BreathID Hp Lab System
Device Facts
| Record ID | K162150 |
|---|---|
| Device Name | BreathID Hp Lab System |
| Applicant | Exalenz Bioscience , Ltd. |
| Product Code | MSQ · Microbiology |
| Decision Date | Oct 31, 2016 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3110 |
| Device Class | Class 1 |
Indications for Use
The Exalenz BreathID® Hp Lab 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 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 Lab System consists of the IDkit:Hp™ kits, and the BreathID® Hp device, Auto Sampler and Lab Application. To be administered by trained personnel as ordered by a licensed healthcare practitioner.
Device Story
System measures 13CO2/12CO2 ratio in human breath to detect H. pylori-associated urease activity. Patient ingests 13C-urea tablet with citric acid; breath samples collected in two bags (baseline and post-ingestion). Auto Sampler processes bags sequentially; BreathID® Hp device uses Molecular Correlation Spectroscopy (MCS) to measure infrared light absorbance, correlating to CO2 concentrations. System computes Delta Over Baseline (DOB) and provides positive/negative determination. Used in clinical/lab settings by trained personnel; results assist physicians in diagnosis and monitoring. Benefits include non-invasive testing and ability to perform off-site/deferred batch analysis.
Clinical Evidence
Pivotal multi-center study (189 initial diagnosis, 68 post-therapy patients) compared BreathID Hp Lab System to composite reference (histology and RUT). Pre-therapy: 100% sensitivity, 97.9% specificity. Post-therapy: 92.3% sensitivity, 100% specificity. Stability study (n=191) confirmed 14-day sample bag storage reliability with 97.8% positive agreement and 100% negative agreement.
Technological Characteristics
Molecular Correlation Spectroscopy (MCS) using infrared spectrometry; CO2 discharge lamps. Components: BreathID® Hp analyzer, Auto Sampler, Lab Application, IDkit:Hp™ Two (13C-urea tablet, citric acid). Connectivity: Workstation-based. Software: Embedded firmware in analyzer and Auto Sampler. Dimensions/Materials: Not specified.
Indications for Use
Indicated for initial diagnosis and post-treatment monitoring of active Helicobacter pylori (H. pylori) infection in adult patients.
Regulatory Classification
Identification
Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identify Campylobacter 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.
Predicate Devices
- Exalenz BreathID® Hp System (K130524)
Related Devices
- K173772 — BreathID Hp System · Exalenz Bioscience , Ltd. · Mar 8, 2018
- K173777 — BreathID Hp Lab System · Exalenz Bioscience , Ltd. · Mar 8, 2018
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE
A. 510(k) Number:
K162150
B. Purpose for Submission:
Clearance of the BreathID® Hp lab System with the IDkit Hp Two test kit
C. Measurand:
Changes in the $^{13}\mathrm{CO}_2/^{12}\mathrm{CO}_2$ ratio of exhaled breath following ingestion of $^{13}\mathrm{C}$ urea
D. Type of Test:
H. pylori $^{13}\mathrm{C}$-Urea Breath Test
E. Applicant:
Exalenz Bioscience Ltd.
F. Proprietary and Established Names:
BreathID® Hp Lab System
G. Regulatory Information:
1. Regulation section:
866.3110 Campylobacter fetus serological reagents
2. Classification:
Class I
3. Product code:
MSQ, JJQ
4. Panel:
83 Microbiology
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H. Intended Use:
1. Intended use(s):
The Exalenz BreathID® Hp Lab System is intended for use to non-invasively measure changes in the $^{13}\mathrm{CO}_2/^{12}\mathrm{CO}_2$ 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 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 Lab System consists of the IDkit:Hp™ kits, and the BreathID® Hp device, Auto Sampler and Lab Application.
To be administered by trained personnel as ordered by a licensed healthcare practitioner.
2. Indication(s) for use:
The Exalenz BreathID® Hp Lab System is intended for use to non-invasively measure changes in the $^{13}\mathrm{CO}_2/^{12}\mathrm{CO}_2$ 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 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 Lab System consists of the IDkit:Hp™ kits, and the BreathID® Hp device, Auto Sampler and Lab Application.
To be administered by trained personnel as ordered by a licensed healthcare practitioner.
