Extremities (Free-Flap): 0% (0/31)	Achieved (0%)
	Breast (Free-Flap): 0% (0/24)
	Upper Extremities (Lymphatic): 0% (0/33)
	Lower Extremities (Lymphatic): 0% (0/37)
3-day anastomosis specific reoperation rate	Extremities (Free-Flap): 3.23% (95% CI: [0.1%, 16.7%]) - Lower than literature [3]	Achieved (0% - 3.23%)
	Breast (Free-Flap): 0% (95% CI: [0.00%, 14.8%])
	Lymphatic (30-day reoperation rate): 0.00% (95% CI: [0.00%,0.00%])

*Note: "(b)(4)" indicates redacted proprietary information, implying the specific numerical criteria were defined and met but are not publicly disclosed in this document.

2. Sample Sizes and Data Provenance

The primary clinical evidence for this device comes from a multicenter clinical study and a cadaver/simulated use study.

Clinical Study:
- Sample Size:
  - Free-Flap Procedures: 93 evaluable patients.
  - Lymphatic Surgery: 70 evaluable patients.
  - Total: 163 evaluable patients.
- Data Provenance: The Symani study is an OUS (Outside US), prospective, single-arm, multicenter, post-market clinical follow-up (PMCF) study. It also allowed for retrospective data collection. This indicates data from European centers ("6 European centers" mentioned in Commercial Data and Literature section). Therefore, the data provenance is European (OUS) and a mix of retrospective and prospective collection.
Cadaver Testing: Not specified in terms of sample size for cadavers, but "several standard procedures" were simulated.
Simulated Use Testing: 20 experienced surgeons (>5 years of microsurgery practice) and 16 users with no microsurgery experience participated.

3. Number of Experts and Qualifications for Ground Truth

Cadaver Testing: "a team composed of two expert surgeons and six residents" participated. Their specific qualifications (e.g., years of experience) are not detailed beyond "expert surgeons."
Simulated Use Testing: "20 experienced surgeons (>5 years of microsurgery practice)" and "16 users with no microsurgery experience." Their input was used to assess precision in stitch placement by measuring distances and angles. This serves as a form of ground truth for performance comparison.
Clinical Studies: The "ground truth" for clinical effectiveness and safety endpoints (e.g., anastomosis patency, adverse events, reoperation rates) was based on direct observation and clinical assessment by the participating trained physicians (surgeons) and potentially study staff at the multicenter sites. The study design does not specify adjudication by independent experts for these clinical outcomes, but rather the direct clinical results.

4. Adjudication Method for the Test Set

Clinical Study (Test Set/Clinical Data): The document does not explicitly describe an independent adjudication method (e.g., 2+1, 3+1 consensus) for the clinical outcomes in the human clinical study. The intraoperative patency and adverse events are reported as direct outcomes from the clinical settings. Anastomosis revisions, for example, were performed by the operating surgeon if patency was not achieved on the first attempt.
Simulated Use Testing: Data analysis of needle passage parameters (distance and angle) was conducted through a paired T-test. The measurements were taken through a digital microscope, implying a quantitative, objective assessment rather than subjective expert consensus requiring adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No formal Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with AI vs. without AI assistance was reported. The device is a surgical system, not an AI-assisted diagnostic or imaging interpretation tool.

However, a simulated use study did compare the precision of stitch placement with the system (robotic) versus manual instruments.

Comparison: Use of Symani vs. manual execution.
Effect Size/Performance Improvement:
- Precision (stitch placement): Use of Symani was associated with greater precision (smaller difference between right and left distances from the cut on latex tissue) compared to manual execution.
  - Experienced microsurgeons: p = 0.02 (statistically significant improvement).
  - Users with no microsurgery experience: p = 0.36 (no statistically significant difference, but trend suggests improvement).
- Angular Precision: Higher precision using Symani for angular precision (entry/exit angles relative to the vertical cut).
  - Users with no microsurgery experience: p < 0.01 (statistically significant improvement).
  - Experienced microsurgeons: p = 0.19 (no statistically significant difference).
- Conclusion: The Symani system enabled greater precision in needle placement, with novice users benefiting significantly in needle angulation.
Trade-off: Both experienced and novice users had longer suture and anastomosis times when using Symani compared to the manual technique.

6. Standalone (Algorithm Only) Performance

The concept of "standalone" performance typically applies to algorithms that autonomously make a decision. The Symani Surgical System is an electromechanical device operated by a human surgeon. Therefore, a "standalone (i.e. algorithm only without human-in-the-loop performance)" study would not be applicable, as the system always requires a human operator for its intended use. Performance is inherently coupled with the human operator.

