The Mucosal Integrity Conductivity Test System is indicated for use by gastroenterologists, surgeons, and medically trained personnel during an endoscopy to obtain a real time measurement of esophageal epithelial impedance. The device is not for use as a sole diagnostic screening tool.

Device Description

The Mucosal Integrity Conductivity (MI) Test System provides real-time measurements of alterations in esophageal evithelial integrity. The device is intended to aid in the evaluation of esophageal epithelial integrity by means of a balloon probe with direct electrical contact with the mucosal epithelium of the esophagus along with associated signal conditioning, hardware, and software for measuring and displaying information.

AI/ML Overview

The provided text describes the "Mucosal Integrity Conductivity (MI) Test System," an esophageal tissue characterization system. However, the document does not contain information about a study that assesses the device's performance against specific acceptance criteria using a test set of patient data or
human readers in a comparative effectiveness study. The "Performance Testing - Bench" section details benchtop tests of the device's physical properties and electrical measurement capabilities, but this is distinct from a clinical performance study using patient data.

The "Summary of Clinical Information" section briefly mentions two prospective clinical studies where the device was used in patients, noting its ability to measure esophageal mucosal impedance and the occurrence of few adverse events. However, these descriptions do not provide specific acceptance criteria, performance metrics (like sensitivity, specificity, accuracy), or details on how ground truth was established for diagnosis or classification of esophageal conditions based on the impedance measurements, which would typically be part of a study proving the device meets clinical acceptance criteria for its intended use as an aid in evaluation.

Therefore,Based on the provided text, I cannot answer all parts of your request as it does not detail a study that proves the clinical performance of the device against specific acceptance criteria for diagnostic accuracy or human-in-the-loop improvement for clinical decision making. The information focuses on bench testing, safety, and general functionality.

However, I can extract the acceptance criteria and performance for the benchtop performance tests.

Acceptance Criteria and Reported Device Performance (Benchtop Testing)

Here's a table summarizing the acceptance criteria and reported "Pass" results for the benchtop performance testing:

Test	Acceptance Criteria	Reported Device Performance
Balloon Functionality Testing
Double Wall Thickness	.00045" +/- .00025"	Pass
Compliance Diameter @ 0.5atm	20 mm +/- .65 mm	Pass
Burst Pressure	2.04 atm minimum	Pass
Dimensional Design Verification Testing
Probe Overall Length	55.25" +/- 2.0"	Pass
Probe, Balloon Diameter when Inflated	2.0 cm +/- 0.1 cm	Pass
Probe Weight	2.8 oz. +/- 0.5 oz.	Pass
Bond between Sensors and Balloon Testing
Adhesive Strength after Exposure to Saline	≥ adhesive strength without saline exposure2.267 lbf	Pass
Tensile Strength, Distal Tip to Catheter of MI Probe
Tensile Strength Distal Tip Joint MI Probe (Initial)	≥ 3.0 lbf based on independent study	Pass
Tensile Strength Distal Tip Joint MI Probe (Added to Submission)	≥ 4.5 lbf from EN 1617 (20 Newtons)	Pass
Impedance Measurements of MI Probe Sensors
Impedance Measurement Accuracy	174+/- 100 Ohms	Pass
Impedance Signal Noise	< 20 Ohms	Pass
Impedance Thermal Stability	+/- 100 Ohms	Pass
Impedance Temporal Stability	+/- 100 Ohms	Pass

Since the document primarily describes benchtop performance and safety testing, and general clinical use observations rather than a clinical performance study with diagnostic accuracy outcomes, the following information is not available or not applicable based on the provided text:

Sample size used for the test set: Not specified for a clinical performance test set. The bench tests specify n=10 for balloon functionality, n=33 for some dimensional tests, n=1 for impedance accuracy tests, and n=4 or n(g) for tensile strength.
Data provenance (e.g. country of origin of the data, retrospective or prospective): The clinical studies mentioned are stated to be "prospective," but no country of origin is specified for the data.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not specified for any clinically relevant ground truth.
Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not specified.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance: No such study is mentioned or implied, as the device gives a direct measurement and is not described as an AI assistance tool for human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: The device directly measures impedance, it's not described as an algorithm making a diagnostic decision in a standalone fashion. Its purpose is to obtain a real time measurement to aid in the evaluation.
The type of ground truth used (expert consensus, pathology, outcomes data, etc): While one clinical study mentions patients with "active eosinophilic esophagitis (EoE, confirmed with pathology)," the document doesn't explicitly state that pathology was used as the ground truth for evaluating the device's performance against specific clinical endpoints derived from impedance measurements. The device simply measured impedance in these patients.
The sample size for the training set: Not applicable as there's no mention of a machine learning model requiring a training set for diagnostic classification in the provided text.
How the ground truth for the training set was established: Not applicable.