3. Special conditions for use statement(s):
Prescription use only
4. Special instrument requirements:
For use with the Exalenz BreathID Hp Lab System
I. Device Description:
The BreathID® Hp Lab 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 ratio between $^{13}\mathrm{CO}_2$ and $^{12}\mathrm{CO}_2$ concentrations in the patient's exhalation.
The IDkit Hp™ Two test kit consists of:
- One (1) baseline breath sample bag
- One (1) post-ingestion breath sample bag
- One (1) large sample transport bag
- A 75mg $^{13}$C-urea tablet
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A $4.3\mathrm{g}$ package of powdered Citrica (citric acid)
Drinking straw
IDkit $\mathrm{Hp}^{\mathrm{TM}}$ Two Package Insert (Instructions for Use)
The BreathID® Hp Lab System measures and computes the ratio between $^{13}\mathrm{CO}_2$ and $^{12}\mathrm{CO}_2$ in the patient's exhalation before and after the ingestion of $^{13}\mathrm{C}$ -urea. The change in the $^{13}\mathrm{CO}_2 / ^{12}\mathrm{CO}_2$ ratio before and after ingestion of $^{13}\mathrm{C}$ -urea is referred to as the Delta over Baseline (DOB).
The $^{13}\mathrm{C}$ measurement method for the BreathID® Hp systems is based on Molecular Correlation Spectroscopy™ (MCS) technology. MCS technology is based on the concept of optical absorption of specific radiation emitted from $\mathrm{CO}_{2}$ discharge lamps.
# J. Substantial Equivalence Information:
1. Predicate device name(s): Exalenz BreathID Hp System
2. Predicate 510(k) number(s): K130524
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device BreathID® Hp Lab System | Predicate BreathID® Hp System (K130524) |
| Intended Use | The Exalenz BreathID® Hp Lab 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 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 Lab System consists of the IDkit:HpTM kits, and the BreathID® Hp device, Auto Sampler and Lab Application. To be administered by trained | The Exalenz 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 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:HpTM and the BreathID® Hp test device. The device is for use by trained |
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| Similarities | | |
| --- | --- | --- |
| Item | Device BreathID® Hp Lab System | Predicate BreathID® Hp System (K130524) |
| | personnel as ordered by a licensed healthcare practitioner. | health care professionals. To be administered under a physician's supervision. |
| Indications | Initial diagnosis and post treatment monitoring | Same |
| Organism | Helicobacter pylori | Same |
| Reagent | \( ^{13}\mathrm{C} \) Urea (NDA 21-314) | Same |
| Detection Method | Measuring levels of \( ^{13}\mathrm{CO}_{2} \) and \( ^{12}\mathrm{CO}_{2} \) using Molecular Correlation Spectroscopy (MCS) | Same |
| Test Output (Reported Result) | Delta Over Baseline (DOB) of the \( ^{13}\mathrm{CO}_{2}/^{12}\mathrm{CO}_{2} \) ratio (before and after ingestion of \( ^{13}\mathrm{C} \) Urea) and positive/negative determination for H. pylori infection | Same |
| Cut-off Point | 5.0 DOB per mil (post dose minus pre dose) | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device BreathID® Hp Lab System | Predicate BreathID® Hp System (K130524) |
| Test Sample | Human breath exhaled into breath sample bags | Human breath collected using a nasal cannula |
| Sample Collection Method | Two breath sample bags: for baseline and for post ingestion | Continual collection over the test duration through a nasal cannula |
| Test Duration | 15-20 minutes | 10-30 minutes |
| System Hardware Components | • BreathID® Hp Lab Application with Work Station • Auto Sampler • IDkit:Hp™ Two test kit | • BreathID® Hp device • IDkit:Hp™ One test kit |
| System Software Components | • BreathID® Hp Lab device embedded software • BreathID® Hp Lab Application • Auto Sampler embedded software | BreathID® Hp device embedded software |
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K. Standard/Guidance Document Referenced:
CLSI EP05-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition
CLSI EP09-A3 Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition
CLSI EP15-A2 User Verification of Performance for Precision and Trueness; Approved Guideline – Second Edition