7. Type of Ground Truth Used

Bench Testing: Engineering specifications and direct physical measurements (e.g., accuracy, resolution, latency, force, structural integrity).
Cadaver Testing: Expert judgment and qualitative assessment of system ergonomics and usability in a simulated OR environment.
Simulated Use Testing: Quantitative measurements of needle passage parameters (distance and angle) using a digital microscope on synthetic models, serving as objective ground truth for precision comparisons.
Animal Testing: Patency evaluated by "Acland milking" test, and stricture/thrombi formation evaluated by light microscopy, micro-CT, and histology – these pathology-based methods serve as objective ground truth.
Clinical Studies: Intraoperative patency (clinical observation by the surgeon), adverse events (reported clinical occurrences), reoperation rates (clinical outcomes), and other clinically observed parameters. This is effectively clinical outcomes data and direct surgeon observation as ground truth.

8. Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of an AI/ML algorithm that is trained on data. This device is an electromechanical system, not an AI diagnostic tool that learns from a dataset.

However, if "training set" refers to the data used for non-clinical performance characterization or design verification, the samples used were:

Bench Tests: Not explicitly stated as "sample sizes" but rather as tests performed on the system.
Cadaver Testing: Number of cadavers not specified, but multiple simulations were performed.
Simulated Use Testing: 20 experienced surgeons and 16 novice users.
Animal Testing: 24 animals (rats).

9. How Ground Truth for the Training Set Was Established

As noted above, there isn't a traditional "training set" for an AI/ML algorithm in this context. The "ground truth" for the various performance evaluations supporting the device's design and validation were established through:

Bench Testing: Established engineering standards and predefined mechanical/electrical parameters.
Cadaver/Animal Testing: Direct observation by expert surgeons, pathologist analysis (histology, micro-CT), and established medical tests (Acland milking test).
Simulated Use Testing: Objective measurements using a digital microscope, comparing robotic assistance to manual techniques.

These methods collectively served to validate the device's intended performance and safety, forming the "ground truth" for its development and regulatory acceptance.

Summary

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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

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.

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-mediatedPyrogenicity	ISO 10993-11:2017, ISO 10993-12:2021, and USP NF2022 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 ASTMF756-17	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
1. Content of Premarket Submissions for Device Software Functions, issued June 14, 2023
1. Off-the-Shelf Software Use in Medical Devices, issued August 11. 2023
1. IEC 62304 AMD 2015, Medical Device Software Software Life-Cycle Processes
1. 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.