Summary

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DE NOVO CLASSIFICATION REQUEST FOR MUCOSAL INTEGRITY CONDUCTIVITY (MI) TEST SYSTEM

REGULATORY INFORMATION

FDA identifies this generic type of device as the following:

Esophageal tissue characterization system. An esophageal tissue characterization system is a device intended for obtaining measurement of electrical properties within esophageal tissue.

NEW REGULATION NUMBER: 21 CFR 876.1450

CLASSIFICATION: Class II

PRODUCT CODE: QIS

BACKGROUND

DEVICE NAME: Mucosal Integrity Conductivity (MI) Test System

SUBMISSION NUMBER: DEN180067

DATE DE NOVO RECEIVED: December 20, 2018

CONTACT:

Diversatek Healthcare, Inc. 102 East Keefe Avenue Milwaukee, WI 53212

INDICATIONS FOR USE

LIMITATIONS

The sale, distribution, and use of the Mucosal Integrity Conductivity (MI) System are restricted to prescription use in accordance with 21 CFR 801.109.

The MI Test System should be used as directed in the labeling to avoid adverse interaction within the esophagus.

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

DEVICE DESCRIPTION

The patient undergoing an esophageal mucosal impedance study will first have an endoscope placed with the distal end of the scope proximal to the area under study. The MI Probe is advanced into the patient's esophagus by guiding it alongside the endoscope. The MI Probe is positioned under visual guidance using the optics of the endoscope. The probe also contains proximal markings on the catheter portion outside the patient to aid in positioning. The total time of deployment for collecting mucosal impedance values is expected to be less than 5 minutes. Figure 1 shows the MI Probe and its components along with its inflated and deflated state.

Image /page/1/Figure/4 description: The image shows three different views of a medical device. The first image shows the device inflated, with labels pointing to the distal esophagus, sensor column (10 cm), and proximal esophagus. The second image shows the device deflated, and the third image shows the device inflated again.

Figure 1. Inflated and Deflated Probe.

The impedance values are transmitted from the MI Probe to the non-patient contacting MI Adapter as standard impedance signals, measured, converted to digital data and are then transmitted to the Central Unit via the MI Cable. The Central Unit then transfers the processed data to the PC for display and analysis through the MI Software. This data is displayed through the use of a color map for easy identification of impedance values. The color map displays realtime impedance measurements for the duration of the individual study, and results are reported as both raw data and a summary.

The inflation and deflation of the probe is controlled via the MI Inflator Gauge Box, which has a pressure gauge to display the pressure within the balloon. The components are illustrated in

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Figure 2 below. The impedance values are transmitted from the MI Probe to the non-patient contacting MI Adapter as standard impedance signals, measured, converted to digital data and are then transmitted to the Central Unit via the MI Cable. The Central Unit then transfers the processed data to the PC for display and analysis through the MI Software. This data is displayed through the use of a color map for identification of impedance values. The color map displays real-time impedance measurements for the duration of the individual study, and results are reported as both raw data and a summary.

Image /page/2/Figure/1 description: The image shows a medical device called an MI Inflator Gauge Box, along with its various components. The components include an inflator, a cable, an air supply line to the probe, an MI adapter module, and an MI probe. The image also shows an inflated balloon of the MI probe with the sheath removed. The MI Inflator Gauge Box appears to be the central control unit for the device.

Figure 2. The complete MI System with all components aside from the Central Unit

SUMMARY OF NONCLINICAL/BENCH STUDIES

Non-clinical/bench studies conducted on the MI Test System to demonstrate a reasonable assurance of safety and effectiveness of the device are summarized below.

REPROCESSING

As illustrated in Figure 3 below, the MI Probe makes direct patient contact and is connected to reusable components that do not make direct patient contact. Those reusable components will be manipulated by the user at the same time they are using the patientcontacting probe, thereby making cross-contamination between the probe and the reusable components possible. This risk was addressed by the inclusion of validated reprocessing instructions in the labeling for the reusable components.

