K Number

Device Name

MagDI System

Manufacturer

GT Metabolic Solutions, Inc.

Date Cleared

2024-07-02

(98 days)

Product Code

SAH

Regulation Number

878.4816

Intended Use

The GT Metabolic MagDI System is intended for use in the creation of side-to-side duodeno-ileal anastomoses in minimally invasive and laparoscopic surgery. Once wound strength is sufficient to maintain the anastomosis, the device is passed from the body. The effects of this device on weight loss were not studied. The GT Metabolic MagDI System is intended for use in adult patients > 21 vears.

Device Description

The MagDI System is comprised of two (2) GT Metabolic DI Magnet ("Magnet") devices delivered sequentially with a minimally invasive GT Metabolic Delivery System ("Delivery System"). Class I magnetic surgical instruments (GT Metabolic Laparoscopic Positioning Device: FDA Listing #D512834) are used to position the Magnets to the target anastomosis locations in the duodenum and ileum and connect the two Magnets. The device provides a method for the creation of a round (oval/circular) compression anastomosis. After a period of approximately 7-21 days, a compression-induced necrosis of the tissue between the Magnets occurs and the whole device, together with the necrosed tissue that was compressed by the Magnets, detaches, and is naturally expelled with the stool. The MagDI System components (Magnets and Delivery System), as shown in Figures 1 and 2 below, are provided sterile and are for single use.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

D512834

Reference Devices

D512834

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a mechanical device that uses magnets to create an anastomosis. There is no mention of AI, ML, image processing, or any data-driven decision-making components.

Therapeutic

Yes

The device aids in creating duodeno-ileal anastomoses, a surgical procedure to address a medical condition, by facilitating tissue necrosis and subsequent expulsion. This constitutes a therapeutic effect by enabling a physiological repair mechanism.

Diagnostic

The device is intended for the creation of side-to-side duodeno-ileal anastomoses in surgery, providing a method for forming a compression anastomosis and then being expelled from the body. Its purpose is therapeutic/surgical, not to diagnose a condition.

SaMD (Software as a Medical Device)

The device description clearly states the system is comprised of physical components: two GT Metabolic DI Magnets and a GT Metabolic Delivery System. It also mentions the use of Class I magnetic surgical instruments for positioning. This indicates a hardware-based medical device, not a software-only one.

IVD (In Vitro Diagnostic)

No, this device is not an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use is for the creation of surgical anastomoses (connections) within the body, specifically in the duodeno-ileal region. This is a surgical procedure performed in vivo (within a living organism).
Device Description: The device is a system of magnets and a delivery system used to physically create a connection between two parts of the intestine. It works by applying compression to tissue within the body.
Mechanism of Action: The device creates a compression-induced necrosis of tissue in vivo, leading to the formation of an anastomosis and subsequent expulsion from the body.
Lack of Diagnostic Function: The device does not perform any tests on samples taken from the body (like blood, urine, or tissue samples) to diagnose a condition, monitor a disease, or screen for a disease.

IVD devices are used to examine specimens in vitro (outside of the body) to provide information for diagnostic purposes. This device is a surgical tool used in vivo to perform a therapeutic procedure.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The GT Metabolic MagDI System is intended for use in adult patients > 21 years.

Product codes

SAH

Device Description

After a period of approximately 7-21 days, a compression-induced necrosis of the tissue between the Magnets occurs and the whole device, together with the necrosed tissue that was compressed by the Magnets, detaches, and is naturally expelled with the stool.

The MagDI System components (Magnets and Delivery System) are provided sterile and are for single use.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

duodeno-ileal, gastrointestinal tract, small bowel (duodenum, jejunum, ileum)

Indicated Patient Age Range

adult patients > 21 years

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Performance Testing - Animal and/or Cadaver:
Development and verification porcine studies (n=9) over 6 weeks were conducted for the MagDI System with a comparison to sutured enterotomies as a proxy for the conventional hand-sutured anastomotic technique.

Porcine Developmental Study:

Study Type and Objective: Porcine (n=5) developmental study. To evaluate the feasibility and safety of the side-to-side anastomosis procedure.
Follow-up Duration: 6 weeks (41-42 days)
Procedure: Side-to-side magnetic duodeno-ileostomy was performed with both magnetic anastomosis delivered endoscopically (by gastroscope) or by an intestinal incision via laparotomy or laparoscopy.

Porcine Verification Study:

Study Type and Objective: Porcine (n=4) verification study. Evaluation of the feasibility and efficacy of a magnetic anastomosis device delivered surgically and endoscopically to create a side-to-side anastomosis in a swine model over 6 weeks.
Follow-up Duration: 6 weeks (41-42 days)
Procedure: Side-to-side magnetic duodeno-ileostomy was performed with both magnetic anastomosis devices delivered endoscopically (by gastroscope) or by an intestinal incision via laparotomy or laparoscopy. The Magnets were positioned and moved to the final anastomosis site using a Laparoscopic Positioning Device.