TestDescription	Objective	Acceptance criteria	Results
Accuracy	Verify Symani Surgical Systemtranslational (XYZ) and orientational(RPY) accuracy.	(b)(4) for each translational axisRoll accuracy (b)(4)Pitch and Yaw accuracy (b)(4)	PASS
SystemResolution	Verify that the system is able toreplicate the user translational (XYZ)and orientational (RPY) motioncommand.	XXY axes (b)(4)RPY axes (b)(4)	PASS
Latency	Verify that the system is able toreplicate the user translational (XYZ)and orientational (RPY) motioncommand within the maximumallowed latency.	(b)(4)	PASS
Repeatability	Verify that the system is able totransmit the translational (XYZ)Master Controller movements toInstrument tip motions in areproducible manner.	(b)(4)	PASS
Scaling Testing	Verify that the system is able totranslate translational (XYZ) MasterController movements into a relativedisplacement of the Articulated Wristalong X, Y and Z axes with a settableconstant motion scaling down factor(7X, 10X, 12X, 20X).	(b)(4) scaling down factorswith a (b)(4) tolerance range	PASS
Hold Testing	Verify that the system is able to blockthe translational (XYZ) movementsof the Instrument while in HoldLimited Teleoperation	(b)(4)	PASS
WorkspaceTesting	Verify the translational movementsworkspace.	Each axis shall report a workspace valuebetween (b)(4)	PASS
	Verify the angular movementsworkspace.	(b)(4)	PASS
System Use-Life	Demonstrate that the SymaniSurgical System will maintain itsintegrity and operate properly over its10 year use-life.	No structural failure or malfunctions shallbe observed. No component shall berepaired or replaced.	PASS
Drop testing	Verify that multiple drops of theMaster Controller do not affect theSystem performances.	No impact on performances by MasterController drops.	PASS
Emergency StopTesting	Verify that the Instruments motionwill stop within a pre-defineddistance when the Stop button ispressed either on the GUI or on theConsole	Motors stops at(b)(4)	PASS
CuttingPerformance	Verify instruments performance incutting sutures	The Needle Holder Suture Cut instrumentshall allow to perform at least (b)(4)consecutive micro suture cuts.	PASS
StitchingPerformance	Verify instruments stitchingperformance	The Dilator instrument shall allow toperform at least (b) consecutive stitcheswith microsutures
		The Needle Holder and Needle SutureCut Instruments shall allow to perform atleast (b)(4) consecutive stitches withmicrosutures.
Grip Force		The Micro and Supermicro Needle HolderInstrument shall perform a minimumgripping force of (b)	PASS
	Verify the instruments grip force	The Needle Holder with Cutter Instrumentshall have gripping force reduced of max(b)(4) compared with Needle HolderInstrument.	PASS
Grip and Cutting	Verify that the Instruments will	Reliability of 95% and confidence level of	PASS
ReliabilityNeedleCompatibility	reliably grip and cut after aging.Verify that Needle Holder allows theuser to firmly grasp microsurgical	85% with grip force (b)(4)Micro Needle Holder shall firmly graspneedles with diameters between 150-70μm.	PASS
	needles.	Supermicro Needle Holder shall firmlygrasp needles with diameters below 100μm.	PASS
Knot Tying		The Micro Needle Holder and MicroNeedle Holder Suture Cut shall allow to tieknots with microsurgical suture in therange of 8-0 and 10-0.	PASS
	Verify that the Instruments are ableto handle and tie knots withmicrosurgical sutures	The Supermicro Needle Holder andSupermicro Needle Holder Suture Cutshall allow to tie knots with microsurgicalsuture in the range of 10-0 and 12-0	PASS
		The Micro Dilator instrument shall allowto tie knots with microsurgical suture inthe range of 8-0 and 10-0	PASS
		The Supermicro Dilator instrument shallallow to tie knots with microsurgicalsuture in the range of 10/0 and 12/0.	PASS
StructuralIntegrity Testing	Verify the Instruments shaft canwithstand worst-case load bendingconditions	The Instruments shaft shall not break.	PASS
StructuralIntegrity Testing	Verify the Instrument shaft andextremities can withstand multipleco-manipulation and collisionconditions	The Instruments shaft shall not break.	PASS
	Verify the Needle Holder Instrumentcan withstand repetitive grippingactions without functional orstructural failures	The Needle Holder shall withstandrepetitive gripping actions withoutfunctional (grip force(b)(4) or structuralfailures.	PASS
	Evaluate the Instrument's jawsresistance	Instruments tips shall withstand worst-case load conditions without breaking.	PASS
	Microscopecompatibility	The microscope's head and arm shall fitbetween Micromanipulators avoidingcollision with the Micromanipulators andInstruments
Verify 3rd party microscope'scompatibility with Symani		The working distance range shall beadequate to have an appropriate vision ofthe surgical site, whilst avoiding anycollision with Symani Instruments andMicromanipulators	PASS
		The user shall be able to setup the Symaniand the Vision System to reach the area tobe treated independently to the bodydistricts
		Each user involved in the surgery shallhave a clear vision of the operating fieldimage
		The user shall be able to manage themicroscope while seated at the surgicalconsole	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
1. 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.
1. 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.
1. Subjects who fit the criteria to perform surgery requiring reconstructions using free flaps. replantation, lymphatic reconstructions.
1. 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.
1. Any criteria that preclude prolonged anesthesia.
1. History of anaphylaxis or severe complicated allergy symptoms.
1. 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.
1. Evidence or history of autoimmune disease or compromised immune system.
1. Participation in another clinical trial within 4 weeks prior to participation in the study.
1. Subjects belonging to vulnerable populations or ineligible to participate for other reasons

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by the PI at a Clinical Center.