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Image /page/3/Figure/0 description: The image shows a diagram of a system with several components. The components include an MI Probe, MI Probe Cable, Inflator Gauge Box, MI Adapter for Central Unit, Cable for Central Unit, Central Unit (inSIGHT Ultima), USB, and a Computer running System software (Zvu adapted for MI). The diagram also indicates the areas of patient contact, clinician, and technician.

Figure 3. Diagram of patient contacting and non-patient contacting components. This involved the use of cleaning instructions and disinfection instructions per FDA's 2015 reprocessing guidance document, "Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling". The instructions for the MI Test System provide step-by-step instructions for the user to first clean and then low-level disinfect the reusable components using a Sani-Cloth wipe.

The instructions indicate that reprocessing should occur immediately following use, they include the words "thoroughly clean," they provide endpoints for each step (i.e., visibly clean for cleaning and contact time of 2 minutes per wipe manufacturer's instructions for disinfection), they include a visual inspection step following cleaning and state that the user should repeat the cleaning steps if still visibly dirty, and they include drying steps post-cleaning and disinfection.

Furthermore, the reuse inspection instructions to indicate that the user should inspect the device for damage, corrosion, cuts, punctures, and cracked seals following cleaning and disinfection.

SOFTWARE

Software documentation was provided in accordance with the FDA Guidance Document, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices," (issued May 11, 2005) for a Moderate Level of Concern (LOC). A Moderate LOC is deemed appropriate as malfunction of the device software or a latent design flaw in the device software may lead to a delay in the delivery of appropriate medical care, which would likely result in minor injury, but would likely not result in serious injury or death due to the availability of other patient vital signs.

Cybersecurity information was provided in accordance with the FDA Guidance Document, "Content of Premarket Submissions for Management of Cybersecurity in Medical Devices - Guidance for Industry and Food and Drug Administration Staff" (issued October 02, 2014).

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BIOCOMPATIBILITY/MATERIALS

The MI Test System is classified as mucosal membrane contacting for repeat, prolonged contact during clinical use (< 24 hours). The MI Probe was evaluated according to the FDA guidance (2016). "Use of International Standard ISO 10993-1. Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process," and the following biocompatibility endpoints were assessed for the MI Test System:

Cytotoxicity .
Sensitization .
Irritation .

Results support the biocompatibility of the MI Test System.

ELECTRICAL SAFETY AND ELECTROMAGNETIC COMPATIBILITY (EMC)

The test reports address the basic safety evaluation (which includes electrical safety testing) per the FDA-recognized standard IEC 60601-1:2005 + A1:2012. In addition, the EMC testing was conducted per IEC 60601-1-2:2007 and passed the applicable clauses. The results support the electrical safety and EMC of the device.

PERFORMANCE TESTING - BENCH

The integrity and performance of the MI Test System were evaluated with the nonclinical testing summarized in the tables below.

Test	Acceptance Criteria	Diversatek HealthcareTest Article Result
Double Wall Thickness	.00045" +/- .00025"	(b)(4)Pass
ComplianceDiameter @ 0.5atm	20 mm +/- .65 mm	(b)(4)Pass
Burst Pressure	2.04 atm minimum	(b)(4)Pass

Table 13.1 Balloon Functionality Testing Summary

Sample size of the tests above are n=10. The double wall thickness and compliance diameter was measured using digital height gauge.

A hydraulic burst tester was used to record the balloon burst pressure (n=10), and the compliance of the diameter of the balloons at 0.5 atm was measured with a ruler.

Table 13.3 Dimensional Design Verification Testing Summary
Test	Acceptance Criteria	Diversatek HealthcareTest Article Result

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Probe Overall Length	55.25" +/- 2.0"	(b)(4)
		Pass
Probe, Balloon Diameter when Inflated	2.0 cm +/- 0.1 cm	(b)(4)
		Pass
Probe Weight	2.8 oz. +/- 0.5 oz.	(b)(4)
		Pass

Dimensional verification test for the probe overall length, probe-balloon inflated diameter (n=33) were measured using a ruler, and the probe weight was measured with a digital scale.