Clinical Study:

Study Title: Creation of Side-to-Side Compression Anastomosis Using the GT Metabolic Solutions Magnetic Anastomosis System (MAGNET System) to Achieve Duodeno-Ileostomy Diversion in Adults with Obesity and with or without Type 2 Diabetes Mellitus: The MAGNET Study
Protocol Number / NCT Number: GTM-001 / NCT05322122
Study Design: Operationally seamless, 2-stage, open-label, multicenter study enrolling up to 50 subjects at 5 study centers across Canada and Europe. Stage 1 first-in-human (FIH) and proof-of-concept with 5 subjects; and Stage 2 feasibility with 45 subjects. All subjects in Stage 1 and 2 are followed for 12 months.
Study Population: Adults (18 to 65 years of age, inclusive) with obesity (BMI 30-50) who meet one of the following criteria: (1) have type 2 diabetes mellitus (T2DM) or experienced weight regain following previous sleeve gastrectomy; (2) have T2DM without previous sleeve gastrectomy; or (3) are candidates for a laparoscopic single anastomosis duodenal-ileal bypass with sleeve (SADI-S) procedure and have BMI ≥ 40.
Primary and Safety Endpoints: Primary: Feasibility/performance - Placement of the MAGNET System (≥ 90% alignment of magnets); and Passage of magnets without surgical re-intervention; and Creation of a patent anastomosis, confirmed radiologically. Safety: Incidence of treatment emergent AEs.
Sample Size: Forty-nine (49) subjects were treated.
Data Source: Four (4) centers in Belgium, Canada, Republic of Georgia, and Spain.
Enrollment Criteria:
- Inclusion Criteria:
  1. 18-65 years of age, inclusive, at the time of informed consent
  2. BMI 30-50, inclusive with either:
    a. Previous-sleeve gastrectomy (> 12 months) with either T2DM (defined as HbAlc > 6.5%) or weight regain; or
    b. T2DM without previous gastrectomy; or
    c. Undergoing laparoscopic single anastomosis duodenal-ileal bypass with sleeve (SADIS) where duodeno-ileostomy is performed side to side with the MAGNET System and BMI ≥ 40
  3. Agrees to refrain from any type of additional bariatric or reconstructive surgery that would affect body weight for 1 year
  4. If a child-bearing female, subject must commit to not becoming pregnant and agree to use contraception for 1 year
  5. Willing and able to comply with protocol requirements
- Exclusion Criteria:
  1. Type 1 diabetes
  2. Use of injectable insulin
  3. Uncontrolled T2DM
  4. Uncontrolled hypertension, dyslipidemia or sleep apnea
  5. Prior intestinal, colonic or duodenal surgery, other than bariatric
  6. Prior surgery, trauma, prostheses, disease or genetic expression which prevent or contraindicate the procedure, including scarring and abnormal anatomy.
  7. Refractory gastro-esophageal reflux disease (GERD)
  8. Barrett's disease
  9. Helicobacter pylori positive and/or active ulcer disease
  10. Large hiatal hernia
  11. Inflammatory bowel or colonic diverticulitis disease
  12. Any anomaly precluding orogastric access by gastroscope and catheters, and manipulation techniques.
  13. Implantable pacemaker or defibrillator
  14. Psychiatric disorder, except well-controlled depression with medication for > 6 mo, or history of substance abuse
  15. Woman who is either pregnant or breast feeding
  16. Woman of childbearing potential who does not agree to use an effective method of contraception.
  17. Any comorbidity or current status of subject's physiological fitness that in the surgeon's or anesthesiologist's opinion represents safety concerns that make the subject medically unfit for the procedure. This includes any conditions for which endoscopic or laparoscopic surgery would be contraindicated, and any significant congenital or acquired anomalies of the GI tract at or distal to the placement of the magnets.
  18. Unhealed ulcers, bleeding lesions, turnor or any other lesion at target magnet deployment site
  19. Expected need for MR imaging within the first 2 months after the procedure
  20. Any anomaly preventing/contraindicating laparoscopic access and general laparoscopic procedures
  21. Had surgical or interventional procedure within 30 days prior to procedure
  22. Any scheduled surgical or interventional procedure planned within 30 days postprocedure
  23. Any stroke/TIA within 6 months prior to consent
  24. Requires chronic anticoagulation therapy (except aspirin)
  25. Active infections requiring antibiotic therapy, unless resolved before undergoing the study procedure
  26. Unable to comply with the follow-up schedule and assessments
  27. Recent tobacco or nicotine product cessation within

Regulation Number and Section

N/A

Summary

DE NOVO CLASSIFICATION REQUEST FOR MAGDITM SYSTEM

REGULATORY INFORMATION

FDA identifies this generic type of device as:

Magnetic compression anastomosis system. A magnetic compression anastomosis system is a surgical device used for the creation of anastomoses in minimally invasive and laparoscopic surgery in the gastrointestinal tract. The system is comprised of magnet devices and may involve a delivery system. Compression and necrosis of tissue between magnet devices is created by polar attraction of the magnet devices with healing of tissue around the devices. Once the anastomosis is formed, the magnet devices are expelled naturally. This classification does not include devices intended for weight loss or metabolic disease treatment.

NEW REGULATION NUMBER: 21 CFR 878.4816

CLASSIFICATION: Class II

PRODUCT CODE: SAH

BACKGROUND

DEVICE NAME: MagDI System

SUBMISSION NUMBER: DEN240013

DATE DE NOVO RECEIVED: March 26, 2024

SPONSOR INFORMATION:

GT Metabolic Solutions, Inc. 5450 Quam Ave NE. Suite 100 St. Michael, Minnesota 55376

INDICATIONS FOR USE

The MagDI System is indicated as follows:

The GT Metabolic MagDI System is intended for use in adult patients > 21 vears.

LIMITATIONS

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

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

DEVICE DESCRIPTION

The MagDI System components (Magnets and Delivery System), as shown in Figures 1 and 2 below, are provided sterile and are for single use.