IEC 60601-1-2 Medical Electrical Equipment Part 1-2: General Requirements for Basic Safety and Essential Performance – Collateral Standard: Electromagnetic Compatibility – Requirements and Tests
EN 60601-1 Medical Electrical Equipment Part 1: General Requirements for Basic Safety and Essential Performance
IEC 62304 Medical Device Software – Software Life Cycle Processes
EN ISO 14971 Medical Devices – Application of Risk Management to Medical Devices
ISO 10993-1 Biological Evaluation of Medical Devices Part 1: Evaluation and Testing
ISO 13485 Medical Devices – Quality Management Systems – Requirements for Regulatory Purposes
EN 1041 Information Supplied by the Manufacturer of Medical Devices
BS EN 980 Graphical Symbols for Use in the Labeling of Medical Devices
ISO 14155 Clinical Investigation of Medical Devices for Human Subjects – Good Clinical
L. Test Principle:
The Exalenz BreathID® Hp System non-invasive breath test is a diagnostic test that analyzes a breath sample before and after ingestion of $^{13}\mathrm{C}$-enriched urea; it is used to identify those patients with *H. pylori* infection. The Exalenz BreathID® Hp System breath test is performed as follows: a $75\,\mathrm{mg}\,^{13}\mathrm{C}$-urea tablet and $4.3\,\mathrm{g}$ Citrica Powder are dissolved in water, and the resulting solution is ingested by the patient. The presence of the Citrica creates an acidic environment in the stomach and also delays the transfer of the ingested solution to the duodenum. These two characteristics facilitate the decomposition of the urea by *H. pylori*, if present. Thus, in the presence of urease associated with gastric *H. pylori*, $^{13}\mathrm{C}$-urea is decomposed to $^{13}\mathrm{CO}_2$ and $\mathrm{NH}_3$ according to the following equation:
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$$
\begin{array}{l}
\text{H. pylori urease} \\
2^{13}\text{C-urea} + 2\text{H}_2\text{O} \quad \rightarrow \quad 2^{13}\text{CO}_2 + 2\text{NH}_3
\end{array}
$$
The $^{13}\text{CO}_2$ is absorbed into the blood and then exhaled in the breath. Absorption and distribution of $^{13}\text{CO}_2$ is fast. Therefore, the cleavage of urea by the H. pylori urease that produces the $^{13}\text{CO}_2$ occurs immediately after the solution is ingested and enables immediate detection of increased $^{13}\text{CO}_2$ in the exhaled breath of H. pylori-positive patients.
In the case of H. pylori-negative patients, the $^{13}\text{C-urea}$ does not produce $^{13}\text{CO}_2$ in the stomach because there are no human enzymes that can metabolize the urea in the stomach.
The BreathID Hp Lab System consists of the BreathID Hp Device, an Auto Sampler, and the computer based BreathID Hp Lab application with a Work Station. In addition, the BreathID Hp Lab System is used with the IDkit:Hp™ TWO test kit. The subject system enables sample collection into breath sample bags, instead of using a nasal cannula. Breath sample bag collection enables off site and deferred testing as compared to on-line measurement when using the nasal cannula. The BreathID Hp Lab System with the IDkit:Hp™ TWO test kit enables testing of multiple breath sample bags sequentially using the Auto Sampler. A maximum of ten pairs of bags (Baseline and Post Ingestion) can be attached to the Auto Sampler in 20 ports, for measurement on the BreathID® Hp Device. The Lab Application controls the automated process and presents the results.
Patients first fill a Baseline Breath Sample Bag with their breath prior to ingestion of the $^{13}\text{C-urea}$ test drink, and then fill a Post-Ingestion Breath Sample Bag 15 minutes after ingestion. The bags are color-coded to mitigate the risk of mixing-up the patient samples collected before and after consuming the test drink. One (1) DOB measurement detecting the change in the $^{13}\text{CO}_2/^{12}\text{CO}_2$ ratio is sufficient since the Post-Ingestion Breath Sample Bag contains breath collected 15 minutes after consumption of the test drink.
Immediately following the conclusion of the test, the system prints a summary of the test results.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
**Reproducibility**
Analytical studies were conducted to evaluate the reproducibility and precision of the BreathID® Hp Lab System with different operators, instruments, days, and sites. The studies used samples stored up to 14 days at different temperature and humidity conditions.