1. 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-operativeradiotherapy	n (%); N	70.8; 17/24	19.4; 3/31
Pre-operativechemotherapy	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 consumptionover 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-cardiacarteriopathy	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 ofAnesthesiologist Score(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(AES)	25	13	12	31	22	9
Full Analysis set(FAS)	24Excluded N=1(Manual suturesonly)	12Excluded N=1(Manualsutures only)	12	31	22	9
Free flapprocedures includedprimaryeffectivenessanalysis	17	7	10	21	13	8
Proceduresexcluded fromprimaryeffectivenessanalysis	N=7no follow-up at>=23 days N=7	N=5no follow-up at>=23 days N=5	N=2no follow-up at>=23 days N=2	10no follow-up at>=23 days N=8Buried flap: n=2	9no follow-up at>=23 days N=7Buried flap: n=2	N=1no follow-up at>=23 days N=1
Safety Set (SS)	Equivalent to FAS	Equivalent to FAS	Equivalent toFAS	Equivalent toFAS	Equivalent toFAS	Equivalent toFAS
Study completionstatus	Completed: 18Missing: 0Withdrawn: 7	Completed: 9Missing: 0Withdrawn: 4	Completed: 9Missing: 0Withdrawn: 3	Completed: 24Missing: 0Withdrawn: 7	Completed: 17Missing: 0Withdrawn: 5	Completed: 7Missing: 0Withdrawn: 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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VesselDiameter	Breast		Extremities
	Number ofanastomoses(N=24)	Percentage	Number ofanastomoses(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 ofanastomoses	Numberpatent	Patencyestimate	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 ofanastamoses	Anastomosisproceduretime (mins)	Number of sutures/anastamoses (n)	Average time persuture (mins)
Breast
Only roboticanastomoses	8	25.0(6.98)	7.6 (0.52)	3.28 (0.783)

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	Number ofanastamoses	Anastomosisproceduretime (mins)	Number of sutures/anastamoses (n)	Average time persuture (mins)
Hybrid: Bothrobotic andmanualanastomoses	4	32.5 (14.53)	Robotic: 8.0 (0.82)Manual: 1.8 (0.96)	Robotic: 3.27 (1.288)Manual: 4.00 (2.449)
Only manualanastomoses	6	18.3(4.41)	8.3 (0.52)	2.19 (0.499)
Extremities
Only roboticanastomoses*#	30	38.0(11.61)	8.5 (2.62)	4.28 (1.320)
Hybrid: Bothrobotic andmanualanastomoses	5	49.2 (12.50)	Robotic: 6.6 (3.36)Manual: 4.8 (3.11)	Robotic: 6.20 (3.109)Manual: 3.24 (1.714)
Only manualanastomoses	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%[0.1%, 16.7%]
Breast	0%[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

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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 AdverseEvents	Serious AdverseEvents	Device RelatedAdverse Events	Device RelatedSerious AdverseEvents
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 30days*	0.0% (0.0%,0.0%)	0.0% (0.0%,0.0%)
All-cause mortality rate through 30 days*	0.0% (0.0%,0.0%)	0.0% (0.0%,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	UpperExtremities	LowerExtremities
	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-operativeradiotherapy	n (%); N	45.7; 16/35	13.2; 5/38
Pre-operativechemotherapy	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 consumptionover 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	UpperExtremities	LowerExtremities
Extra-cardiacarteriopathy	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=70Excluded: n=3(Manual sutures only)	N=23Excluded: n=1(Manual sutures only)	N=27Excluded: n=1(Manual sutures only)	N=10Excluded: n=1(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 ofanastomoses(N=132)	Percentage
0.1-0.3 mm	28	21.2%
0.4-0.5 mm	53	40.4%
0.6-1.0 mm	49	37.1%
1.1-1.5 mm	2	1.5%

Lymphatic Surgery Results

Effectiveness Results:

Intra-operative patency is presented in Table 19. All vessels were patent by the second attempt. In these procedures if patency is not achieved on the first attempt the anastomosis is revised in the index procedure until patency is achieved. A limitation is that LVA patency was not accessed at 30 days. LVAs are different from the standard venous or arterial anastomoses created in free flap reconstruction, and LVA failure does not often occur immediately.

Site	Number ofanastomoses	Numberpatent	Patencyestimate	95% CI
Upper Extremity	60	58	96.7%	[88.5%, 99.6%]
Lower Extremity	70	66	94.3%	[86.0%, 98.4%]

Table 19: Intra-operative Anastomosis Patency on first attempt

The suturing time is shown in Table. The rate of intra-operative approach changes from robotic to manual is in Table 21. 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 20: Suturing time reported as mean ± standard deviation from the "all enrolled data set".
-------------------------------------------------------------------------------------------------	--	--

	Number ofanastamoses	Anastomosisprocedure time(mins)	Number ofsutures (n)	Average time persuture (mins)
Only roboticanastomoses*	90	32.2 (10.76)	6.7 (2.47)	5.39 (2.835)
Hybrid: Bothrobotic andmanualanastomoses	38	42.3 (17.64)	8.4 (2.59)	Robotic: 6.02(3.172)Manual: 4.37 (2.624)