Table 13.4 Bond between Sensors and Balloon Testing Summary

Test	Acceptance Criteria	Diversatek HealthcareTest Article Result
Adhesive Strength afterExposure to Saline	≥ adhesive strengthwithout saline exposure2.267 lbf	(b)(4)Pass

were prepared by (b) (4) For the Adhesive Strength test, samples(b) (4)

Table 13.5 Tensile Strength, Distal Tip to Catheter of MI Probe

Test	Acceptance Criteria	Diversatek HealthcareTest Article Result
Tensile Strength DistalTip Joint MI Probe	≥ 3.0 lbf based onindependent study	(b)(4)Pass
Tensile Strength DistalTip Joint MI Probe	Added to this Submission:≥ 4.5 lbf from EN 1617 (20Newtons) for max breakforce of sterile drainagecatheters	(b)(4)Pass

An initial pull test (ng) on the distal tip joint of the MI Probe, where a (b) (4)
acceptance criteria was used. Another test (n=4) was then conduced in accorduced in accordu was then conduced in accordance with le Drainage Catheters and Accessory Devices for Single Use with a (b) (4) acceptance criteria. In both tests, the joints were pulled until the point of failure and the maximum tensile strength of the joints was recorded. All breakages happened either at the distal tip or on the balloon material of the sample.

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Test	Acceptance Criteria	Diversatek HealthcareTest Article Result
ImpedanceMeasurement Accuracy	174+/- 100 Ohms	(b)(4)Pass
Impedance Signal Noise	< 20 Ohms	(b)(4)Pass
Impedance ThermalStability	+/- 100 Ohms	(b)(4)Pass
Impedance TemporalStability	+/- 100 Ohms	(b)(4)Pass

Table 13.6 Impedance Measurements of MI Probe Sensors

To demonstrate impedance measurement accuracy in bench testing, a single probe was placed in b)(41% saline (which had ab)(4) ohms impedance measurements from all ten sensors on the probe were then recorded over the course of 1 minute via analog-to-digital (A/D) counts (The MI Adapter can function as an analog-to-digital converter, which converts the voltage or current into a digital number). The average measurement was(b) (4) Ohms, which is within the acceptance criteria (shown above).

The impedance signal noise was measured by setting the MI software to report the maximum and minimum A/D counts for each channel on each probe for a period of 1 second. The differences between the minimum and maximum A/D counts for every channel was then calculated.

For the impedance thermal stability and impedance temporal stability, the software was set to report the average A/D counts for each channel of each MI probe sensor still in in saline over a 1 minute period and 5 minute period respectively. For both tests the average resistance values were taken after 1 minute in room temperature saline and were compared to the impedance after 1 minute in body temperature saline (for thermal stability) and 5 minutes in room temperature saline (for the temporal stability).

Only one probe was tested for the impedance measurement tests. All sensors were tested on the probe.

SUMMARY OF CLINICAL INFORMATION

Clinical data from the sponsor was used to support the safety and effectiveness of the device. The clinical information also supported the benefit-risk determination.

The first prospective study was performed on "" patients undergoing esophagogastroduodenoscopy, with or without wireless pH monitoring. Some patients had symptoms of GERD (erosive esophagitis or abnormal pH testing. n = 24) or active eosinophilic esophagitis (EoE, confirmed with pathology at both distal and proximal esophagus, n = 21); there were also patients with normal esophagogastroduodenoscopy (EGD) and pH testing (n = 24). The study results show that the device was able to measure the esophageal mucosal impedance in ohms for all 0149 patients. There was only one reported adverse event (a chest pain unrelated to the device) and there was no follow-up of the patients after the procedure ended.

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Another prospective study was conducted with the subject device in a population that consisted of 23 adult patients with EoE, of whom 18 patients had > 15 eosinophils per high-power field (eos/HpF), and 5 patients had inactive EoE (4 patients were effectively treated with budesonide and 1 with omeprazole). There were 10 additional control patients consisting of 8 adults undergoing endoscopy for clinically-indicated Bravo capsule placement for assessment of GERD, and 2 patients were undergoing endoscopy for evaluation of possible celiac disease. The study results show that the MI Test System was able to measure the esophageal mucosal impedance in ohms for all 23 patients. There were no reported adverse events and there was no follow-up of the patients after the procedure ended.

