(83 days)
The Exalenz BreathID® Hp System is intended for use to continually and non-invasively measure changes in the 1302 / 1202 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 System is indicated for use as an aid in the initial diagnosis and post treatment monitoring of H. pylori infection in adult patients. The Exalenz BreathID® Hp System consists of the IDkit:Hp™ and the BreathID® Hp test device.
The device is for use by trained health care professionals. To be administered under a physician's supervision.
The modified BreathID® Hp System is a non-invasive 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 the ratio between 1302 and 1202 concentrations in the patient's exhalation and a test kit. The test kit consists of:
- IDcircuit™ Oridion Nasal FilterLine™ (nasal cannula) (K980325)
- A 75mq 13C-urea tablet
- A 4.3g package of powdered Citrica (citric acid)
- Drinking straw
- Package Insert (Instructions for Use)
The modified BreathID® Hp System measures and computes the ratio between 1302 and 1202 in the patient's exhalation before and after the ingestion of 13C-urea. The change in the 1302 / 1202 ratio before and after ingestion of 13C-urea is referred to as the Delta over Baseline (DOB).
The basis of the 13C measurement method for both the modified versions of the BreathID® System is a technology called Molecular Correlation Spectroscopy™ (MCS™), MCS™ is based on the concept of optical absorption of specific radiation emitted from CO2 discharge lamps.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The core of the acceptance criteria for substantial equivalence in the clinical validation centered on the agreement between the modified BreathID® Hp System and its predicate device (unmodified BreathID® System) for H. pylori diagnosis.
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Positive Percent Agreement: ≥ 95% | 100% [95% Cl (81.6, 100)] |
| Negative Percent Agreement: ≥ 95% | 97% [95% Cl (89.0, 99.1)] |
| Comparative Validation (Analytical): | |
| Pearson's Correlation Coefficient (r) | r = 0.9944 (95% Cl: [0.9904, 0.9966]) |
| p-value | p < 0.0001 |
| Deming Slope [95% CI] | 1.06 [1.029, 1.095] |
| Deming Intercept [95% CI] | -0.05 [-0.302, 0.197] |
| Precision Validation (Analytical): | |
| Repeatability (DOB: 4.3‰) | 12.0% CV |
| Between-Days Precision (DOB: 4.3‰) | 12.9% CV |
| Repeatability (DOB: 5.9‰) | 8.2% CV |
| Between-Days Precision (DOB: 5.9‰) | 11.8% CV |
| Repeatability (DOB: 15.5‰) | 4.4% CV |
| Between-Days Precision (DOB: 15.5‰) | 4.7% CV |
| Reproducibility Validation (Analytical): | |
| Reproducibility (DOB: 4.5‰) | 10.9% CV |
| Between-Days Reproducibility (DOB: 4.5‰) | 11.0% CV |
| Between-Operators Reproducibility (DOB: 4.5‰) | 10.9% CV |
| Reproducibility (DOB: 5.9‰) | 9.2% CV |
| Between-Days Reproducibility (DOB: 5.9‰) | 10.6% CV |
| Between-Operators Reproducibility (DOB: 5.9‰) | 11.4% CV |
| Reproducibility (DOB: 15.5‰) | 3.4% CV |
| Between-Days Reproducibility (DOB: 15.5‰) | 3.4% CV |
| Between-Operators Reproducibility (DOB: 15.5‰) | 3.4% CV |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Test Set): 79 valid subjects (PP analysis set).
- Data Provenance: The document states "A single center, non-randomized, comparative study was conducted..." indicating it was a prospective study. The country of origin is not explicitly stated, but the applicant's address is in Modiin, Israel and the FDA letter indicates the submission date. There is also a reference to "Asian-Pacific" ethnicity, which could suggest a diverse study population, but does not explicitly state the location of the clinical trial.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The clinical study primarily focused on demonstrating equivalence between the modified device and the predicate device. The "ground truth" for H. pylori infection in the clinical study was established by "local clinical practice" and "serum blood tests". The document mentions that if a serum blood test was performed, "these blood tests were the only means used to diagnose the presence of H. pylori." No specific number or qualifications of experts involved in interpreting these blood tests or overall clinical diagnosis are provided.