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	Number ofanastamoses	Anastomosisprocedure time(mins)	Number ofsutures (n)	Average time persuture (mins)
Only manualanastomoses	42	25.7 (14.00)	6.6 (2.32)	4.05 (2.050)

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

Table 21: Intraoperative Approach Change for Free-Flap by Anatomical Site

Site	Number of changes	Percentage
Upper Extremity	4/60	6.7%
Lower Extremity	4/71	5.6%

Safety Results:

The adverse event rates are presented in Table 22. There were no device related adverse events. There was one serious adverse event occurring at upper extremity due to positive margin of the tumor resection site in the left breast, which was not related to the index procedure, nor the device.

Site	All Adverse Events	Serious Adverse Events	Device Related AdverseEvents
Upper Extremities	6.1%, 2/33	3.0%, 1/33	0%, 0/33
Lower Extremities	2.7%, 1/37	0%, 0/37	0%, 0/37

Table 22: Anatomical Site-Specific Adverse Event Rates for LVA

Estimates for the secondary analysis of other safety endpoints captured in the Symani study are shown in Table

Table 21: Other Safety Endpoints reports as mean percentage with the 95% confidence interval

Safety Endpoints	Upper Extremity	Lower Extremity
All-cause readmission rates through 30days*	0.00%(0.00%,0.00%)	0.00%(0.00%,0.00%)
All-cause mortality rate through 30 days*	0.00%(0.00%,0.00%)	0.00%(0.00%,0.00%)
30-day Reoperation rate*	0.00%(0.00%,0.00%)	0.00%(0.00%,0.00%)

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

Clinical Studies Conclusions

The Symani study achieved the objectives of performing and clinically evaluating safety and effectiveness in microvascular anastomosis in free-flap procedures and lymphovenous anastomosis in lymphatic surgery using the Symani Surgical System.

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Commercial Data and Literature

MMI has established a collaboration with the commercial sites to proactively collect procedurerelated information. The present data collection contains anecdotical information on 77 (115 anastomoses) free-flap and 22 (32 anastomoses) lymphatic procedures performed in 6 European centers. In the free-flap procedures 997 stiches were placed robotically and 160 stitches were placed manually. In the LVA procedures 181 stiches were placed robotically and 21 stitches were placed manually. Additionally, a qualitative survey of surgeons participating in a non-clinical study using artificial vessels showed higher satisfaction with Symani surgical system versus conventional microsurgery for an improvement in back and neck tenderness, and operative comfort [2]. The metrics for the scale were significantly worse, wors, equal, better, and significant better. Four experienced microsurgeons and three and users with no microsurgery experience, performed a total of 62 manual and robot-assisted anastomoses in this study. This non-clinical study also demonstrated that novice and experienced surgeons showed a fast-learning curve with significant improvements in anastomotic creation times by the 5th anastomosis. There was no significant difference between mean anastomosis time of the 5th robotic-assisted and manual anastomosis performed by novices. The 5th manual anastomosis was not evaluated for experienced surgeons.

LABELING

The Symani Surgical System provides Instructions for Use and Reprocessing Instructions complies with the labeling requirements under 21 CFR 801.109 for prescription devices.

Important components of the labeling include:

a detailed summary of in vivo performance testing conducted with the device, including . study population, results, adverse events, and comparisons to any comparator groups identified:
. a statement in the labeling that the safety and effectiveness of the device has not been evaluated for outcomes related to the treatment or prevention of cancer, including but not limited to risk reduction, overall survival, disease-free survival and local recurrence, unless FDA determines that it can be removed or modified based on clinical performance data submitted to FDA:
. identification of compatible devices:
. reprocessing instructions for reusable components;
. use life for reusable components:
. shelf life for any sterile components;
. a description of the device-specific use training program;
a statement that the device is only for distribution to facilities that implement and . maintain the device-specific use training program and ensure that users of the device have completed the device-specific use training program; and

The labeling also includes the cautions and warnings below:

. Caution: Long-term outcomes of lymphovenous anastomoses performed with the Symani System for the treatment of lymphedema have not been evaluated.

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. Warning: 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.
. Warning: Safety and effectiveness of Symani Surgical System has not been established for replantation of the fingers, toes, or limbs.
Warning: Safety and effectiveness of Symani Surgical System has not been established for . free-flap surgery of the head & neck and trunk.

See the labeling for a full list of contraindications, warnings, precautions, and limitations needed for safe use of the device.

