The Exalenz BreathID® Hp Lab System or Exalenz BreathID® Smart System is intended for use to non-invasively measure changes in the 13CO2/12CO2 ratio of exhaled breath, which may be indicative of increased urease production associated with active Helicobacter pylori (H. pylori) infection in the stomach.

The Exalenz BreathID® Hp Lab System or Exalenz BreathID® Smart System is indicated for use as an aid in the initial diagnosis and post treatment monitoring H. pylori of infection in adult patients ages 3-17 years old. The Exalenz BreathID® Hp Lab System consists of the appropriate IDkit Hp™ kit, and the BreathID® Hp device, Auto Sampler and Lab Application. The Exalenz BreathID® Smart System consists of the appropriate IDkit: Hp™ kit and the BreathID® Smart device.

To be administered by trained personnel as ordered by a licensed healthcare practitioner.

Device Description

The Modified BreathID® Hp Lab System, with the trade name BreathID® Smart, is a noninvasive breath test system for detecting the presence of Helicobacter pylori (H. pylori). The system consists of an electro-optical medical device with embedded software designed to measure and compute the changes in ratio between 13CO2 and 12CO2 concentrations in the patient's exhalation, an integrated Auto Sampler, integrated software, and a test kit.

The IDkit Hp™ Two test kit consists of:

A 75mg 13C-urea tablet ●
A 4.3g package of powdered Citrica (citric acid) ●
Drinking straw
Package Insert (Instructions for Use) ●
2 Breath Sample Bags (Baseline and Post Ingestion) with bar code labels ●
A large Sample Transport Bag

Using bags for breath collection enables off site and deferred testing as well as testing of multiple breath sample bags sequentially in a batch. The BreathID® Smart System measures and computes the ratio between 13CO2 and 12CO2 in the patient's exhaled breath before and after the ingestion of 13C-urea. The change in the 13CO2 / 12CO2 ratio before and after ingestion of 13C-urea is used to compute the Delta over Baseline (DOB).

The 13C measurement method for both the subject and the cleared (predicate) versions of the BreathID® Hp Lab Systems is based on Molecular Correlation Spectroscopy™ (MCS) technology. MCS technology is based on the concept of optical absorption of specific radiation emitted from CO2 discharge lamps.

AI/ML Overview

The provided text describes the regulatory clearance of the BreathID® Smart System as substantially equivalent to the BreathID® Hp Lab System (predicate device). The Special 510(k) submission focuses on a modified configuration of the predicate device, integrating three existing stand-alone components into one. The performance testing section primarily addresses verification and validation of the modified system, rather than a clinical study establishing diagnostic performance against a ground truth for a novel device.

Therefore, the information regarding acceptance criteria and a study proving the device meets those criteria is geared towards demonstrating equivalence to the predicate device in terms of performance characteristics, not a primary diagnostic accuracy study.

Here's the breakdown of the information that can be extracted from the provided text, along with what is not available given the nature of this document (a 510(k) summary for a modified device):

1. A table of acceptance criteria and the reported device performance

The document mentions that all predefined acceptance criteria were met but does not explicitly list the quantitative acceptance criteria for most tests, beyond the cutoff point for detection. The tests described are primarily engineering and analytical validation tests comparing the new device to the predicate, rather than a clinical diagnostic accuracy study.

Acceptance Criteria (Implicit/Explicit)	Reported Device Performance
Precision Tests: Within laboratory precision/repeatability	Not explicitly stated, but "All the pre-defined acceptance criteria were met" for accurate and repeatable results over time.
Reproducibility Test: Between devices	Not explicitly stated, but "All the pre-defined acceptance criteria were met" for accurate and repeatable results over time.
Sample Carry-Over Test: No sample carry-over effect	"The carry-over test was designed to demonstrate that the system has no sample carry-over effect." (Implies acceptance criteria met)
Environmental Tests: Performance within specified transportation, storage, and operating conditions (temperature, altitude, vibrations, drop tests)	"The BreathID® Smart system was functionality tested several times during the Environmental test and found within the acceptance criteria."
Comparison to Predicate (Interchangeability): BreathID® Smart System performance is statistically comparable to BreathID® Hp Lab System	"A comparison test... statistically shows that both systems may be used interchangeably."
Electrical Safety and Electromagnetic Compatibility (EMC)	Not explicitly stated, but implies compliance as "All the pre-defined acceptance criteria were met."
H. pylori Detection Cut-off Point: 5.0 DOB per mil (post dose minus pre dose)	Not a performance metric of this study, but the same cut-off point as the predicate device.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample Size for Comparison Test: 80 measurements were performed on each system (BreathID® Hp Lab System and BreathID® Smart System).
Data Provenance: The tests used "contrived gases simulating different levels of 13CO2". This indicates these were bench tests using simulated samples, not human patient data. The country of origin of this specific test data is not provided, but the applicant's address is in Israel.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not Applicable / Not Provided: For the performance tests described (precision, reproducibility, carry-over, environmental, and comparison using contrived gases), expert interpretation of patient samples was not required to establish ground truth. The "ground truth" for these tests would be the known concentration of the simulated gases.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