4. Adjudication Method for the Test Set
The document does not describe a formal adjudication method (like 2+1 or 3+1) for establishing the ground truth diagnoses. The diagnosis was based on standard clinical practice, primarily serum blood tests where performed. The breath tests (both modified and unmodified) were "masked from the treating physician and did not have an impact on the patient's treatment," implying that the ground truth was independently established.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not explicitly described. The study compared the performance of two devices (modified vs. unmodified BreathID® System) rather than human readers with and without AI assistance. The device itself is a measurement instrument, not an AI to assist human readers in image interpretation, for example.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
While the device provides an objective measurement (DOB), the clinical validation compares its diagnostic output to the predicate device, also a standalone diagnostic, and ultimately to clinical diagnoses. The device itself is "algorithm only" in the sense that it processes breath samples and outputs a DOB value without human interpretive assistance for that value. The clinical study was designed to show that this standalone capability of the modified device is equivalent to the predicate device's standalone capability.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, Etc.)
For the clinical validation, the ground truth for H. pylori infection was established through local clinical practice, primarily serum blood tests. In cases where no blood test was performed, patient follow-up and symptom progression were mentioned, but the primary reference for diagnosis was serum blood tests.
For the analytical studies (Comparative, Precision, Reproducibility Validations), the "ground truth" or reference was based on three H. pylori samples with known expected DOB values (high, low, and moderate positive), as defined by FDA Draft Guidance. This refers to controlled samples with established concentrations, not patient-derived clinical ground truth.
8. The Sample Size for the Training Set
The document does not explicitly mention a training set or its sample size. The submission focuses on demonstrating substantial equivalence of a modified device to a predicate, and therefore the described studies are primarily validation and verification tests. It's possible the original BreathID® System (K011668) had training data, but it is not discussed for this 510(k) submission.
9. How the Ground Truth for the Training Set Was Established
Since no explicit training set is mentioned, the method for establishing its ground truth is also not described.
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Exalenz Bioscience Ltd. – Traditional 510(k) – Modified BreathID® Hp System Section 7: 510(k) Summary
Section 7: 510(k) Summary
MAY 2 2 2013
Introduction:
This document contains the 510(k) Summary for the modified BreathID® Hp System. The content of this summary is based on the requirements of 21 CFR 807.92(c).
| Applicant / ManufacturerName and Address: | Exalenz Bioscience Ltd.4 Ha' Maayan St.Modiin, Israel 71700 | ||
|---|---|---|---|
| 510(k) Contact Person: | Clay AnselmoPresidentReglera LLC | ||
| Email: anselmoc@reglera.comPhone: (303) 223-4303Fax: (303) 832-6700 | |||
| Date Prepared: | February 27, 2013 | ||
| Device Name: | BreathID® Hp System | ||
| Classification: | Class I | ||
| Classification Name: | Campylobacter fetus serological agents | ||
| Regulation Number: | 21 CFR 866.3110 | ||
| Product Code: | MSQ |
Predicate Devices:
The modified BreathID® Hp System is claimed to be substantially equivalent to the following legally marketed predicate device:
BreathID® System, Exalenz Bioscience Ltd., K011668 트
General Description:
The modified BreathID® Hp System is a non-invasive 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 the ratio between 1302 and 1202 concentrations in the patient's exhalation and a test kit. The test kit consists of:
- IDcircuit™ Oridion Nasal FilterLine™ (nasal cannula) (K980325) ■
- . A 75mq 13C-urea tablet
- A 4.3g package of powdered Citrica (citric acid) l
- 트 Drinking straw
- . Package Insert (Instructions for Use)
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Exalenz Bioscience Ltd. - Traditional 510(k) - Modified BreathID® Hp System Section 7: 510(k) Summary
The modified BreathID® Hp System measures and computes the ratio between 1302 and 1202 in the patient's exhalation before and after the ingestion of 13C-urea. The change in the 1302 / 14002 ratio before and after ingestion of "C-urea is referred to as the Delta over Baseline (DOB).
The basis of the 13C measurement method for both the modified versions of the BreathID® System is a technology called Molecular Correlation Spectroscopy™ (MCS™), MCS™ is based on the concept of optical absorption of specific radiation emitted from CO2 discharge lamps.
Intended Use / Indications for Use:
The Exalenz BreathID® Hp System is intended for use to continually and non-invasively measure changes in the 1902 / 1202 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 System is indicated for use as an aid in the initial diagnosis and post treatment monitoring of H. pylori infection in adult patients. The Exalenz BreathID® Hp System consists of the IDkit:Hp™ and the BreathID® Hp test device.
The device is for use by trained health care professionals. To be administered under a physician's supervision.