Image /page/1/Picture/7 description: The image contains two separate images of a gray container with a green handle. The first image shows the container from a distance, and the second image shows a close up of the handle. The container is rectangular with rounded edges. The handle is attached to the container with a small metal ring.

Figure 1: GT Metabolic DI Magnet Assembly (left), Attachment [Tube Assembly] (right)

Image /page/1/Picture/9 description: The image shows a medical device on a white surface. The device has a long, thin, gray cable that is connected to a small, silver, oval-shaped sensor. The other end of the cable is connected to a white, plastic handle with a trigger mechanism and a metal ring. The device appears to be a type of medical sensor or probe used for diagnostic or therapeutic purposes.

Figure 2: Delivery System with Magnet Attached

SUMMARY OF NONCLINICAL/BENCH STUDIES

PERFORMANCE TESTING - BENCH

The MagDI System underwent design verification testing (DVT) to ensure package integrity and device performance as described Table 1. The Magnets and Delivery System passed all testing demonstrating the device performs as expected under anticipated conditions of use. All testing occurred on units that were pre-conditioned per the requirements of recommended international standards to substantiate distribution and a prescribed shelf life.

Test	Purpose	Methods/Standard	Acceptance Criteria
Visual Inspection,
Product Packages
(Magnet/Delivery
System)	Visual inspection for
gross physical defects.	Visual inspection for gross
physical defects.	No obvious damage. All
seals must be intact.
Labels must be readable
by human eye and
barcode scanner.	Pass
Visual Inspection,
Package / Device
(Magnet/Delivery
System)	Visual inspection for
gross damage.	Peel pouch, verify product
retention within
packaging, inspect product
for gross visual damage.	The pouch must peel
consistently. Product
removes from pouch
easily. No damage or
defects to the device.	Pass
Device Inspection	Inspection for damage to
the device.	Visual inspection for
damage and anomalies.	No damage to the device.
Magnet Suture intact.	Pass
Magnet Separation
Force	Demonstrate product
integrity following
conditioning.	Measure separation force.	(b)(4)	Pass
Assembly Pull Test
(Magnet/Delivery
System)	Demonstrate product
integrity following
conditioning.	Tensile loading and
unloading force cycle
without the Magnets
disengaging or
damage/failure of any
joints of the entire system.	(b)(4)	Pass
Simulated Use
(Magnet/Delivery
System)	Demonstrate product
integrity following
conditioning.	The Delivery System
loaded with the Magnet
must be navigated through
a tortuous path.	Reach target, deploy
magnet, and withdrawal.
Slide deployment force (b)
(b)(4)	Pass
Suture Loop Pull Test
(Magnet)	Demonstrate product
integrity following
conditioning.	Force test assembly at a
fixed rate.	(b)(4)	Pass
Assembly Torque Test
(Magnet)	Demonstrate product
integrity following
conditioning.	Torque test assembly to
fixed position.	(b)(4)	Pass
Package Test, Bubble
Leak (Magnet/Delivery
System)	Demonstrate product and
package integrity
following conditioning.	ASTM F2096	Pouches must not show
evidence of seal or
channel leakage.	Pass
Package Test, Peel
Strength
(Magnet/Delivery
System)	Demonstrate product and
package integrity
following conditioning.	ASTM F88	Peel strength must be (b)(4)
(b)(4)	Pass

Table 1: Summary of Nonclinical/Bench Studies:

Test	Purpose	Methods / Standard
Delivery System Pull
Pin Test	Demonstrate product
integrity following
conditioning.	Tensile and compression
test Delivery System Pin	(b)(4)	Pass
Crimped Weld Pull
Test (Delivery System)	Demonstrate product
integrity following
conditioning.	Tensile test mechanical
connection.	(b)(4)	Pass

BIOCOMPATIBILITY/MATERIALS

Biocompatibility for the MagDI System was assessed according to FDA's Biocompatibility Guidance, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" Guidance for Industry and Food and Drug Administration Staff. All patient-contacting components of the MagDI System passed per ISO 10993-1.

Table 2: Magnet Materials, Type and Duration of Contact
---------------------------------------------------------	--

| Material | Type and Duration of Contact
(ISO 10993-1) |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|
| • Titanium (Ti-6Al-4V ELI, Grade 23) alloy
• Parylene C-coated neodymium-iron-boron
(NdFeB) magnet
• 304 stainless steel
• 316 stainless steel
• Nitinol wire
• Tevdek® (PFTE-coated polyester) braided
suture
• Loctite® 4011 Instant Adhesive
(cyanoacrylate) | Type of Contact:
Surface
Mucosal membrane
Duration of Contact:
Long-term (> 30 days) |

Table 3: Biocompatibility Testing Summary for Magnets

Test Performed	Test Method	Results
Cytotoxicity MEM Elution	ISO 10993-5: MEM Elution Study used to
evaluate device extracts for cytotoxicity risks.	Pass - non-cytotoxic
Skin Sensitization	ISO 10993-10: Guinea Pig Maximization
Sensitization Test used to evaluate device
extracts for dermal sensitization risks	Pass - not a sensitizer
Intracutaneous Irritation	ISO 10993-23: Intracutaneous Irritation Test
used to evaluate device extracts for irritation
risks	Pass - non-irritant
Acute Systemic Toxicity	ISO 10993-11: Acute systemic toxicity study
used to evaluate device extracts for systemic
toxicity risks	Pass - no signs of systemic
toxicity
Material-Mediated
Pyrogenicity	ISO 10993-11: Rabbit pyrogen test used to
evaluate device extracts for pyrogenicity risks.	Pass - non-pyrogenic
Subacute / Subchronic Toxicity	ISO 10993-11: Biological Evaluation of Medical
Devices - Part 11: Tests for Systemic Toxicity	Pass - no signs of
subchronic systemic toxicity
Genotoxicity (Ames Assay/
Mouse Lymphoma Assay)	ISO 10993-3: Biological Evaluation of Medical
Devices Part 3: Tests for Genotoxicity,
Carcinogenicity, and Reproductive Toxicity.	Pass - non-mutagenic