DEVICE USE TRAINING PROGRAM

A training program was established to mitigate risk of use error that would result in patient injurv due to lack of familiarity with the complex systems and functions of Symani Surgical System. MMI designed a mandatory training program for surgeons and OR staff to ensure safe and efficient use of Symani in the clinical setting. The training is not intended as microsurgical training. Users must have adequate microsurgical qualifications to participate in the Symani training, which is focused on the safe use of the system during standard open microsurgical procedures.

The training program has been designed to progressively guide users (surgeons and OR staff) to independently using the Symani Surgical System.

Training consists of:

· Overview of the system's main components and their basic functions
Training on the systems' workflow (i.e., placement, set-up, teleoperating, . troubleshooting, etc.). The Surgeon and the OR Staff Workflow Trainings are conducted separately and are organized in different sections based on the activities to be performed by the different users.
. Surgeon skill training, which consist of practicing suturing using the devie and a vessel simulator.

Each phase of the training concludes with a completion that is based on confirming the successful execution of a series of phase's tasks, which permits progression to the next phase of training.

Upon successful completion of training, to ensure that the surgeon and the OR staff can independently use the Symani Surgical System in the clinical practice, the additional steps must be completed:

· In hospital dry run where the entire surgical team will perform a simulated procedure with the Symani Surgical System
For at least the first 5 clinical cases using the of the Symani Surgical System in the OR. . the surgeon will perform clinical cases with the assistance of a MMI Specialist.

This training program shall be updated at a minimum on a yearly basis (or more often if necessary) to ensure that the user population can safely and effectively use the Symani system

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(setup/use/shutdown, accurate control of instruments to perform the intended surgical procedures, troubleshooting and handling during unexpected events or emergencies, safe practices, etc.). The need for an update of the training program shall be evaluated based on circumstances such as: Symani software and hardware changes (e.g., changes on GUI), new instrument-models, feedback from MMI Specialists, user complaints, results of clinical data analysis, etc.

ANNUAL REPORTING

Annual Reporting serves to mitigate identified risks related to electrical fault, electromagnetic disturbances, mechanical fault, system malfunction resulting in injury to patient or delay of treatment and use error resulting in patient harm (e.g., flap failure, reoperation, necrosis, etc.). Software-controlled, electromechanical systems for open microsurgery are complex with many interlinking components and interfaces that will undergo technological changes and evolutions to enhance device safety and effectiveness. The regulatory criteria in 21 CFR 807.81(a)(3) state that a premarket notification must be submitted in the case of "a change or modification in the device that could significantly affect the safety or effectiveness of the device. e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process." However, even minor changes to a system component that do not rise to the level of requiring a premarket notification can unexpectedly magnify into clinically relevant device failure during use for this device. Therefore, it is critical that FDA understand even changes made to the device that would not require a 510(k) submission to understand their impact on the safety and effectiveness of the device.

The annual reports will contain a cumulative summary, by year, of complaints and adverse events since date of initial marketing authorization, as well as identification and rationale for changes made to the device, labeling, or device-specific use training program, which did not require submission of a premarket notification during the reporting period.

RISKS TO HEALTH

The table below identifies the risks to health that may be associated with use of an electromechanical system for open microsurgery.

Risks to Health	Mitigation Measures
Electrical fault, electromagneticDisturbances, mechanical fault, orsystem malfunction resulting intissue injury or prolongedprocedure time	In vivo performance testing
	Electrical safety testing
	Electromagnetic compatibility testing
	Non-clinical performance testing
	Software verification, validation, and hazard analysis
	Labeling
	Annual reporting
Adverse tissue reaction	Biocompatibility evaluation
	Pyrogenicity testing
Infection	Sterilization validation
	Reprocessing validation
	Biocompatibility evaluation
	Pyrogenicity testing
	Shelf-life validation

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Risks to Health	Mitigation Measures
Use error leading to patient harmor prolonged procedure time:	In vivo performance testingLabeling
Tissue injury Reoperation Thrombosis Flap failure Necrosis Hematoma	In vivo performance testingPostmarket surveillanceTrainingHuman factors testingLabelingAnnual reporting

SPECIAL CONTROLS

In combination with the general controls of the FD&C Act, the electromechanical system for open microsurgery is subject to the following special controls:

(1) Data obtained from premarket in vivo performance validation testing and postmarket data acquired under anticipated conditions of use must demonstrate that the device performs as intended in the intended patient population and anatomical location, unless FDA determines based on the totality of the information provided for premarket review that data from postmarket surveillance is not required. Objective performance measures (e.g., patency and rate of device related adverse events and their severity, cause, and outcomes) for the device and a clinically justified comparator must be reported with relevant descriptive or developmental performance measures
(2) The device manufacturer must develop. and update as necessary, a device-specific use training program that ensures proper device setup/use/shutdown, accurate control of instruments to perform the intended surgical techniques, troubleshooting and handling during unexpected events or emergencies, and safe practices to mitigate use error.
(3) The device manufacturer may only distribute the device to facilities that implement and maintain the device-specific use training program and ensure that users of the device have completed the device-specific use training program.
(4) Labeling must include:
- A detailed summary of in vivo performance testing conducted with the device. (i) including study population, results, adverse events, and comparisons to any comparator groups identified:
- (ii) A statement in the labeling that the safety and effectiveness of the device has not been evaluated for outcomes related to the treatment or prevention of cancer, including but not limited to risk reduction, overall survival, disease-free survival and local recurrence, unless FDA determines that it can be removed or modified based on clinical performance data submitted to FDA;
- Identification of compatible devices; (iii)

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(iv) Reprocessing instructions for reusable components;
Use life for reusable components; (v)
(vi) Shelf life for any sterile components;
(vii) A description of the device-specific use training program;
(viii) A statement that the device is only for distribution to facilities that implement and maintain the device-specific use training program and ensure that users of the device have completed the device-specific use training program; and
(ix) A detailed summary of the postmarket surveillance data collected under paragraph (1) of this section and any necessary modifications to the labeling to accurately reflect outcomes based upon the postmarket data collected under paragraph (1) of this section.
Human factors validation testing must be performed and must demonstrate that the (5) device/user interfaces of the system support safe use in all use environments.
(6) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use and must include:
- Device motion accuracy and repeatability; (i)
- System testing: (ii)
- (iii) Instrument reliability;
- User-device interface performance: (iv)
- Workspace access testing; and (v)
- Performance testing with compatible devices. (vi)

Software verification, validation, and hazard analysis must be performed.

(8) Electromagnetic compatibility and electrical, thermal, and mechanical safety testing must be performed.
(9) Performance data must demonstrate the sterility of all patient-contacting device components.
(10) Performance data must support the shelf life of the device components provided sterile by demonstrating continued sterility and package integrity over the labeled shelf life.
(11) Performance data must validate the reprocessing instructions for the reusable components of the device.
(12) Performance data must demonstrate that all patient-contacting components of the device are biocompatible.
(13) Performance data must demonstrate that all patient-contacting components of the device are non-pyrogenic.
(14) The device manufacturer must submit a report to the FDA annually on the anniversary of initial marketing authorization for the device, until such time as FDA may terminate

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such reporting, which comprises the following information:

Cumulative summary, by year, of complaints and adverse events since date of (i) initial marketing authorization; and
(ii) Identification and rationale for changes made to the device, labeling, or devicespecific use training program, which did not require submission of a premarket notification during the reporting period.

BENEFIT/RISK DETERMINATION

Risks

The risks of the device are based on data collected in the non-clinical and in vivo studies described above.

General risks of the Symani Surgical System include:

1. Electromagnetic disturbances, electrical fault, mechanical fault, or system malfunction resulting in patient injury or a delay of treatment or patient harm. There was one device related adverse event resulting in tissue injury. The feature that contributed to this injury was removed from the device. There were device malfunctions that resulted in the surgeon converting to manual anastomoses. However, none of these events resulted in tissue injury with a minimal delay in treatment due to the device's fluid integration into and out of the workflow. The risks have been mitigated through bench, thermal safety, mechanical safety, electrical safety, electromagnetic compatibility, software testing, and labeling. These risks will also be mitigated through annual reporting.
1. Use error resulting in patient harm such as tissue injury, thrombus formation, or reoperation is a risk. There was no thrombosis contributing to anastomosis failure. There was one reoperation to revise the anastomosis in the extremities (1/31; 3.23%) due to failure after the index free-flap procedure, however this rate is lower than literature [3]. This risk has been mitigated through human factors validation testing, in vivo testing, and labeling. This risk will also be mitigated through annual reporting.
1. The device has shown to prolong the operation, which places the patient at higher risks to anesthetic treatment and medications. This risk has been mitigated through in vivo testing. These risks will also be mitigated through annual reporting.