Comparison of Technological Characteristics:
The key characteristics of the modified BreathID® Hp System are substantially equivalent to the prior cleared version of the device in all regards. Any differences are minor, are supported by testing, and do not raise new types of questions of substantial equivalence.
The modified Breath!D® Hp System has the same fundamental scientific technology and principle of operation utilized in the unmodified BreathID® System. The technological modifications of the BreathID® Hp System are modifications to the configuration of the system and software revisions as a result of the modified hardware configuration.
This modified BreathID® Hp System is designed to be more compact, less expensive and easier to maintain than the unmodified system. In addition, the modified BreathID® Hp System either eliminates or consolidates components that have become redundant or obsolete.
Comparison of Intended Use:
There are no significant changes in the intended use or the indications for use between the modified BreathID® Hp System and the unmodified BreathID® System. The use environment, target user, and patient population of the modified BreathlD® Hp System are the same as the unmodified device.
Substantial Equivalence:
The following tables summarize the similarities and differences of the Exalenz BreathID® System cleared in K011668 to the modified Exalenz BreathID® Hp System that is the subject of this 510(k) submission.
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{3}------------------------------------------------
Exalenz Bioscience Ltd. – Traditional 510(k) – Modified BreathID® Hp System
Section 7: 510(k) Summary
:
| Specification /Characteristic | Exalenz Modified BreathID® Hp System | Exalenz BreathID® System (K011668) |
|---|---|---|
| Test Meal | 4.3g Citrica (citric acid) dissolved in water | 4.3g Citrica (citric acid) dissolved in water |
| Test Duration | 10-30 minutes | 10-30 minutes |
| Breath Collection | Continually over test duration | Continually over test duration |
| Cut-off Point | 5.0 DOB per mil (post dose minus pre dose) | 5.0 DOB per mil (post dose minus pre dose) |
| Organism | Helicobacter pylori in vivo | Helicobacter pylori in vivo |
| Reagent | 13C Urea | 13C Urea |
| Result | 13CO2/12CO2 ratio – Molecular CorrelationSpectroscopy™ (MCS™) | 13CO2/12CO2 ratio – Molecular CorrelationSpectroscopy™ (MCS™) |
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Page 7-4 of 13
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nz Bioscience Ltd. – Traditional 510(k) – Modified BreathlD® H
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{5}------------------------------------------------
Exalenz Bioscience Ltd. - Traditional 510(k) - Modified BreathID® Hp System Section 7: 510(k) Summary
Discussion of Differences
All differences between the modified and unmodified versions of the device have been formally verified or validated to ensure that the changes do not impact device specifications or performance.
The device instructions for use have been updated to reflect the changes made to the operator / device interface and to incorporate the clinical performance characteristics of the device itself. The changes made do not alter the Indications / Contraindications or Warnings / Precautions.
The hardware / physical configuration has been modified in comparison to the unmodified BreathlD® System. As demonstrated by the results of verification and validation, the modified hardware / physical configuration of the modified BreathID® Hp System does not have an effect on performance or substantial equivalence as compared to the unmodified BreathID® System.
Software changes have been implemented for the modified BreathID® Hp System related to the modified hardware configuration of the device. The software changes do not affect the safety and effectiveness of the modified BreathID® Hp System as compared to the unmodified BreathID® System.
Summary of Performance Bench Testing
Exalenz has performed verification and validation bench testing for demonstration of substantial equivalence of the modified BreathID® Hp System to the unmodified BreathID® System. The following key verification and validation bench tests are the most significant for establishing substantial equivalence:
- · Gas Collection Verification
- . System Check Verification
- . Comparative Validation
- . Analytical Studies
- o Precision Validation
- Reproducibility Validation o
- Software Verification and Validation
A summary of the Gas Collection, System Check Verification, Software Verification and Validation, Comparative Validation, Precision Validation and Reproducibility Validation is provided below.
Gas Collection Verification
A Gas Collection Verification was performed to verify that the 1202 and 1302 measurement subsystem of the BreathID® Hp System could adequately replace the Capnograph of the unmodified BreathID® System for measuring the CO2 concentration in incoming gases. Twenty (20) tests were performed with breath samples that were not 130 enriched from ten (10) different Each of the twenty (20) tests also included seven (7) DOB measurements from the subiects. measurement phase (MP) in various calibration ranges. The results of the Gas Collection Verification demonstrated that the DOB standard deviation of all measurement phase (MP) test results were within the specifications, all MP test sample concentrations were within the calibration range, and that all MP sample concentrations had a standard deviation of less than 0.2. Therefore, the 1202 cell of the 1302 and 1202 measurement subsystem of the BreathID® Hp System has been verified to adequately replace the Capnograph of the unmodified BreathID® System for measuring the CO2 concentration in incoming gases.