Test Performed	Test Method	Results
Implantation	ISO 10993-6: Biological Evaluation of Medical
Devices - Part 6: Tests For Local Effects After
Implantation	Pass - See Performance
Testing - Animal
Chronic Toxicity	ISO 10993-11: Biological Evaluation of Medical
Devices - Part 11: Tests for Systemic Toxicity	Pass - See Performance
Testing - Animal

Table 4: Delivery System Materials, Type and Duration of Contact

| Material | Patient Contact and Duration
(ISO 10993-1) |
|--------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------|
| • Nitinol
• 304V stainless steel
• Hytrel® (DuPont polymer) 55D / 82D | Type of Contact:
Surface
Mucosal membrane

Duration of Contact:
Limited (≤ 24 hrs.) |
| • 18-8 stainless steel
• 316 stainless steel
• PEEKTM
• 304 stainless steel | Type of Contact:
Non-patient contacting |

Table 5: Biocompatibility Testing Summary for Delivery System

Test Performed	Test Method	Results
Cytotoxicity MEM Elution	ISO 10993-5: MEM Elution Study used to
evaluate device extracts for cytotoxicity risks.	Pass - non-cytotoxic
Skin Sensitization	ISO 10993-10: Guinea Pig Maximization
Sensitization Test used to evaluate device extracts
for dermal sensitization risks	Pass - not a sensitizer
Intracutaneous Irritation	ISO 10993-23: Intracutaneous Irritation Test used
to evaluate device extracts for irritation risks	Pass - non-irritant

SHELF LIFE/STERILITY

Shelf-life testing comprised of aging the MagDI System and then performing the design verification testing (see Table 1: Performance Testing - Bench).

The MagDI System (Magnet and Delivery System) was fully validated for sterility via gamma irradiation per ISO 11137-1 - Sterilization of Health Care Products - Radiation. All package integrity testing related to sterility was tested as part of the design verification testing (see Table 1: Performance Testing - Bench) All testing occurred on units that were pre-conditioned per the requirements of recommended international standards to substantiate distribution and a prescribed shelf life.

ELECTROMAGNETIC CAPABILITY & ELECTROMAGNETIC SAFETY

The MagDI System is not a medical electrical device, so the IEC 60601-1 technical standard and associated electrical, mechanical, and thermal safety testing does not apply.

The MagDI System utilizes magnetic technology to produce mechanical compression for the anastomosis. Static magnetic field strength testing was conducted on the Magnets and evaluated against the thresholds set by the National Institute of Standards and Technology (NIST') and the International Commission on Non-Ionizing Radiation Protection (ICNIRP2) for occupational exposure, the general public, and medical device wearers. The testing demonstrated that the static magnetic field strength of two connected Magnets rapidly decays to well below 5 gauss at a distance of 1.5 inches. The exposure for intended users remains significantly below the identified thresholds and appropriate mitigation for patients has been incorporated in the instructions for use (IFU), including contraindication for use in patients with implantable devices or other metal and MR unsafe labeling.

References:

1. National Institute of Standards and Technology (NIST), U.S. Department of Commerce. Magnetic Field Safety. NIST S 7101.53. Document Approval Date: 01/05/2021. Downloaded 04MAR2024, https://www.nist.gov/oshe/safety-programs/magnetic-fieldsafety-program.
1. International Commission on Non-Ionizing Radiation Protection (ICNIRP). ICNIRP Guidelines on Limits of Exposure to Static Magnetic Fields. Published in Health Physics; 2009. 96(4):504-514. http://www.icnirp.org/cms/upload/publications/ICNIRPstatgdl.pdf.

MAGNETIC RESONANCE (MR) COMPATIBILITY

The MagDI System is MR unsafe.

SOFTWARE

The MagDI System does not contain software.

PERFORMANCE TESTING - ANIMAL AND/OR CADAVER

Development and verification porcine studies (n=9: see Tables 8 and 9) over 6 weeks were conducted for the MagDI System with a comparison to sutured enterotomies as a proxy for the conventional hand-sutured anastomotic technique.

Table 8: Porcine Developmental study

Evaluation of a Magnetic Anastomosis Devices in a Swine Model over 6 Weeks

Study Type and Objective:

Porcine (n=5) developmental study.

To evaluate the feasibility and safety of the side-to-side anastomosis procedure. The hybrid pig small bowel has a shorter duodenum and ileum compared to jejunum than in the human. Thus, this animal study procedure created a duodeno-jejunal anastomosis that represents the duodeno-ileal anastomosis procedure in the clinical study.

Follow-up Duration:

6 weeks (41-42 days)

Procedure:

· Side-to-side magnetic duodeno-ileostomy was performed with both magnetic anastomosis delivered endoscopically (by gastroscope) or by an intestinal incision via laparotomy or laparoscopy.

Safety Outcomes:

· One (1) out of the five (5) animals had an internal hernia that resulted in death on Day 4. The death was

determined to be procedure related and was diagnosed as hypovolemic shock due to entrapment of a large section of the jejunum in a mesenteric defect (internal hernia) and not related to the device.

