The BreathID® Hp System is intended for use to continually and 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 BreathID® Hp 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 BreathID® Hp System consists of the appropriate IDkit Hp® kit and the BreathID® Hp test device.

The device is for use by trained health care professionals. To be administered under a physician's supervision.

Device Description

The BreathID® Hp System is a non-invasive breath test system for detecting the presence of Helicobacter pylori (H. pylori). The systems consist of an electro-optical medical device designed to measure and compute the changes in the ratio between 1302 and 1202 concentrations in the patient's exhalation, software, and a test kit.

The IDkit Hp® One test kit consists of:

. One Package Insert
One Tablet of 13C-enriched urea,75mg .
One packet of 4.3g of Powder Citrica (citric acid). .
One IDcircuit™ nasal cannula ●
. One straw for stirring and drinking

Using a nasal cannula for breath collection directly from the patient's nostrils enables point of care testing. The BreathID® Hp continually 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 "3C-urea is used to compute the Delta over Baseline (DOB).

The 13C measurement method 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

This document is a Special 510(k) submission for a labeling modification to an already cleared medical device, the BreathID® Hp System. A Special 510(k) is used when a modification to a cleared device does not affect its intended use, fundamental scientific technology, or safety/effectiveness profiles. This means the core performance characteristics of the device itself are not being re-evaluated in this submission, but rather the interpretation and communication of its results under specific circumstances (patients on PPIs).

Therefore, the submission does not contain information about the original acceptance criteria and the study that proved the device met those criteria. It focuses solely on the rationale for the labeling change.

Here's what can be extracted from the document:

1. Context of the Submission:

Trade/Device Name: BreathID® Hp System
Regulation Number: 21 CFR 866.3110 (Campylobacter Fetus Serological Reagents - note: this seems like a misclassification in the document for an H. pylori urea breath test, as H. pylori is a specific bacterial infection, not related to Campylobacter Fetus. This might be a generic regulation listed or an artifact. The actual product code aligns with urea breath tests.)
Regulation Name: Test, urea (breath or blood)
Regulatory Class: Class I, reserved
Product Code: MSQ, JJQ
Predicate Device: BreathID® Hp System (K173772)
Purpose of this 510(k): To obtain marketing clearance for a labeling modification of the BreathID® Hp System (K173772). This modification is solely to the package insert which is included in the IDkit Hp® One, the test kit used as part of this cleared 510(k) device, while the Intended Use and Indication for Use remain unchanged. The modified labeling informs clinicians that for patients taking proton pump inhibitors (PPIs), a positive result could be considered as indicative of the presence of urease enzyme associated with H. pylori.

2. What is Unchanged from the Cleared Device (K173772):

Intended Use / Indication for Use: "The BreathID® Hp System is intended for use to continually and 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 BreathID® Hp 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 BreathID® Hp System consists of the appropriate IDkit Hp® kit and the BreathID® Hp test device. The device is for use by trained health care professionals. To be administered under a physician's supervision."
Device Description: The system consists of an electro-optical medical device designed to measure and compute changes in the 13CO2 and 12CO2 ratio, software, and a test kit (IDkit Hp® One).
Measurement Method: 13C measurement based on Molecular Correlation Spectroscopy™ (MCS) technology.
Test Kit and Ingested Drug: The IDkit Hp® One test kit (13C urea tablet and citric acid powder approved in NDA-21-314), the procedure for ingestion of test substrate, and the breath collection method remain unchanged.
Technological Characteristics: Remain unchanged.
Performance Testing: "Performance characteristics remain unchanged." This explicitly states that no new performance testing (like sensitivity/specificity studies) was conducted for this submission because the underlying technology and operation are identical.

3. What is Changed (Labeling Modification):

The modification addresses the interpretation of results for patients using Proton Pump Inhibitors (PPIs), which were previously a known cause of false negative results. The new labeling clarifies that:

Old Warning Removed: "Antimicrobials, proton pump inhibitors, and bismuth preparations are known to suppress H. pylori. Ingesting these medications within two weeks prior to performing the breath test mav produce false negative test results."
New Statements Added/Revised:
- False negative results may still be caused by PPIs within two weeks prior to testing.
- If a negative result is obtained from a patient ingesting a PPI within two weeks, it may be a false-negative and the test should be repeated two weeks after discontinuing PPIs.
- Crucially: "A positive result for a patient on a PPI could be considered as indicative of the presence of urease associated with H. pylori." (This is the core change, allowing interpretation of positive results even with PPI use, whereas previously any use of PPIs within the window could make results unreliable).