System Check Verification
A System Check Verification was performed to verify that operator breath or pre-dose patient breath could adequately replace the gas canister containing approximately 100% CO2 for the purposes of the System Check, one of the Quality Control functions of the BreathID® Hp System and the unmodified BreathID® System. Twenty (20) tests were performed with breath samples from eleven (11) different subjects. Each of the twenty (20) tests also included seven (7) DOB measurements. The results of the System Check Verification demonstrated that in all cases where the 12C curves
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Exalenz Bioscience Ltd. - Traditional 510(k) - Modified BreathID® Hp System Section 7: 510{k} Summary
were randomly changed and a calibration was then required, the situation was correctly identified by the BreathID® Hp System and a calibration was performed. In all cases where the 14C curves were unchanged and the calibration process was unable to expand the calibration range, the BreathlD® Hp System correctly identified the situation and did not perform a calibration. In the case where the 12 curve was unchanged, but the calibration range was expanded and a calibration was then required the BreathID® Hp System correctly identified the situation and performed a calibration. All test results following a System Check and calibration were within the specifications of the Breath!D® Ho System. Additionally, all test results following a System Check that did not require calibration were within the specifications of the BreathID® Hp System. Therefore, the System Check Verification not only demonstrated that operator breath or pre-dose patient breath could be adequately used for the System Check procedure, but it also demonstrated that the calibration process was effective.
Software Verification and Validation
Software Verification evaluated all system functionality and consisted of evaluations of the software through unit integration and system level testing, as well as code reviews. Software Validation consisted of various test cases to qualitatively test the software system of the BreathID® Hp System. The test case categories that were utilized for the software validation of the BreathID® Hp System were:
- l H. Pylori Patient Mode Tests
- l System Test
- . Utilities, and
- 트 System Failures
All test cases were implemented with a known input and an expected output. The expected output was visually compared against the actual output. All test cases were verified to have passing results.
Comparative Validation
A Comparative Validation was performed to evaluate the agreement of the modified BreathID® Hp System DOB measurements to its predicate device, the unmodified BreathID® System. The Comparative Validation was performed in accordance with the following standard:
- Clinical and Laboratory Standards Institute EP09-A2 Method Comparison and Bias u Estimation Usina Patient Samples: Approved Guideline - Second Edition
The Comparative Validation was performed with three H. pylori samples that included a high positive, low positive and moderate positive, as defined in the FDA Draft Guidance "Establishing Performance Characteristics of In Vitro Diagnostic Devices for the Detection of Helicobacter pylori, September 23, 2010. The Comparative Validation was performed with one modified BreathID® Hp System and one unmodified BreathlD® System, executing two runs per day for five days. Each test run included three different combinations of baseline / post-ingestion gases and each combination of baseline / post-ingestion gases was consecutively tested twice. The modified BreathlO® Hp System and the unmodified BreathID® System were evaluated simultaneously by connecting the two devices with a Y-Connector. Calibration was performed on the first day of the Comparative Validation. Table 7-3 below provides the results and analysis of the Comparative Validation.