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Three gas isotope pairs were used with Delta Over Baseline (DOB) values of 3.3 (high negative), 6.4 (low positive), and 15.5 (moderate positive). Two operators were asked to operate each of three BreathID® Hp Lab Systems at three different sites for five days to measure the DOB values for samples from each of the three sample pairs. The results demonstrated that the standard deviation and overall reproducibility were stable over different samples for both the operator, the devices and between days. The reproducibility standard deviation was 0.65 or less for all samples, and the between days, devices and operators standard deviation was 0.66 or less in all cases, which is less than the natural variability of the DOB measurement. Table 1 summarizes the results of the reproducibility study.
Table 1: Reproducibility Study Results
| Expected DOB | Parameter | SD Value | 95% CI | CV |
| --- | --- | --- | --- | --- |
| DOB: 3.3‰High Negative | Reproducibility | 0.53 | [0.46 - 0.63] | 14.8% |
| | Between Days Precision | 0.54 | [0.46 - 0.60] | 14.9% |
| | Between Devices Precision | 0.54 | [0.45 - 0.59] | 14.9% |
| | Between Operators Precision | 0.53 | [0.44 - 0.58] | 14.8% |
| DOB: 6.4‰Low Positive | Reproducibility | 0.60 | [0.52 - 0.71] | 9.7% |
| | Between Days Precision | 0.62 | [0.54 - 0.68] | 10.0% |
| | Between Devices Precision | 0.60 | [0.51 - 0.65] | 9.7% |
| | Between Operators Precision | 0.60 | [0.51 - 0.70] | 9.7% |
| DOB: 15.5‰Moderate Positive | Reproducibility | 0.65 | [0.57 - 0.77] | 4.3% |
| | Between Days Precision | 0.65 | [0.56 - 0.72] | 4.3% |
| | Between Devices Precision | 0.66 | [0.56 - 0.73] | 4.4% |
| | Between Operators Precision | 0.65 | [0.55 - 0.76] | 4.3% |
# Precision (Repeatability)
Three gas isotope pairs were used with DOB values of 3.3 (high negative), 6.4 (low positive), and 15.5 (moderate positive). The DOB values for each of the samples were measured on the BreathID® Hp Lab System twice a day for 12 days. The results demonstrated that the standard deviation and overall repeatability were stable over different samples and different days. The repeatability standard deviation was 0.64 or less and the overall between days standard deviation was 0.72 or less, which is less than the natural variability of the DOB measurement. Table 2 summarizes the results of the precision study.
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Table 2: Precision Study Results
| Expected DOB | Parameter | SD Value | 95% CI | CV |
| --- | --- | --- | --- | --- |
| DOB: 3.3‰ | Repeatability | 0.56 | [0.44 - 0.78] | 16.9% |
| | Between Days Precision | 0.63 | [0.52 - 0.80] | 17.4% |
| DOB: 6.4‰ | Repeatability | 0.59 | [0.46 - 0.82] | 9.2% |
| | Between Days Precision | 0.68 | [0.56 - 0.87] | 10.6% |
| DOB: 15.5‰ | Repeatability | 0.64 | [0.50 - 0.89] | 4.3% |
| | Between Days Precision | 0.72 | [0.60 - 0.92] | 4.8% |
b. Linearity/assay reportable range:
Not applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Not applicable
# Stability of breath sample bags
An analytical study was conducted to evaluate the stability of breath sample bags at the maximum limits of the recommended storage times and conditions. One gas isotope pair was used in a bench study. Pairs of breath sample bags with a DOB value of 3.3 were stored at two different storage conditions representing the two extreme temperatures of the recommended storage range, $15^{\circ}\mathrm{C}$ and $35^{\circ}\mathrm{C}$ , and at the high limit of the recommended relative humidity (RH), $70\%$ . The DOB values for samples from each storage condition were measured on the BreathID® Hp Lab System seven times during 14 consecutive days for each storage condition, on days 2, 4, 8, 9, 10, 11 and 14. The results demonstrated that the standard deviation and overall repeatability were stable over different samples, different days and different storage conditions. The overall repeatability standard deviation and the between days precision standard deviation were 0.60 or less, which is less than the natural variability of the DOB measurement. Table 3 summarizes the results of the breath sample bags stability study.