None: Adjudication methods are typically relevant for clinical studies where multiple experts interpret patient data to establish a definitive diagnosis. The described tests used direct measurement of simulated gas concentrations and engineering validation, which do not involve expert adjudication.

5. 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 MRMC Study: This document does not describe an MRMC study. The device measures a chemical ratio in breath; it is not an imaging device or AI-assisted diagnostic tool that would involve human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Not Applicable: The device is a diagnostic system that provides a numerical output (DOB) and a positive/negative determination based on a predefined cut-off. It is inherently a standalone measurement system, but the term "standalone performance" often refers to an AI algorithm's performance without human interaction. This device is an instrument, not an AI algorithm in the traditional sense, though it does have embedded software. The performance testing focuses on the system's ability to accurately measure 13CO2/12CO2 ratios.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

Known/Contrived Gas Concentrations: For the described performance tests, the "ground truth" for the test set was created using "contrived gases simulating different levels of 13CO2". This means the expected 13CO2 concentrations were known and controlled by the experimenters.

8. The sample size for the training set

Not Applicable / Not Provided: The device is an instrument for measuring a specific chemical ratio, not a machine learning or AI model that requires a training set in the conventional sense. Its functionality is based on molecular correlation spectroscopy an established technology.

9. How the ground truth for the training set was established

Not Applicable: As there's no "training set" in the context of an AI model, there's no ground truth establishment for such a set. The device's operation is based on physical principles of spectrometry and a defined chemical reaction.

Summary

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February 6, 2020

Exalenz Bioscience Ltd. Raffi Werner CEO 4 Ha'Maayan st. Modiin. 7177872 IL

Re: K193610

Trade/Device Name: BreathID Smart System Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus serological reagents Regulatory Class: Class I, reserved Product Code: MSO, JJO Dated: December 22, 2019 Received: December 26, 2019

Dear Raffi Werner:

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

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Ribhi Shawar, Ph.D. (ABMM) Chief, General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K193610

Device Name

BreathID® Hp Lab System or BreathID® Smart System

Indications for Use (Describe)

To be administered by trained personnel as ordered by a licensed healthcare practitioner.

Type of Use (Select one or both, as applicable)

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

Purpose of this 510(k):

The primary purpose of this Special 510(k) submission is to clear a modified configuration of the already cleared BreathID® Hp Lab System (K173777) which has the same Intended Use and Indication for Use. The modified configuration combines the three existing stand-alone components of the BreathID® Hp Lab System into one integrated device.

Applicant's Name

Exalenz Bioscience Ltd. 4 Ha'Maayan Street Modiin, 7177872, Israel Tel: +972-8-9737502 Fax: +972-8-9737501

Contact Person

Raffi Werner Exalenz Bioscience Ltd. 4 Ha'Maayan Street Modiin, 7177872, Israel Tel: +972-8-9737502 Fax: +972-8-9737501 raffiw(@exalenz.com

Date Prepared

Jan 29, 2020

Trade Name

BreathID® Smart System

Classification Name

Test, urea (breath or blood)

Product Code

MSQ, JJQ

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Device Class

Regulation Number

866.3110

Panel

Microbiology

Predicate Device

Exalenz BreathID® Hp Lab System [Exalenz Bioscience Ltd.] cleared under K173777

Device Description

The IDkit Hp™ Two test kit consists of:

A 75mg 13C-urea tablet ●
A 4.3g package of powdered Citrica (citric acid) ●
Drinking straw
Package Insert (Instructions for Use) ●
2 Breath Sample Bags (Baseline and Post Ingestion) with bar code labels ●
A large Sample Transport Bag

The 13C measurement method for both the subject and the cleared (predicate) versions of the BreathID® Hp Lab Systems is based on Molecular Correlation Spectroscopy™ (MCS)

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technology. MCS technology is based on the concept of optical absorption of specific radiation emitted from CO2 discharge lamps.