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| ExpectedDOB | Parameter | N | Mean | SD | Min | Median | Max |
|---|---|---|---|---|---|---|---|
| DOB:4.5‰ | DOBModifiedBreathID® | 20 | 4.96 | 0.350 | 4.3 | 4.97 | 5.6 |
| DOBUnmodifiedBreathID® | 20 | 4.69 | 0.233 | 4.2 | 4.65 | 5.2 | |
| Differencein DOBBetweenDevices | 0.27 | 0.368 | -0.5 | 0.28 | 1.0 | ||
| DOB:5.8‰ | DOBModifiedBreathID® | 20 | 6.37 | 0.297 | 6.0 | 6.33 | 7.0 |
| DOBUnmodifiedBreathID® | 20 | 6.07 | 0.266 | 5.5 | 6.07 | 6.5 | |
| Differencein DOBBetweenDevices | 0.30 | 0.366 | -0.3 | 0.20 | 0.9 | ||
| DOB:13‰ | DOBModifiedBreathID® | 20 | 14.09 | 0.424 | 13.2 | 14.03 | 14.9 |
| DOBUnmodifiedBreathID® | 20 | 13.32 | 0.358 | 12.4 | 13.37 | 13.8 | |
| Differencein DOBBetweenDevices | 0.78 | 0.526 | -0.3 | 0.75 | 1.7 |
| Table 7-3: Distribution of DOB Measurements Between Modified and Unmodified BreathlD® Systems | |||
|---|---|---|---|
A Pearson's correlation coefficient was calculated between the DOB measurements from the unmodified and modified BreathID® Systems. A correlation plot of the DOB measurements from the modified and unmodified BreathID® Systems is provided in Figure 7-1 below. The following values were calculated:
l r = 0.9944 (95% Cl: [0.9904, 0.9966]
I p < 0.0001
{8}------------------------------------------------
Image /page/8/Figure/0 description: The image is a scatter plot titled "Modified BreathID vs. BreathID". The x-axis is labeled "DOB Modified BreathID", and the y-axis is labeled "DOB BreathID". The plot shows a strong positive correlation between the two variables, with a correlation coefficient of 0.99 and a p-value of less than 0.0001. There is also a line of equality shown on the plot.
Exalenz Bioscience Ltd. - Traditional 510(k) - Modified BreathID® Hp System Section 7: 510(k) Summary
Figure 7-1: Correlation Plot of DOB Measurements from Unmodified and Modified BreathlD® Systems
Table 7-4 below presents the slope and intercept of the Deming Regression, along with the respective 95% confidence interval (CI).
Table 7-4: Deming Regression Slope and Intercept
| Deming Slope [95% CI] | Deming Intercept [95% CI] |
|---|---|
| 1.06 [1.029, 1.095] | -0.05 [-0.302, 0.197] |
Precision Validation
The Precision Validation was performed in accordance with the following standards:
- Clinical and Laboratory Standards Institute EP05-A2 Evaluation of Precision Performance of . Quantitative Measurement Methods: Approved Guideline - Second Edition, 2004
- Clinical and Laboratory Standards Institute EP15-A2 User Verification of Performance for . Precision and Trueness; Approved Guideline - Second Edition, 2005
The Precision Validation was performed with three H. pylori samples that included a high positive, low positive and moderate positive, as defined in the FDA Draft Guidance "Establishing Performance Characteristics of In Vitro Diagnostic Devices for the Detection of Helicobacter pylori," September 23, 2010. The Precision Validation was performed using one modified BreathID® Hp System for twelve days, executing two runs per day. Each test run included three different combinations of baseline / post-ingestion combinations, and each combination of baseline / post-ingestion gases was consecutively tested twice. Calibration was performed on the first and seventh days of the Precision Validation. The tabulated accuracy results and the tabulated repeatability results are provided in Tables 7-5 and 7-6 below, respectively.
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| Expected DOB | Accuracy (Mean) | 95% CI |
|---|---|---|
| DOB: 4.3‰ | 4.67 | [4.5 - 4.85] |
| DOB: 5.9‰ | 5.85 | [5.52 - 6.17] |
| DOB: 15.5‰ | 15.78 | [15.57 - 15.99] |
Table 7-5: Precision Validation DOB Accuracy Results
Table 7-6: DOB Repeatability and Between-Day Precision
| Expected DOB | Parameter | SD Value | 95% CI | CV |
|---|---|---|---|---|
| DOB: 4.3‰ | Repeatability | 0.559 | [0.499 - 0.635] | 12.0% |
| Between-DaysPrecision | 0.603 | [0.525 - 0.681] | 12.9% | |
| DOB: 5.9‰ | Repeatability | 0.479 | [0.427 - 0.544] | 8.2% |
| Between-DaysPrecision | 0.691 | [0.621 - 0.760] | 11.8% | |
| DOB: 15.5‰ | Repeatability | 0.689 | [0.615 - 0.784] | 4.4% |
| Between DaysPrecision | 0.738 | [0.664 - 0.811] | 4.7% |
Reproducibility Validation
The Reproducibility Validation was performed in accordance with the following standards:
- Clinical and Laboratory Standards Institute EP05-A2 Evaluation of Precision Performance of ■ Quantitative Measurement Methods; Approved Guideline - Second Edition, 2004
- l Clinical and Laboratory Standards Institute EP15-A2 User Verification of Performance for Precision and Trueness; Approved Guideline - Second Edition, 2005
The Reproducibility Validation was performed with three H. pylori samples that included a high positive, low positive and moderate positive, as defined in the FDA Draft Guidance "Establishing Performance Characteristics of In Vitro Diagnostic Devices for the Detection of Helicobacter pylori," September 23, 2010. The Reproducibility Validation was performed using three devices in three different sites for five days. Two test runs were executed per day by different operators. Each test run utilized three different combinations of baseline / post-ingestion gases and each combination of baseline / post-ingestion gases was consecutively tested three times. Calibration was performed on the first day of the Reproducibility Validation. The tabulated accuracy results and the tabulated reproducibility results are provided in Tables 7-7 and 7-8 below, respectively.