Addressing your specific questions based on the provided text:

Since this is a Special 510(k) for a labeling change on a previously cleared device, the document does not contain the details of the original performance studies. The submission explicitly states "Performance characteristics remain unchanged," indicating no new studies were performed to demonstrate that the device meets new acceptance criteria. Instead, it reinterprets existing performance for a specific clinical scenario.

Therefore, most of your questions cannot be answered from this specific document.

Here's what can be inferred or directly stated, and what cannot:

A table of acceptance criteria and the reported device performance:
- Cannot be provided from this document. This information would be in the original 510(k) submission for K173772. This current document states that performance characteristics remain unchanged, meaning the device still meets the original acceptance criteria.
Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- Cannot be provided from this document. This would be in the original K173772 submission. No new clinical studies were conducted for this labeling change.
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):
- Cannot be provided from this document. This would be in the original K173772 submission.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Cannot be provided from this document. This would be in the original K173772 submission.
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:
- Not applicable. This device is a diagnostic test (urea breath test, non-imaging) and does not involve "human readers" or "AI assistance" in the typical sense of imaging analysis for which MRMC studies are performed. Its output is interpretable directly as positive or negative based on the device's measurement.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Partially applicable/inferred. For a diagnostic test like this, the device itself provides the measurement. The "standalone" performance would be its sensitivity and specificity against a "true" H. pylori status. This data would have been part of the original K173772 clearance. The current submission implies that the device's measurement capabilities remain the same.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Cannot be provided from this document but can be inferred. For H. pylori breath tests, the ground truth is typically established by other diagnostic methods for H. pylori, such as biopsy with histology, rapid urease test (RUT), or culture, or a combination (composite reference standard). This information would be in the original K173772 submission.
The sample size for the training set:
- Not applicable. This product is a diagnostic device, not an AI/ML algorithm that requires a "training set" in the computational sense. The device's parameters are likely calibrated and validated, but not "trained" on data in the same way.
How the ground truth for the training set was established:
- Not applicable. See point 8.

In summary, this document is an administrative update for a minor change in labeling interpretation, not a re-clearance or new performance study for the device itself. To get the requested information about device performance and the original studies, one would need to access the original 510(k) submission document (K173772).

Summary

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December 19, 2022

Meridian Bioscience Israel Ltd. Raffi Werner VP Meridian Bioscience Israel 4 Ha'Maayan St Modiin, 7177872 Israel

Re: K221896

Trade/Device Name: BreathID Hp System Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter Fetus Serological Reagents Regulatory Class: Class I, reserved Product Code: MSQ, JJQ Dated: June 28, 2022 Received: June 30, 2022

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.

Please note that if you modify your IVD in the future to exceed any of the limitations to the exemption found in 21 CFR 866.9(c), your device will require a new 510(k) prior to marketing this device in the United States and will not be exempt from the premarket notification requirements so long as it exceeds the limitations to the exemption found in 21 CFR 866.9.

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.

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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 803) 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 -S

Ribhi Shawar, Ph.D. (ABMM) Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics 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) K221896

Device Name BreathID® Hp System

Indications for Use (Describe)

The device is for use by trained health care professionals. To be administered under a physician's supervision.

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

X 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 purpose of this Special 510(k) submission is to obtain marketing clearance for a labeling modification of the BreathID® Hp System (K173772). This labeling modification is solely to the package insert which is included in the IDkit Hp® One, the test kit used as part of this cleared 510(k) device, while the Intended Use and Indication for Use remain unchanged. The modified labeling informs clinicians that for patients taking proton pump inhibitors (PPIs), a positive result could be considered as indicative of the presence of urease enzyme associated with H. pylori. PPIs are a family of prescription and over-the-counter drugs that help alleviate the symptoms caused by H. pylori infection.

Applicant's Name

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

Contact Person

Raffi Werner Meridian Bioscience Israel Ltd. 4 Ha'Maayan Street Modiin, 7177872, Israel Tel: +972-8-9737502 Fax: +972-8-9737501 Raffi.werner@meridianbioscience.com

Date Prepared

June 28, 2022

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Trade Name

BreathID® Hp System

Classification Name

Test, urea (breath or blood)

Product Code

MSQ, JJQ

Device Class

Regulation Number

866.3110

Panel

Microbiology

Predicate Device

BreathID® Hp System [Meridian Bioscience Israel Ltd.] cleared under K173772.