Table 3: Bags Storage Study Results
| Expected DOB | Storage Condition | Parameter | SD Value | 95% CI | CV |
| --- | --- | --- | --- | --- | --- |
| DOB: 3.3‰ | 15°C | Overall Repeatability | 0.57 | [0.45 - 0.78] | 15.0% |
| | | Between Days Precision | 0.57 | [0.45 - 0.68] | 15.0% |
| | 35°C + RH 70% | Overall Repeatability | 0.60 | [0.48 - 0.82] | 16.9% |
| | | Between Days Precision | 0.60 | [0.47 - 0.72] | 16.9% |
d. Detection limit:
Not applicable
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e. Analytical specificity:
Carry-over testing
A study was conducted to evaluate the potential for sample to sample carry-over or cross contamination in the BreathID Hp Lab system. Twenty runs were conducted using the sequence recommended in CLSI EP10 using contrived gas, each run consisting of 10 tests. Data from tests 2-10 in each run were used in the analysis as instructed in CLSI EPI0. The acceptance criteria were as follows:
Accuracy
For measurement range 0-5 DOB: ±1.0
For measurement range 5 DOB and up: ±20% of the expected result
Precision
Standard deviation: ±1.0 DOB
The allowable bias and imprecision (CV%, coefficient of variation) for each gas level were derived from these requirements:
Allowable bias:
For low level (DOB = 3): ±1.0
For mid-level (DOB = 9): ±20% x 9 = 1.8
For high level (DOB = 15): ±20% x 15 = 3
Allowable imprecision (CV%):
The coefficient of variation is the ratio of the standard deviation to the mean. For calculating CV% limit, the allowable standard deviation of the system (1.0) was divided by the expected DOB result.
For the low level: -30%
For mid-level: - 11%
For the high level: - 6.5%
The observed bias and imprecision values were acceptable for all three concentrations. There was no evidence carry-over or cross contamination in the study. The results are summarized in Table 4 below.
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Table 4: Carry-over testing results
| | Low Level | | | Mid Level | | | High Level | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Day | Within-run STD | Within-run variance | Mean | Within-run STD | Within-run variance | Mean | Within-run STD | Within-run variance | Mean |
| 1 | 0.445 | 0.198 | 3.4 | 0.785 | 0.616 | 8.635 | 0.592 | 0.350 | 15 |
| 2 | 0.683 | 0.466 | 3.235 | 0.408 | 0.166 | 8.815 | 0.756 | 0.573 | 14.93 |
| 3 | 0.364 | 0.133 | 3.15 | 0.537 | 0.288 | 8.62 | 0.578 | 0.334 | 14.95 |
| 4 | 0.320 | 0.103 | 3.3 | 0.783 | 0.613 | 8.9 | 0.730 | 0.533 | 14.85 |
| 5 | 0.478 | 0.228 | 3.1 | 0.476 | 0.227 | 8.965 | 0.308 | 0.095 | 15.2 |
| 6 | 0.542 | 0.294 | 3.22 | 0.766 | 0.587 | 8.535 | 0.589 | 0.347 | 14.785 |
| 7 | 0.809 | 0.655 | 3.4 | 0.541 | 0.293 | 8.75 | 0.617 | 0.381 | 14.385 |
| 8 | 0.750 | 0.563 | 3.32 | 0.435 | 0.19 | 8.65 | 0.416 | 0.173 | 14.88 |
| 9 | 0.441 | 0.195 | 3.25 | 0.513 | 0.2635 | 8.92 | 0.618 | 0.383 | 15.05 |
| 10 | 0.177 | 0.0315 | 3.235 | 0.446 | 0.199 | 8.5 | 0.553 | 0.306 | 14.765 |
f. Assay cut-off:
The cut-off value is 5.0 Delta Over Baseline (DOB). Values below 5.0 DOB are interpreted as negative and values greater than or equal to 5.0 are interpreted as positive.
2. Comparison studies:
a. Method comparison with predicate device:
Not applicable
b. Matrix comparison:
Not applicable
3. Clinical studies:
a. Clinical Sensitivity:
A multi-center, non-randomized, open label, validation, pivotal study was conducted to demonstrate the efficacy of the IDkit $\mathrm{Hp}^{\mathrm{TM}}$ Two as part of the BreathID® Hp Lab System for initial diagnosis and post eradication testing versus composite biopsy results (histology and RUT or culture). The study used the 5 DOB diagnostic cut-off.