| Expected DOB | Accuracy (Mean) | 95% Cl |
|---|---|---|
| റ്റാB: 4.5% | 00ﺎ ﺍﻟﻤﺮﺍﺟﻊ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍ | |
| റ്റാB: 5.9%ം | A Cে | |
| DOB: 15.5%0 | 15.69 |
Table 7-7: Reproducibility Validation DOB Accuracy Results
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| Expected DOB | Parameter | SD Value | 95% CI | CV |
|---|---|---|---|---|
| DOB: 4.5‰ | Reproducibility | 0.524 | 0.483 - 0.573 | 10.9% |
| Between-DaysReproducibility | 0.533 | 0.455 - 0.624 | 11.0% | |
| Between-OperatorsReproducibility | 0.524 | 0.444 - 0.619 | 10.9% | |
| DOB: 5.9‰ | Reproducibility | 0.563 | 0.518 - 0.615 | 9.2% |
| Between-DaysReproducibility | 0.648 | 0.576 - 0.712 | 10.6% | |
| Between-OperatorsReproducibility | 0.697 | 0.612 - 0.780 | 11.4% | |
| DOB: 15.5‰ | Reproducibility | 0.536 | 0.494 - 0.586 | 3.4% |
| Between-DaysReproducibility | 0.536 | 0.479 - 0.585 | 3.4% | |
| Between-OperatorsReproducibility | 0.538 | 0.485 - 0.591 | 3.4% |
| Table 7-8: DOB Reproducibility, Between-Day Reproducibility and Between-Operator Reproducibility | |||||
|---|---|---|---|---|---|
| -- | -------------------------------------------------------------------------------------------------- | -- | -- | -- | -- |
Summary of Clinical Validation
Exalenz conducted a clinical validation to demonstrate that the modified BreathlD® Hp System is substantially equivalent to the unmodified Breath1D® System.
A single center, non-randomized, comparative study was conducted to compare the modified BreathID® Hp System to the unmodified BreathID® System. The breath test was performed according to the standard procedure described in the device's instructions for use and routine clinical practice while the subject was connected simultaneously to both the Breath!D® Hp System and the unmodified BreathID® device via two standard nasal cannulae. The outcome measures of both devices were used for the comparison.
In order to prevent a spectrum bias, the breath test was performed in addition to, and independent of the local clinical practice. In cases were a serum blood test was performed, these blood tests were the only means used to diagnose the presence of H. pylori. In other cases, where the investigator did not feel a blood test was warranted (change in diet prescribed, or symptoms not specific to H. pylori), the patient was periodically followed up at the clinic as routine general practice with no eradication therapy prescribed. In these cases, only if symptoms persisted or became more related to H. pylori infection, was the patient sent for blood tests. The breath testing was performed by a site technician and not in the proximity of the Principal Investigator. The breath test results were made available to the treating physician (Principal Investigator) only once the patient's management protocol had been determined. Thus, the test results from both devices were masked from the treating physician and did not have an impact on the patient's treatment.
The clinical study was conducted in compliance with its protocol and in accordance with the ethical principles under Investigational Review Board (IRB) approval consistent with Good Clinical Practice (GCP) and with applicable regulatory requirements. Table 7-9 below presents the subjects' accountability and the subjects' baseline characteristics per protocol (PP).