· The device was released into the anastomotic site at a mean of 12.5 days (range 10-14 days) with peri-anal expulsion occurring at a mean of 23.7 days (range 13-34 days) (n=4 animals).
· Animals continued an expected growth (weight gain) path.
· Patent anastomoses were observed in the animals (n=4).

Conclusions:

· The MagDI System successfully induced a duodeno-ileal anastomosis in pigs when placed surgically and endoscopically. They were well tolerated clinically and were associated with a good healing response when evaluated microscopically, characterized by low levels of inflammation and tissue disruption and absence of adhesions at the placement sites at 6 weeks post-operatively.
· Although one (1) animal died due to an internal hernia, the death was determined to not be related to the MagDI System, but due to the surgical procedure. Closure of mesenteric defects in swine is impractical, as the mesentery is paper thin and sustains hematoma when attempting closure with sutures, a task that can normally be performed successfully in humans with much less difficulty to reduce the risk of mesenteric internal hernias. 1.2

Table 9: Porcine Verification Study

Evaluation of a Magnetic Anastomosis Devices in a Swine Model over 6 Weeks

Study Type and Objective:

Porcine (n=4) verification study.

Evaluation of the feasibility and efficacy of a magnetic anastomosis device delivered surgically and endoscopically to create a side-to-side anastomosis in a swine model over 6 weeks. The hybrid pig small bowel has a shorter duodenum and ileum compared to jejunum than in the human. Thus, this animal study procedure created a duodeno-jejunal anastomosis that represents the duodeno-ileal anastomosis procedure in the clinical study.

Follow-up Duration:

6 weeks (41-42 days)

Procedure:

· Side-to-side magnetic duodeno-ileostomy was performed with both magnetic anastomosis devices delivered endoscopically (by gastroscope) or by an intestinal incision via laparotomy or laparoscopy. The magnets were positioned and moved to the final anastomosis site using a Laparoscopic Positioning Device.

Safety Outcomes:

· The device was released into the anastomotic site at a mean of 16 days (range 12-22 days) with peri-anal expulsion occurring at a mean of 24.5 days (range 17-33 days).
· All animals continued an expected growth (weight gain) path.
· Patent anastomoses were observed in all the animals.
· Minor observations of abdominal adhesions were made in 2 of the 4 animals. This observation is consistent with humans who have had abdominal surgery.
· The anastomoses created by the magnets were observed to be fully neovascularized and free of surgical injury. granuloma, and scarring. By comparison, the jejunal enterotomy (performed to compare sutured tissue to the magnet anastomosis tissue) exhibited normal surgical injury characterized by scarring. These observations were replicated histologically, where the remodeled tissue at the anastomosis more closely resembles minimally disturbed tissue.

Conclusions:

Use of a magnetic compression anastomosis system to induce a duodeno-ileal anastomosis was associated with a good healing response characterized by low levels of inflammation and minimal tissue reaction as well as good vascularization at the site of device placement at 6 weeks post-operatively. These observations are in agreement with prior studies that conclude the establishment of anastomoses by compression is as effective and safe as those established by sutures or staples.3 The company's surgical advisors recommend closure of mesenteric defect(s) to decrease the likelihood of an internal hernia with associated intestion. Occurrence of mesenteric defects is a well-known complication in laparoscopic bariatric surgery and can be addressed with standard techniques in humans.

The subject device was successfully placed (with appropriate alignment of two Magnets) and created patent anastomoses in all (100%, 9/9) of the duodeno-jejunal cases in the porcine studies. This testing location is representative of the small bowel (comprised of duodenum, jejunum, and ileum) as the duodenum is the most challenging portion of the small bowel given its proximity to other organs (e.g., pancreas, gallbladder) and the jejunum and ileum are similar in structure and function.

Magnet devices were expelled per anus naturally as a connected set (Magnets connected together) without the need for surgical or other re-intervention to retrieve the devices. Visual inspection of the Magnets revealed indications of usage, such as minor scratches and

discoloration of the metal. All anastomoses were fully formed with healthy anastomotic tissue as documented by necropsy and histology. There were no cases of device migration as monitored by x-rays and no adverse events reported related to migration (e.g., bleeding, lesions, fistula) in the studies. This animal model, with direct comparison to the conventional suturing anastomotic technique, evaluates safe and effective use of the device to produce patent side-to-side anastomoses in the small bowel.

These animal study results are published in the literature:

Gagner M. Krinke T. Lapointe-Gagner M. and Buchwald JN. Side-to-side duodeno-ileal magnetic compression anastomosis: design and feasibility of a novel device in a porcine model. Surgical Endoscopy. 2023: 37: 6197-6207. https://doi.org/10.1007/s00464-023-10105-x.

References:

1. Comeau E, Gagner M, Inabnet W B, Herron D, M Quinn T M, Pomp A. Symptomatic internal hernias after laparoscopic bariatric surgery. Surgical Endoscopy. 2005; 19(1):34-39.
1. Stenberg E, Ottosson J, Magnuson A, et al. Long-term safety and efficacy of closure of mesenteric defects in laparoscopic gastric bypass surgery - A randomized clinical trial. JAMA Surgery. 2023;158(7):709-717. Doi:10.1001/jamasurg.2023.1042.
1. Brown W A, Ballesteros G P D. Ooi G, Higa K, Himpens J. Torres A, Shikora S, Know L, Herrera M F, IFSO appointed task force reviewing the literature on SADI-S/OADS. Obesity Surgery. 2021; 31:3-25, Diaz R, Davalos G, Welsh L K, Portenier D, Guerron A D. Surgical Endoscopy, 2019; Kallies K. Rogers A M. American Society for Metabolic and Bariatric Surgery Clinical Issues Committee. Surgery for Obesity and Related Diseases. 2020; 16:825-830.