Device Description (unchanged from cleared device)

The IDkit Hp® One test kit consists of:

. One Package Insert
One Tablet of 13C-enriched urea,75mg .
One packet of 4.3g of Powder Citrica (citric acid). .
One IDcircuit™ nasal cannula ●
. One straw for stirring and drinking

Using a nasal cannula for breath collection directly from the patient's nostrils enables point of care testing. The BreathID® Hp continually measures and computes the ratio between 13CO2 and 12CO2

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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 "3C-urea is used to compute the Delta over Baseline (DOB).

Intended Use / Indication for Use (unchanged from cleared device)

The BreathID® Hp System is intended for use for continually and non-invasively measure changes in the '3CO2/12CO2 ratio of exhaled breath, which may be indicative of increased urease production associated with active Helicobacter pylori (H. pylori) infection in the stomach.

Substantial Equivalence

The device and kit of the BreathID® Hp System that is subject of this Special 510(k) labeling modification request is identical to the device and kit of the cleared predicate BreathID® Hp System (K173772). The exact same technology and the same principles of operation are used, including the same test kit, utilizing the same test substrate and same method to collect patient's exhaled breath samples for the test, as the predicate device.

The labeling modification in this submission is specifically related to the current limitation for those patients taking proton pump inhibitors (PPIs) and performing the breath test and is reflected in changes to the package insert of the test kit, IDkit Hp® One that is used as part of the BreathID® Hp System. This labeling modification informs clinicians that a positive result could be considered as indicative of the presence of urease enzyme associated with H. pylori in patients using PPIs, a family of prescription and over-the-counter drugs that helps alleviate the symptoms caused by H. pylori infection. The changes in the Package Insert are described below:

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1. In Section 5.2 Warnings and Precautions, item 7 is revised to remove the following statement:
  "Antimicrobials, proton pump inhibitors, and bismuth preparations are known to suppress H. pylori. Ingesting these medications within two weeks prior to performing the breath test mav produce false negative test results."

The following statements will replace the removed warning:

"False negative test results may be caused by:

Ingestion of antimicrobials or bismuth preparations within two weeks prior to performing . the breath test.
. Ingestion of proton pump inhibitors (PPIs) within two weeks prior to performing the breath test.

Note: If a negative result is obtained from a patient ingesting a PPI within two weeks prior to the breath test, it may be a false-negative result and the test should be repeated two weeks after discontinuing the PPI treatment. A positive result for a patient on a PPI could be considered as indicative of the presence of urease associated with H. pylori."

1. In Section 7.7 Operational Precautions and Limitations, item 4-6 is revised to accept positive breath test results in patients using PPIs as is in the following statement:

"The patient should not have taken antimicrobials, proton pump inhibitors (PPI) or bismuth preparations within two weeks prior to administering the breath test.
If the test is negative and it is determined that the subject has used PPIs within two weeks prior to taking the breath test, the test may provide a false negative result. The test needs to be repeated in two weeks post discontinuation of PPI treatment.
A positive result for a patient on PPI could be considered as indicative of the presence of urease enzyme associated with H. pylori.

Note: The numbering of the next items in this section was adjusted accordingly.

1. Section 8.1 Patient Preparation is revised to accept positive breath test results in patients using PPIs as in the following statement:
  "The patient should have fasted at least one hour before administering the solution. The patient should not have taken antimicrobials, proton pump inhibitors (PPI) or bismuth preparations within two weeks prior to administering the test. If PPIs are used within two weeks of breath testing, false negative test results may occur, and the test should be repeated two weeks after discontinuation of PPI treatment. A positive result for a patient on PPI could be considered as indicative of the presence of urease enzyme associated with H. pylori."

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Test Kit and Ingested Drug

The IDkit Hp® One test kit that includes the 13C urea tablet and citric acid powder approved in NDA-21-314, the procedure for ingestion of test substrate, and the breath collection method remain unchanged.

Comparison of Technological Characteristics

Technological characteristics remain unchanged.

Summary of Performance Testing

Performance characteristics remain unchanged.

Conclusion:

The information submitted in this premarket notification is complete and supports a finding of substantial equivalence.

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).