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| Parameter | Statistic | PP |
|---|---|---|
| Age | N | 79 |
| Mean (SD) | 49.2 (16.54) | |
| Median [min-max] | 50.5 [18.4 - 87.8] | |
| Height | N | 77 |
| Mean (SD) | 164.0 (9.90) | |
| Median [min-max] | 163.0 [142.0 - 185.0] | |
| Weight | N | 79 |
| Mean (SD) | 69.5 (16.65) | |
| Median [min-max] | 66.0 [43.0 - 117.0] | |
| BMI | N | 77 |
| Mean (SD) | 25.7 (4.92) | |
| Median [min-max] | 24.4 [17.4 - 44.4] | |
| Sex | Male% (n/N) | 41.77% (33/79) |
| Female% (n/N) | 58.23% (46/79) | |
| Ethnicity | African-American% (n/N) | 1.27% (1/79) |
| Asian-Pacific% (n/N) | 68.35% (54/79) | |
| Caucasian% (n/N) | 12.66% (10/79) | |
| Hispanic% (n/N) | 15.19% (12/79) | |
| Other% (n/N) | 2.53% (2/79) |
Table 7-9: Subject Baseline Characteristics
PP Analysis Set
The PP analysis set consisted of all subjects enrolled in the study that did not have any major protocol deviations and had no other relevant H. pylori testing prior to enrollment in the study, which was defined as no positive test results within 2012 and no negative test results within three months prior to enrollment. The cross tabulation of the diagnosis as assessed by both the modified and unmodified BreathID® Systems in the PP analysis set is provided in Table 7-10 below. The PP analysis set included 79 valid subjects per the protocol.
Table 7-10: PP Analysis Set Agreement
| Unmodified BreathID® System | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| BreathID® HpSystem | Positive | 17 | 2 | 19 |
| Negative | --- | 60 | 60 | |
| Total | 17 | 62 | 79 |
Positive percent agreement = 100% * 17/17 = 100% [95% Cl (81.6, 100)] .
Negative percent agreement = 100% * 60/62 = 97% [95% Cl (89.0, 99.1)] .
These results satisfied the acceptance criterion of ≥ 95% and therefore the study was successful in demonstrating equivalence of the two devices.
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Conclusion
The modified Exalenz BreathID® Hp System is substantially equivalent with respect to the indications for use, intended use, use environment, target users, patient population, technological characteristics, and performance characteristics to the following legally marketed predicate device, K011668 - BreathID® System, Exalenz Bioscience Ltd.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/13/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal features the department's name arranged in a circular pattern around a central emblem. The emblem consists of a stylized caduceus, a symbol often associated with medicine and healthcare, with three intertwined snakes and a staff.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 22, 2013
Exalenz Bioscience Ltd. c/o Clay Anselmo President 11925 W 1-70 Frontage Rd, North Suite 900 Wheat Ridge, CO 80033
Re: K130524
Trade/Device Name: BreathID Hp System Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus serological reagents Regulatory Class: I Product Code: MSQ Dated: February 27, 2013 Received: February 28, 2013
Dear Mr. Anselmo:
We have reviewed your Section 510(k) premarket notification of intent to market the device wo nave 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). and Oosmeter rever . res) the device, subject to the general controls provisions of the Act. The r ou may, dicrerere, maints of the Act include requirements for annual registration, listing of general control pro resuring 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 your de rise is trabbitional controls. Existing major regulations affecting your device can be it may be subject to additions, Title 21, Parts 800 to 898. In addition, FDA may round in urther announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean I hat FDA has made a determination that your device complies with other requirements of the Act that I Dr has Intatutes and regulations administered by other Federal agencies. You must or any I oderal statutes and sequirements, including, but not limited to: registration and listing (21 Comply with an the rice of equitements, 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements miculude ree realited ad vester of (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer 607); prease commer the Driviner of 001638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part the regulation one the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the I ou may oounn other gefiners, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Sally 刷创ojvat -S
Sally Hojvat, Ph.D., M.Sc. Director, Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use Form
510(k) Number (if known): _ K130524
Device Name: BreathID® Hp System
Indications for Use:
The Exalenz BreathID® Hp System is intended for use to continually and non-invasively measure
changes in the 1302 / 1°CO2 ratio of exhaled breath, which may be indicative of production associated with active Helicobacter pylori infection in the stomach. The Exalenz 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. The Exalenz BreathID® Hp System consists of the IDkit:Hp™ and the BreathID® Hp test device.
The device is for use by trained health care professionals. To be administered under a physician's supervision.
AND/OR Over-The-Counter Use Prescription Use __ X (21 CFR 801 Subpart C) (Part 21 CFR 801 Subpart D)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Raquel A. Peat -S 2013.05.16 16:54:24 -04'00'
Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
K130524 510(k)_
§ 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).