SUMMARY OF CLINICAL INFORMATION

Table 10: Summary of Clinical Study

| Study Title | Creation of Side-to-Side Compression Anastomosis Using the GT Metabolic Solutions
Magnetic Anastomosis System (MAGNET System) to Achieve Duodeno-Ileostomy
Diversion in Adults with Obesity and with or without Type 2 Diabetes Mellitus: The
MAGNET Study |
|---------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Protocol Number / NCT Number: GTM-001 / NCT05322122 |
| Study Design | This is an operationally seamless, 2-stage, open-label, multicenter study enrolling up to 50
subjects at 5 study centers across Canada and Europe as follows:
Stage 1 first-in-human (FIH) and proof-of-concept with 5 subjects; and
Stage 2 feasibility with 45 subjects
All subjects in Stage 1 and 2 are followed for 12 months. |
| Study
Population | Adults (18 to 65 years of age, inclusive) with obesity (BMI 30-50) who meet one of the
following criteria: (1) have type 2 diabetes mellitus (T2DM) or experienced weight regain
following previous sleeve gastrectomy; (2) have T2DM without previous sleeve
gastrectomy; or (3) are candidates for a laparoscopic single anastomosis duodenal-ileal
bypass with sleeve (SADI-S) procedure and have BMI ≥ 40. |
| Primary and
Safety Endpoints | Primary: Feasibility/performance. The side-to-side anastomosis duodeno-
ileostomy will be considered feasible if results are successful at three months:
Placement of the MAGNET System (≥ 90% alignment of magnets); and
Passage of magnets without surgical re-intervention; and
Creation of a patent anastomosis, confirmed radiologically.
Safety: Incidence of treatment emergent AEs. |

A multi-center study was conducted to evaluate the feasibility/performance and safety of the MagDI System for the intended use in patients indicated for a side-to-side duodeno-ileal anastomosis. Forty-nine (49) subjects were treated across four (4) centers in Belgium, Canada, Republic of Georgia, and Spain.

Enrollment Criteria

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following inclusion criteria:

1. 18-65 years of age, inclusive, at the time of informed consent
1. BMI 30-50, inclusive with either:
- a. a. Previous-sleeve gastrectomy (> 12 months) with either T2DM (defined as HbAlc > 6.5%) or weight regain; or
- b. b. T2DM without previous gastrectomy; or
- c. c. Undergoing laparoscopic single anastomosis duodenal-ileal bypass with sleeve (SADIS) where duodeno-ileostomy is performed side to side with the MAGNET System and BMI ≥ 40
1. Agrees to refrain from any type of additional bariatric or reconstructive surgery that would affect body weight for 1 year
1. If a child-bearing female, subject must commit to not becoming pregnant and agree to use contraception for 1 year
1. Willing and able to comply with protocol requirements

Exclusion Criteria

Subjects eligible for enrollment in the study must meet none of the following exclusion criteria:

1. Type 1 diabetes
1. Use of injectable insulin
1. Uncontrolled T2DM
1. Uncontrolled hypertension, dyslipidemia or sleep apnea
1. Prior intestinal, colonic or duodenal surgery, other than bariatric
1. Prior surgery, trauma, prostheses, disease or genetic expression which prevent or contraindicate the procedure, including scarring and abnormal anatomy.
1. Refractory gastro-esophageal reflux disease (GERD)
1. Barrett's disease
1. Helicobacter pylori positive and/or active ulcer disease
1. Large hiatal hernia
1. Inflammatory bowel or colonic diverticulitis disease
1. Any anomaly precluding orogastric access by gastroscope and catheters, and manipulation techniques.
1. Implantable pacemaker or defibrillator
1. Psychiatric disorder, except well-controlled depression with medication for > 6 mo, or history of substance abuse
1. Woman who is either pregnant or breast feeding
1. Woman of childbearing potential who does not agree to use an effective method of contraception.
1. Any comorbidity or current status of subject's physiological fitness that in the surgeon's or anesthesiologist's opinion represents safety concerns that make the subject medically unfit for the procedure. This includes any conditions for which endoscopic or laparoscopic surgery would be contraindicated, and any significant congenital or acquired anomalies of the GI tract at or distal to the placement of the magnets.
1. Unhealed ulcers, bleeding lesions, turnor or any other lesion at target magnet deployment site
1. Expected need for MR imaging within the first 2 months after the procedure
1. Any anomaly preventing/contraindicating laparoscopic access and general laparoscopic procedures
1. Had surgical or interventional procedure within 30 days prior to procedure
1. Any scheduled surgical or interventional procedure planned within 30 days postprocedure
1. Any stroke/TIA within 6 months prior to consent
1. Requires chronic anticoagulation therapy (except aspirin)
1. Active infections requiring antibiotic therapy, unless resolved before undergoing the study procedure
1. Unable to comply with the follow-up schedule and assessments
1. Recent tobacco or nicotine product cessation within 21 years, that is, in adults on, or after their 22nd birthday.