Patients were asked to produce two pairs of breath samples with bags from the IDkit $\mathrm{Hp}^{\mathrm{TM}}$ Two, and the sample analysis was performed either on site or in a remote location using a BreathID® Hp Lab System.
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The study was conducted at 11 United States clinical sites and two sites in Israel. A total of 189 adult initial diagnosis patients and 68 post-therapy patients were enrolled. Post-therapy patients were positive for infection had completed eradication therapy at least six weeks prior to participation in the study.
Patients were evaluated by at least three diagnostic methods:
1. Histopathology: Biopsy specimens, fixed with formalin, were cut into sections, stained with at least H&E and IHC stains, and examined by an experienced pathologist at a central laboratory.
2. Rapid Urease Test (RUT): Biopsy specimens were tested for urease activity with a FDA-cleared test according to the instructions in its package insert.
3. Exalenz BreathID® Hp Lab test: The Exalenz BreathID® Hp Lab test was performed in accordance with the procedures described in the IDkit: Hp™ Two package insert.
Pre-Therapy Results
Table 5: Comparison of the BreathID® Hp Lab Test using IDkit Hp™ Two to Composite Reference Method (RUT and histological exam) Pre-Therapy
| | Composite Reference Method* | | |
| --- | --- | --- | --- |
| BreathID Hp Lab test using IDkit Hp™ Two | Positive | Negative | Total |
| Positive | 37 | 3 | 40 |
| Negative | 0 | 139 | 139 |
| Total | 37 | 142 | 179 |
*H. pylori positive is defined as positive rapid urea test and positive histology.
H. pylori negative is defined as negative rapid urea test and negative histology.
10 breath samples were excluded from the analysis because they were classified as "not evaluable". "Not evaluable" sample are classified as either positive rapid urease and negative histology or negative rapid urease and positive histology.
Sensitivity: 100% [95% CI (90.60; 100.00)]
Specificity: 97.9% [95% CI (93.97; 99.28)]
Post-Therapy Results
Table 6: Comparison of the BreathID Hp Lab Test using IDkit Hp™ Two to Composite Reference Method Post-Therapy
| | Composite Reference Method* | | |
| --- | --- | --- | --- |
| BreathID Hp Lab test using IDkit Hp™ Two | Positive | Negative | Total |
| Positive | 12 | 0 | 12 |
| Negative | 1 | 55 | 55 |
| Total | 13 | 56 | 68 |
*H. pylori positive is defined as positive RUT or positive Histology
H. pylori negative is defined as negative RUT and negative Histology
Sensitivity: 92.3% [95% CI (66.69; 98.63)]
Specificity: 100% [95% CI (93.47; 100.00)]
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Stability of clinical breath samples
To further demonstrate the stability of breath samples after storage over time in the breath sample collection bags, 191 initial diagnosis patients were asked to perform the urea breath test using two sets of IDkit Hp™ Two test kit. The sample analysis was performed either on-site or in a remote location using a BreathID® Hp Lab System. Each pair of breath sample bags was analyzed at a different time point up to 14 days apart in order to assess the stability of the breath samples in the bags. A total of 191 subjects produced two results that were evaluable for analysis. Out of 45 samples positive on the first measurement, 44 remained positive on the second measurement (Percent Positive Agreement: 97.8% [95% CI (88.43, 99.61)]). Out of 146 samples negative on the first measurement, all 146 remained negative on the second measurement (Percent Negative Agreement: 100% [95% CI (97.44, 100)])
b. Clinical specificity:
See section M3a above
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable
4. Clinical cut-off:
Not applicable
5. Expected values/Reference range:
The expected values of the BreathID® Hp Lab System are originally calculated in K011668 and presented below:
Upper 97.5% percentile of the Negative patients: 2.245
Lower 2.5% percentile of the Positive patients: 7.212
N. Instrument Name:
Exalenz BreathID Hp Lab System
O. System Descriptions:
1. Modes of Operation:
Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?
Yes ☐ X or No ☐
Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?