Pediatric Extrapolation

In this De Novo request, existing clinical information was not leveraged to support the use of the device in pediatric patient population

LABELING

The labeling comprises physician labeling that includes the device indications for use, a description of the device, warnings, and precautions, clinical data on the device, and instructions for the safe and effective use of the device. The labeling satisfies the requirements of 21 CFR 801.109 Prescription devices.

Per the special controls for this generic type of device, labeling includes the following:

Specific instructions regarding proper placement and use of the device. ●
. An expiration date and shelf life for single use components.
. Reprocessing instructions for the reusable components.

RISKS TO HEALTH

The table below (Table 4) identifies the risks to health that may be associated with use of the esophageal tissue characterization system and the measures necessary to mitigate these risks.

Identified Risks to Health	Mitigation Measures
Device Malfunction Related to:	Non-clinical performance testing
• Breaking	Shelf life testing
• Fractures	Software verification, validation, and hazard
• Unintentional separation of components	analysis
• Inaccurate reading	Labeling
• Failure to sense
• Endoscope incompatibility
Adverse tissue reaction	Biocompatibility evaluation

Table 4: Identified Risks to Health and Mitigation Measures

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Electrical shock and electrical interferencefrom other devices	Electrical safety testingElectromagnetic compatibility (EMC) testingLabeling
Procedural risks (which may includeprocedures of endoscopy with sedation)	Labeling
Infection/cross-contamination	Reprocessing validationLabeling

SPECIAL CONTROLS

In combination with the general controls of the FD&C Act, the esophageal tissue characterization system is subject to the following special controls:

(1) All patient contacting components of the device must be demonstrated to be biocompatible.
(2) Performance testing must demonstrate the mucosal impedance system can accurately measure the designated electrical characteristics.
(3) Mechanical safety testing must demonstrate that the device will withstand forces encountered during use.
(4) Software verification, validation, and hazard analysis must be performed.
(5) Electromagnetic compatibility and electrical safety, mechanical, and thermal safety testing of the device must be performed.
(6) Performance data must validate the reprocessing instructions for any reusable components of the device.
(7) Labeling must include:
- Specific instructions regarding the proper placement and use of the device; (i)
- (ii) Instructions for reprocessing of any reusable components; and
- (iii) An expiration date for single use components.

BENEFIT-RISK DETERMINATION

The probable benefits of the device are based on the ability to obtain the electrical characteristic of the esophageal tissue. In the case of the MI Test System, the device can be used by gastroenterologists, surgeons, and medically trained personnel during an endoscopy to obtain a real time measurement of esophageal epithelial impedance. This information as an adjunct to standard clinical practice can provide the clinician with information to assist in making a more informed decision for patient care.

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The probable risks of the device include the risks associated with endoscopy and sedation, device malfunction, adverse tissue reaction, electrical shock and electrical interference, and crosscontamination or infection. Device-related adverse events were not reported in the clinical studies. The risk of device malfunctions includes the risk of inaccurate reading which could result in an incorrect determination by the clinician.

Based on the available performance data, the probability of such harmful events is low, and the incidence is reduced with the mitigation measures and special controls identified above.

The probable benefits of the device outweigh the probable risks.

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 probable benefits outweigh the probable risks for the MI Test System. The device provides benefits, and the risks can be mitigated using general controls and the identified special controls.

CONCLUSION

The De Novo request for the Mucosal Integrity Conductivity Test System is granted and the device is classified as follows:

Product Code: QIS Device Type: Esophageal tissue characterization system Regulation Number: 21 CFR 876.1450 Class: Class II

Regulation Number and Section

§ 876.1450 Esophageal tissue characterization system.

(a)
Identification. An esophageal tissue characterization system is a device intended for obtaining measurements of electrical properties within esophageal tissue.(b)
Classification. Class II (special controls). The special controls for this device are:(1) All patient contacting components of the device must be demonstrated to be biocompatible.
(2) Performance testing must demonstrate the device can accurately measure the designated electrical characteristics.
(3) Mechanical safety testing must demonstrate that the device will withstand forces encountered during use.
(4) Software verification, validation, and hazard analysis must be performed.
(5) Electromagnetic compatibility and electrical safety, mechanical safety, and thermal safety of the device must be performed.
(6) Performance data must validate the reprocessing instructions for any reusable components of the device.
(7) Labeling must include:
(i) Specific instructions regarding the proper placement and use of the device;
(ii) Instructions for reprocessing of any reusable components; and
(iii) An expiration date for single use components.