Intended Use / Indication for Use

The Exalenz BreathID® Hp Lab System or Exalenz BreathID® Smart System is intended for use to non-invasively measure changes in the 1300/12CO2 ratio of exhaled breath, which may be indicative of increased urease production associated with active Helicobacter pylori (H. pylori) infection in the stomach.

The Exalenz BreathID® Hp Lab System or Exalenz BreathID® Smart System is indicated for use as an aid in the initial diagnosis and post treatment monitoring of H. pylori infection in adult patients and pediatric patients ages 3-17 years old. The Exalenz BreathID® Hp Lab System consists of the appropriate IDkit Hp™ kit, and the BreathID® Hp device, Auto Sampler and Lab Application. The Exalenz BreathID® Smart System consists of the appropriate IDkit: Hp™ kit and the BreathID® Smart device.

To be administered by trained personnel as ordered by a licensed healthcare practitioner.

Substantial Equivalence

The following table summarizes the data on the Exalenz BreathID® Smart System (subject of this 510(k) submission) and compares to the Exalenz BreathID® Hp Lab System cleared under K173777 (the predicate device).

Device & Predicate Device(s):	BreathID® Smart System(The Subject Device)	BreathID® Hp Lab System(The Predicate Device)
Device Trade Name	BreathID Smart System	BreathID Hp Lab System
General DeviceCharacteristic Similarities
Intended Use/Indications forUse	The Exalenz BreathID SmartSystem is intended for use tonon-invasively measure changesin the 13CO2/12CO2 ratio ofexhaled breath, which may beindicative of increased ureaseproduction associated withactive Helicobacter pylori (H.pylori) infection in the stomach.	The Exalenz BreathID Hp LabSystem is intended for use tonon-invasively measure changesin the 13CO2/12CO2 ratio ofexhaled breath, which may beindicative of increased ureaseproduction associated withactive Helicobacter pylori (H.pylori) infection in the stomach.
Device & Predicate Device(s):	BreathID® Smart System( The Subject Device )	BreathID® Hp Lab System( The Predicate Device )
	The Exalenz BreathID® Smart System is indicated for use as an aid in the initial diagnosis and post treatment monitoring of H. pylori infection in adult patients and pediatric patients ages 3-17 years old. The Exalenz BreathID® Smart System consists of the appropriate IDkit: Hp™ kit and the BreathID® Smart device.To be administered by trained personnel as ordered by a licensed healthcare practitioner.	The Exalenz BreathID® Hp Lab System is indicated for use as an aid in the initial diagnosis and post treatment monitoring of H. pylori infection in adult patients and pediatric patients ages 3-17 years old. The Exalenz BreathID® Hp Lab System consists of the appropriate IDkit Hp™ kit, and the BreathID® Hp device, Auto Sampler and Lab Application.To be administered by trained personnel as ordered by a licensed healthcare practitioner.
Test Sample	Human breath exhaled into breath sample bags	Same
Sample Collection Method	Two breath sample bags: for baseline and post ingestion	Same
Organism	Helicobacter pylori	Same
Reagent	13C Urea (NDA 21-314)	Same
Test Duration	15 – 20 minutes	Same
Detection Method	Measuring levels of 13CO2 and 12CO2 the spectroscopy	Same
Test Output (Reported Result)	DOB of the 13CO2 / 12CO2 ratio before and after ingestion of 13C Urea	Same
Cut-off Point	5.0 DOB per mil (post dose minus pre dose)	Same
General DeviceCharacteristic Differences
System Hardware Components	• BreathID® Smart device• IDkit Hp Two test kit	• BreathID® Hp device• Auto Sampler• IDkit Hp Two test kit• PC
System Software Components	• BreathID® Smart device embedded SW	• BreathID® Hp Lab embedded SW• BreathID Hp Lab Application• Auto Sampler embedded SW