The patient population (i.e., sample size, demographic, comorbidities) was a limitation with the in vivo study. The demographics and comorbid conditions between the in vivo study and the United States population are different. A postmarket study will be conducted evaluating safety (e.g., anastomosis-specific reoperation rate through 3 days) in a population representative of the general United States population in free-flap procedures of the breast and extermities.

Benefits

The probable benefits of the device are also based on the non-clinical and in vivo studies as described above.

Probable benefits of the Symani Surgical System include:

1. The device's technology (i.e., motion scaling, tremor reduction) makes it an effective

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surgical tool for the creation of micro-surgical vessel anastomoses. In the animal study the robotic intra-operative patency rate (100%) was similar to manual (100%). In the 28-day post-operative period, the robotic patency rate (100%) was greater than manual (93.8%). The vascular anastomosis patency rate at first attempt was 100% for the breast and 90.9% for the extremities in free-flap procedures. The lymphovenous anastomosis patency rate at first attempt was 96.7% for the upper extremities and 94.3% for the lower extremities in lymphatic surgery. All lymphovenous anastomoses were patent by the second attempt.

1. The device improves the performance and accuracy of microvascular suturing. Both experienced microsurgeons and users with no microsurgery experience had improved needle angulation entrance accuracy during suturing. The cohort of users with no microsurgery experience demonstrated a statistically significant improvement compared to suturing manually in pre-clinical data.
1. The device integrates into the workflow for microvascular anastomotic creation, with features that support patient safety and improve surgeon comfort and musculoskeletal pain. The use of the device takes seconds to minutes to move in-and-out of the operative field. supporting fluid integration into the normal surgical workflow. The hand controllers are used and held in a similar fashion to manual instruments, which allows for efficient transference between operative approaches. Also, the surgeon remains scrubbed by the bedside while utilizing their preferred compatible microscope, which supports patient safety and is evidenced similar 3-day reoperation rates compared to the literature comparator [3]. With the device's integration into workflow, the user can elect to place the stitches entirely robotically or with a combined robotic and manual hybrid-type application, depending on anatomic considerations and/or user preference. A qualitative survey of surgeons participating in a non-clinical study using artificial vessels showed greater satisfaction with the Symani surgical system versus conventional microsurgery, specifically, an improvement in back and neck tenderness and operative comfort [2]. This study also demonstrated that experienced mricosurgeons and users with no microsurgery experience showed a fast-learning curve with significant improvements in anastomotic creation times by the 5th anastomosis [2] ..

The in vivo studies did not evaluate long-term effectivness associated with creating a lymphovenous anastomosis in lymphatic procedures using the Symani Surgical System. Due to the risks being low for lymphatic surgery this will be evaluated in a postmarket study in a population representative of the general United States population. Additionally, while the nonclinical data demonstrated a fast-learning curve with Symani, the clincal data demonstrated that use of this device increased the suturing time compared to manual suturing in clinical use. This may put patients at a higher risk to anesthetic treatment and medications. To further mitigate this risk a postmarket study will also be conducted in all the procedures (i.e., free-flap procedures of breast and extremities and lymphatic procedures of the extremities) to determine the learning curve for novice and experienced surgeons evaluating robotic suturing proficiency with increased experience using the Symani Surgical System.

Patient Perspectives

This submission did not include specific information on patient perspectives for this device.

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Benefit/Risk Conclusion

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

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 surgeon. 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

The probable benefits outweigh the probable risks for the Symani Surgical System. The device provides benefits, and the risks can be mitigated by the use of special controls.

Conclusion

The De Novo request for the Symani Surgical System is granted and the device is classified under the following:

Product Code: SAO Device Type: Electromechanical system for open microsurgery Regulation: 21 CFR 878.4963 Class: II

REFERENCES

1. Ballestin A et al. New Robotic System with Wristed Microinstruments Allows Precise Reconstructive Microsurgery: Preclinical Study. Ann Surg Oncol. 2022; 29(12):7859-7867. doi: 10.1245/s10434-022-12033-x.
1. Wessel K.J. et al., Combined Application of a Novel Robotic System and Exoscope for Microsurgical Anastomoses: Preclinical Performance, Journal of Reconstructive Microsurgery Open. Nov 2023.
1. Arakelyan S. Aydogan E. Spindler N, Langer S, Bota O. A retrospective evaluation of 182 free flaps in extremity reconstruction and review of the literature. GMS Interdiscip Plast Reconstr Surg DGPW. 2022 Jan 14;11:Doc01. doi: 10.3205/iprs000162. PMID: 35111561; PMCID: PMC8779818.

Regulation Number and Section

N/A