POSTMARKET SURVEILLANCE

There is uncertainty regarding the generalizability of effectiveness of device use in the target U.S. patient population and regarding the incidence and severity of internal hernia. In order to satisfy special control (1) above FDA has determined a postmarket surveillance study is needed to provide additional information on the risk of internal hernia and bowel obstruction. There is uncertainty regarding this specific risk due to the study size consisting of 49 subjects, which may be insufficient to adequately characterize the risk's incidence and severity. Additionally, since the premarket clinical data involved primarily Caucasian, female subjects, there is uncertainty if the device can function as intended in the target U.S. patient population. Therefore, postmarket clinical data is necessary to collect information from demographic groups that had limited representation in the premarket study.

The postmarket study will assess and characterize incidence and severity of internal hernia and bowel obstruction in U.S. patients representative of the U.S. intended use population who are treated with the MagDI System for duodenal-ileal side-to-side anastomosis. The study will be conducted through an observational patient registry at U.S. centers and should include patients from demographic groups representative of the U.S. intended use population who had limited representation in the premarket study (e.g., African American. Asian) and have comorbidities similar to the intended use U.S. population. The study population will consist of U.S. patients, adults over the age of 21. who are willing to provide informed consent, indicated for a side-toside duodenal-ileal anastomosis, treated with the MagDI System, and with a BMI between 30-50 kg/m2. The sample size will include all consenting patients, who meet all inclusion and exclusion criteria at selected sites. Subjects will be enrolled within one year after the first enrollment, or until a clinically justified sample size to assess the primary endpoint has been reached. Data collection will be managed using an open-source electronic data system.

The primary endpoint will be the incidence and severity of internal hernia and small bowel obstruction at one year post-side duodeno-ileal anastomosis created with the MagDI System. Patients will be followed up for at least one year post-index procedure with additional follow up time-points as clinically indicated. The analysis will compare the incidence and severity of internal hernia and bowel obstruction to an appropriately justified comparator group.

LABELING

The labeling for the device is sufficient and satisfies the requirements of 21 CFR 801.109. The labeling consists of package labels and Instructions for Use (IFU). The labeling includes that the

device is intended for single use only, for sale only on order of a physician (Rx only) and is MR unsafe.

The IFU provides a description of the device, indications for use, directions for use, storage conditions, and known and probable risks. The labeling includes appropriate warnings, precautions, contraindications, and limitations of safety information including within the Instructions for Use : "The MagDIM System is an anastomotic surgical tool. The device has not demonstrated clinical effectiveness for weight loss or other underlying clinical procedures where a side-to-side duodeno-ileal anastomosis is indicated. The effects of this device on weight loss were not studied."

RISKS TO HEALTH

Table 19 below identified the risks to health that may be associated with use of a magnetic compression anastomosis system.

Risks to Health	Mitigation Measures
Inaccurate device placement leading to
unsuccessful anastomosis creation	Clinical performance testing
Postmarket surveillance
Animal performance testing
Non-clinical performance testing
Labeling
Anastomotic leaking, bleeding from
device decoupling	Clinical performance testing
Postmarket surveillance
Non-clinical performance testing
Labeling
Obstruction from
Internal hernia Device expulsion failure Anastomotic stricture/stenosis	Clinical performance testing
Postmarket surveillance
Labeling
Infection/sepsis	Clinical performance testing
Postmarket surveillance
Sterilization validation
Shelf life testing
Labeling
Adverse tissue reaction	Biocompatibility evaluation
Tissue damage (e.g., laceration, serosal
tear, inflammation, irritation)	Clinical performance testing
Postmarket surveillance
Animal performance testing
Labeling
Intestinal ulceration and/or scarring
from device migration	Clinical performance testing
Postmarket surveillance
Animal performance testing
Labeling

Table 19: Risks to Health and Mitigation Measures

| Gastrointestinal symptoms (e.g.,
abdominal distention, diarrhea,

constipation, nausea, vomiting)	Clinical performance testing Postmarket surveillance Animal performance testing Labeling
Interference with ferromagnetic
implants, devices, or objects	Non-clinical performance testing

SPECIAL CONTROLS

In combination with the general controls of the FD&C Act, the magnetic compression anastomosis system is subject to the following special controls:

(1) Premarket clinical performance testing and postmarket surveillance must demonstrate that the device performs as intended under anticipated conditions of use in the intended patient . population unless FDA determines based on the totality of the information provided for premarket review that data from postmarket surveillance is not required. Testing must:
- Demonstrate the ability to deliver the device to the target anatomic location and rate (1) of successful anastomosis creation:
- Evaluate all adverse events, including anastomotic leaking, bleeding, obstruction, (ii) infection/sepsis, pain, tissue damage, intestinal ulceration and/or scarring, and gastrointestinal symptoms; and
- Assess rate of successful device passage from the gastrointestinal tract. (iii)
(2) Animal performance testing must demonstrate that the device performs as intended under anticipated conditions of use. Testing must demonstrate the ability of the device to create an anastomosis supported by histology of the anastomosis site.
(3) Non-clinical performance data must demonstrate that the system performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
- Magnetic field strength testing to characterize safe distances from the magnets for (i) patients and users with ferromagnetic implants, devices, or objects; and
- (ii) Ability of the magnetic components to maintain adequate separation forces.
The patient-contacting components of the device must be demonstrated to be (4) biocompatible.
(5) Performance data must demonstrate the sterility of the patient-contacting components of the device.
Performance data must support the shelf life of the device by demonstrating continued (6) sterility of any sterile components and continued device functionality over the labeled shelf life.
(7) Labeling must include:

(i) A detailed summary of clinical performance testing conducted with the device, including study population, results, adverse events, and comparisons to any comparator groups identified:
(ii) Magnetic resonance compatibility information;
(iii) An expiration date or shelf life; and
A detailed summary of any post-market surveillance data collected and any (iv) necessary modifications to the labeling to accurately reflect outcomes based unon the postmarket data collected.