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Yes ☐ or No ☑
2. Software:
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:
Yes ☐ or No ☑
3. Specimen Identification:
Specimens IDs can be entered in manually or through a barcode reader.
4. Specimen Sampling and Handling:
Specimens for the BreathID Hp Lab System acquires breath exhaled through the mouth into the breath collection bags (IDkit Hp Two test kit) before and after taking the $^{13}\mathrm{C}$-enriched urea substrate. Specimens collected in bags can be measured up to 14 days from the moment the bags were filled with patient-exhaled breath.
Updates for the Exalenz BreathID Hp Lab System include an Auto Sampler with its embedded software and the BreathIDLab Application with its Work Station, which permits the automated consecutive batch measurement of up to 10 pairs of breath bags (before and after ingestion of $^{13}\mathrm{C}$-enriched urea).
5. Calibration:
Calibration is performed by the instrument with five gas samples of known concentration and isotope ratio are used to adjust the absorption cell calibration curves, aiming to attain identical isotope ratios over the collection range of $\mathrm{CO}_{2}$ concentrations. This will ensure accurate readings in both negative and positive samples. The device uses these five concentrations to determine the systematic error of the system and to ensure that the estimated systematic error is below a specified value. If the systematic error is not below the specified value, the device prompts the user to contact Exalenz for repair or replacement.
6. Quality Control:
To ensure correct functioning of the BreathID Hp Lab System in the field, a self test is required every 75 breath tests. BreathID Hp Lab System will automatically perform a self test after 75 tests are completed, during the baseline measurement phase of the next patient test. This procedure confirms that the BreathID Hp Lab System is functional and is performing within specifications.
P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:
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Additional secondary analysis was performed for both Pre-Therapy and Post-Therapy. In the secondary analysis the UBT results were compared to each of the two components of the Composite Reference Method, Rapid Urease Test (RUT) and Histology separately. The four tables below summaries the performance for each test separately.
Table 7: Comparison of the BreathID® Hp Lab Test using IDkit Hp™ Two to Rapid Urease Test (RUT) Pre-Therapy
| | BreathID® Hp Lab test using IDkit | | |
| --- | --- | --- | --- |
| RUT | Positive | Negative | Total |
| Positive | 37 | 5 | 42 |
| Negative | 7 | 140 | 147 |
| Total | 44 | 145 | 189 |
Percent Positive Agreement: $88.1\%$ [95% CI (75.00; 94.81)]
Percent Negative Agreement: $95.2\%$ [95% CI (90.50; 97.67)]
Table 8: Comparison of the BreathID® Hp Lab Test using IDkit Hp™ Two to Histology Pre-Therapy
| | BreathID® Hp Lab test using IDkit | | |
| --- | --- | --- | --- |
| Histology | Positive | Negative | Total |
| Positive | 41 | 1 | 42 |
| Negative | 3 | 144 | 147 |
| Total | 44 | 145 | 189 |
Percent Positive Agreement: $97.6\%$ [95% CI (87.68; 99.58)]
Percent Negative Agreement: $98.0\%$ [95% CI (94.17; 99.30)]
Table 9: Comparison of the BreathID® Hp Lab Test using IDkit Hp™ Two to RUT Post-Therapy
| | BreathID® Hp Lab test using IDkit | | |
| --- | --- | --- | --- |
| RUT | Positive | Negative | Total |
| Positive | 11 | 0 | 11 |
| Negative | 1 | 56 | 57 |
| Total | 12 | 56 | 68 |
Percent Positive Agreement: $100\%$ [95% CI (74.12; 100)]
Percent Negative Agreement: $98.25\%$ [95% CI 90.71; 99.69)]
Table 10: Comparison of the BreathID® Hp Lab Test using IDkit Hp™ Two to Histology Post-Therapy
| | BreathID® Hp Lab test using IDkit | | |
| --- | --- | --- | --- |
| Histology | Positive | Negative | Total |
| Positive | 12 | 1 | 13 |
| Negative | 0 | 55 | 55 |
| Total | 12 | 56 | 68 |
Percent Positive Agreement: $92.3\%$ [95% CI (66.69; 98.63)]
Percent Negative Agreement: $100\%$ [95% CI (93.47; 100)]
{14}
Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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