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Comparison of Intended Use

The intended use of the modified BreathID® Hp Lab System, (to include the BreathID® Smart System) has essentially remained equivalent to the predicate; both are intended for the initial diagnosis and post treatment monitoring of H. pylori infection in adult and pediatric (ages 3-17 years old) patients, and both are prescription devices are designed for performing multiple 13002 based breath tests automatically one after the other. But while the cleared BreathID Hp Lab system has an external auto sampler which enables sequential testing of 10 pairs of Breath Sample bags, the BreathID Smart analyzer includes an integrated auto sampler that enables sequential testing of 4 pairs of Breath Sample bags. These pairs are measured sequentially and automatically as in the predicate BreathID® Hp Lab System.

Test Kit and Ingested Drug

The BreathID® Smart System and the predicate BreathID® Hp Lab System both use the same IDkit Hp™ Two kit that consists of 13C urea, approved in NDA 21-314, and breath collection bags, approved in K162150. The protocol for breath collection and ingestion of 13C urea remains unchanged.

Comparison of Technological Characteristics

The BreathID® Smart System shares with its predicate device the same measurement . system based on the same technology, the same test kit, the same test substrate, and the same diagnostic capabilities. Both the subject and predicate systems use the MCS technology (Molecular Correlation Spectroscopy) and measure the ratio of 13 CO2/1CO2 in exhaled breath prior to and after administration of the test substrate (13C-Urea). The MCS technology measures the light absorbance by infrared spectrometry, which is correlative to CO2 concentration in the breath sample. The output result in both systems is the Delta Over Baseline (DOB) and a positive/negative determination is based on the same assay cut-off (>5 DOB).
The predicate device includes an analyzer which is connected to an external auto sampler, . enabling automatic and sequential testing of 10 pairs of breath sample bags. The modified device is based on the same analyzer as the predicate, with an integrated auto sampler, enabling four pairs of breath sample bags to be measured automatically and sequentially.

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The predicate device includes an external computer component to run the BreathID Lab ● Application software that communicates with the BreathID analyzer and external auto sampler. In the modified device, the computer and application software are built into the BreathID analyzer.

Summary of Performance Testing

Exalenz has performed extensive and well executed verification and validation to verify the performance of the BreathID® Smart System. The verification and validation testing program for the BreathID Smart system was designed based on the device specifications and requirements, as well as on the associated potential risks, as identified and evaluated in the risk analysis and in accordance with FDA recognized standards.

Software Verification and Validation

Software testing was conducted to evaluate the performance of the subject system and to verify that it performs according to its software requirements. Verification involved functionality testing, timing analysis, integration with the hardware, and error detection and handling. Verification was achieved by design reviews, code walkthroughs, functional testing of subcomponents and integration testing with the hardware.

System Performance and Safety Testing

The performance bench testing program consisted of the following tests:

. Precision Tests (Precision, Repeatability and Reproducibility). Precision testing focused on the within laboratory precision/repeatability of the system and used one device, while the reproducibility test used 3 devices.
Sample Carry-Over Test. The carry-over test was designed to demonstrate that the . system has no sample carry-over effect.
Environmental Tests (transportation, storage and operating conditions). The specified . transportation, storage and operating conditions of the BreathID® Smart Device are identical to those of the predicate system. The environmental tests included temperature and altitude end conditions, vibrations and drop tests. The BreathID® Smart system was functionality tested several times during the Environmental test and found within the acceptance criteria.

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Comparison test between the predicate BreathID® Hp Lab System and the BreathID® . Smart System. A comparison test between the predicate system and the device subject of this submission ran 80 measurements on each system and statistically shows that both systems may be used interchangeably.
Electrical safety and electromagnetic compatibility (EMC) .

The above tests used contrived gases for simulating different levels of 13CO2 as a result of H. pylori infection. All the pre-defined acceptance criteria were met; therefore, it can be concluded that the BreathID® Smart System was verified to give accurate and repeatable results over time.

Conclusion:

The information submitted in this premarket notification is complete and demonstrates that the modified BreathID® Hp Lab System, the BreathID® Smart System, is as safe and effective as the predicate device and supports a substantial equivalence decision.

Regulation Number and Section

§ 866.3110

Campylobacter fetus serological reagents.(a)
Identification. Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identifyCampylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases.Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.(b)
Classification. Class I (general controls).