BENEFIT-RISK DETERMINATION

BENEFITS

The MagDI System is a compression anastomosis device using magnetic technology to achieve mechanical compression of two device housings. The device successfully created duodeno-ileal side-to-side anastomoses in 49/49 patients in the clinical study, which supports the effectiveness of an anastomotic tool claim. The clinical and animal data showed successful device placement through traditional minimally invasive techniques and instruments, supporting the probable benefit of functioning as an anastomotic tool. The in vivo verification data demonstrates that both magnet components may be positioned and docked together through intraluminal navigation or through an enterotomy. This data supports the probable benefit of flexible placement workflows. Finally, once wound strength is sufficient to maintain the anastomosis, both magnet components are expelled through the normal gastrointestinal pathway. This eliminates the need for device materials to remain in situ. In contrast to other anastomotic devices, such as sutures and staple devices, the subject device has the probable benefit of no long-term foreign body materials residing in the patient, which mitigates the risk of adverse and inflammatory tissue reactions that occur as the result of foreign body reactions.

The clinical study of 49 subjects consisted of largely Caucasian, obese, and female subjects and may not be adequately representative of the normal U.S. demographic make-up in terms of minority representation. There is uncertainty if the premarket data is representative of the intended U.S. patient population. Additional postmarket clinical data collection may mitigate these concerns contributing to uncertainty of benefit generalizability for this device type.

Risks

1. Stricture: 1/49 study subject was identified with an asymptomatic anastomotic stricture. Strictures are a known risk with anastomotic tools and devices. Adequate labeling informs physicians and patients of this risk, providing a mitigation for this risk.
1. Bowel obstruction and internal hernia: 1/49 study subject experienced an internal hernia resulting in a bowel obstruction, despite closure of the mesenteric defect. Due to the small clinical study size, it is unclear what the rate and severity are of the risk of internal hernia leading to bowel obstruction. leading to moderate uncertainty for this risk. Additional postmarket clinical data collection may reduce uncertainty of this risk.

1. Bowel injury: The study noted that bowel injuries (serosal tears) occurred during the intraluminal navigation of the magnet components into position due to manipulation of the tissue with laparoscopic graspers. The device or components were not directly involved with the injury.
1. Risks from concomitant procedure: Several AEs and SAEs were noted in the cohort receiving both a device anastomosis and concomitant sleeve gastrectomy. The AEs and SAEs associated with the gastrectomy procedure were not related to the subject device.
1. Risk of magnet technology, including dislodgement and effects on tissues/extraneous devices: Adequate bench testing has demonstrated appropriate magnet strength confirmed with animal and clinical testing, despite differences in tissue thickness. Additional contraindications are included to mitigate device interactions and to denote MRI-Unsafe. These risks have been adequately mitigated.
1. Risk of patient harm from infection: Low Risk and low uncertainty. Adequate sterility testing has be done to ensure sterility of the final finished product. Adequate sterility and reprocessing instructions are included for the device accessories. Additionally labeling is included to further mitigate this risk. This risk has been adequately mitigated.
1. Risk of patient harm from tissue interactions: Low Risk and low uncertainty. Adequate biocompatibility testing has demonstrated no unintended tissue effects or interactions from any of the device components. This risk has been adequately mitigated,

In summary, the premarket data demonstrates several probable benefits and risks when used in the creation of duodeno-ileal anastomoses. The risks of the MagDI System and clinical study limitations are mitigated by the special controls and labeling, However, since there is uncertainty regarding the generalizability of effectiveness of device use in the target U.S. patient population. and since there is uncertainty regarding the incidence and severity of internal hernia; postmarket data collection will be necessary. With the addition of postmarket data collection mitigating the uncertainties related to the premarket clinical data, the benefits outweigh the risks.

References:

1. Kaidar-Person O, Rosenthal RJ, Wexner SD, et al. Compression Anastomosis: History and Clinical Considerations. The American Journal of Surgery, 2008: 195: 818-826. https://www.doi.org/10.1016/j.amisurg.2007.10.006.
1. Tabola R. Cirocchi R. Fingerhut A. et al. A Systematic Analysis of Controlled Clinical Trials Using the NiTi CARTM Compression Ring in Colorectal Anastomoses. Tech Coloproctol. 2017; 21(3): 177-184. https://www.doi.org/10.1007/s10151-017-1583-2.
1. Buchberg BS, Masoomi H, Bergman H, et al. The Use of a Compression Device as an Alternative to Hand-Sewn and Stapled Colorectal Anastomoses: Is Three a Crowd? Journal of Gastrointestinal Surgerv. 2011: 15:304-310. https://www.doi.org/10.1007/s11605-010-1376-7.

Patient Perspectives

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

Benefit/Risk Conclusion

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

The GT Metabolic MagDI System is intended for use in the creation of side-to-side duodenoileal anastomoses in minimally invasive and laparoscopic surgery. Once wound strength is sufficient to maintain the anastomosis, the device is passed from the body. The effects of this device on weight loss were not studied.

The GT Metabolic MagDI System is intended for use in adult patients > 21 years.

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

CONCLUSION

The De Novo request for the MagDI™ System is granted, and the device is classified as follows:

Product Code: SAH Device Type: Magnetic compression anastomosis system Class: II Regulation: 21 CFR 878.4816