(124 days)
Not Found
No
The summary describes a device using solid-state electrochemical sensor technology and pneumatics for quantitative measurement. There is no mention of AI, ML, or any algorithms that would suggest their use in data processing or interpretation beyond standard signal processing for the sensor. The performance studies focus on accuracy, precision, linearity, and interference, which are typical for sensor-based measurement devices, not AI/ML model validation.
No
The Fenom Pro™ Nitric Oxide Test measures FeNO to monitor the therapeutic effect of anti-inflammatory treatment for asthma, but it does not administer therapy itself. Therefore, it is a diagnostic/monitoring device, not a therapeutic one.
Yes
The device is described as a "portable, non-invasive device to measure fractional exhaled nitric oxide (FeNO) in human breath" and FeNO is stated to be "increased in some airway inflammatory processes, such as asthma." It measures FeNO as "an indication of therapeutic effect in patients with elevated FeNO levels" and measurements are to be used "as an adjunct to established clinical assessments." While it's used to monitor therapeutic effect, the measurement of a physiological marker (FeNO) that indicates an inflammatory process (like asthma) is a form of diagnostic support, helping clinicians assess a patient's condition.
No
The device description explicitly states it is comprised of four major hardware components: a main unit containing a touch screen, sensor, and pneumatics; a mouthpiece; a handpiece; and a breath conditioning cartridge. It is a physical breath analyzer, not software only.
Yes, the Fenom Pro™ Nitric Oxide Test is an In Vitro Diagnostic (IVD) device.
Here's why:
- Intended Use: The device is intended to measure fractional exhaled nitric oxide (FeNO) in human breath. This measurement is used as an adjunct to established clinical assessments to indicate therapeutic effect of anti-inflammatory treatment in asthma patients with elevated FeNO levels. This involves analyzing a biological sample (exhaled breath) to provide information about a physiological state (airway inflammation and response to treatment).
- Device Description: It's a "point-of-care breath analyzer" that uses a sensor to measure a component (nitric oxide) in a biological sample (exhaled breath).
- Clinical Data: The clinical studies described involve measuring FeNO in human subjects and correlating these measurements with clinical outcomes (response to therapy, spirometry, asthma questionnaires). This is typical of IVD device validation.
- Predicate Device: The predicate device listed, NIOX MINO, is also an FeNO measurement device and is classified as an IVD.
While it doesn't perform a traditional binary diagnostic test (like positive/negative for a disease), it provides a quantitative measurement from a biological sample that is used to aid in clinical assessment and monitoring of a medical condition (asthma). This falls under the definition of an IVD.
N/A
Intended Use / Indications for Use
Fenom Pro™ Nitric Oxide Test is a portable, non-invasive device to measure fractional exhaled nitric oxide (FeNO) in human breath. FeNO is increased in some airway inflammatory processes, such as asthma, and often decreases in response to anti-inflammatory treatment of FeNO by Fenom Pro™ is a method to measure the decrease in FeNO concentration in asthma patients that often occurs after treatment with anti-inflammatory pharmacological therapy as an indication of therapeutic effect in patients with elevated FeNO levels. FeNO measurements are to be used as an adjunct to established clinical assessments. Fenom Pro™ is suitable for children, approximately 7-17 years, and adults 18 years and older.
Testing using the Fenom Pro™ should only be done in a point-of-care healthcare setting under professional supervision. Fenom Pro™ should not be used in critical care, emergency care or in anesthesiology.
Product codes (comma separated list FDA assigned to the subject device)
MXA
Device Description
Fenom Pro™ is a point-of-care breath analyzer that uses solid-state electrochemical technology to measure the fraction of exhaled nitric oxide (FeNO), a marker for airway inflammation, in human exhaled breath. Measurement of FeNO by Fenom Pro is a quantitative and non-invasive method to indicate therapeutic effects of anti-inflammatory pharmacological therapy in patients with elevated FeNO levels. Fenom Pro™ is suitable for children, approximately 7-17 years, and adults 18 years and older.
Fenom Pro uses solid state, potentiometric, sensor technology sensitive to nitric oxides (NO) compounds. The solid state sensor is fluidly preceded by a reactive filter material that renders (oxidizes) potentially confounding species such as carbon monoxide (CO), ammonia (NH4), and methanol (CH4O) inactive, or inert, to the NO sensor. Fenom Pro provides visual and audible feedback during its use. The visual and audible feedback is especially important during the FeNO measurement such that the user can modulate their breath speed within the flow parameters required by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) standards.
Fenom Pro is comprised of four major components. The main unit contains a touch screen interface for the use as well as houses the nitric oxide sensor and pneumatics needed to sample the patient's breath. The patient interfaces with Fenom though the mouthpiece which is attached to the handpiece. The handpiece is connected to the main unit via a breath tube. The handpiece contains a breath conditioning cartridge which prepares the breath sample from the patient for proper analysis in the main unit. Both the mouthpiece and the breath conditioning cartridge are consumables.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
children, approximately 7-17 years, and adults 18 years and older.
Intended User / Care Setting
point-of-care healthcare setting under professional supervision.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Nonclinical Data:
- Accuracy and Environmental Testing: Two devices tested over three concentrations with five replicates each at 5 different environmental conditions (Ambient Temp/Humidity, Low Temp/Low Humidity, High Temp/Low Humidity, Low Temp/High Humidity, High Temp/High Humidity). Nitric oxide mixed in a balance gas of simulated breath measured using a chemiluminescence device. All tests passed the accuracy acceptance criteria (+/-5ppb for 15ppb, +/-10% for 75ppb and 200ppb).
- Precision: Based on CLSI EP05-A3 (80 replicates per sample per device). Data collected from 5 devices over 5 operating days, 2 sessions per day, 4 runs per session with 2 replicates for each concentration (10, 25, 75, 200 ppb), by multiple operators.
- Linearity: 8 NO concentration levels (5, 10, 15, 30, 50, 100, 150, 200 ppb) tested in five replicates across two devices. Linear regression of the device compared to a reference measurement showed slope between 1.02 and 1.03 and R values of 0.998 to 0.999.
- Limit of Detection: Based on CLSI-EP17-A2. Two devices tested at 0 ppb (60 replicates), 5 ppb (30 replicates) and 10 ppb (30 replicates) over three days. LoD calculated as 1.8 ppb and 4.6 ppb, both less than the 10 ppb spec requirement.
- Interference Testing - other gasses: Tested sensor interference levels for various substances (Acetaldehyde, Acetone, Acetonitrile, Ammonia, Carbon Dioxide, Carbon Monoxide, Ethanol, Hydrogen, Hydrogen Sulfide, Isoprene, Hydrogen Peroxide, Oxygen). No observed interferences causing a response larger than a 4 ppb NO equivalent response, except for acetonitrile which is relevant only for smokers.
- Interference Testing - Exogenous Substances: Study with seven commonly used oral substances (Alcohol Free Mouthwash, Caffeinated Soda, Caffeine Free Soda, Menthol Lozenge, Mouthwash with Alcohol, Non-Mentol Lozenge, Toothpaste). Minimum of 10 volunteers per substance. Fenom Pro levels measured at baseline, 10 minutes, and 60 minutes after exposure. Mean differences between 60 minutes and baseline were within 5 ppb and 95% confidence intervals included zero, indicating no impact.
Clinical Data:
- Clinical Precision (User Bias): Mixed study population of 127 subjects (44 pediatric, 83 adults). Subjects obtained two Fenom Pro measurements with assistance of three HCPs (total six evaluations per subject). Maximum mean bias observed was 1.2 ppb between pairs of HCPs. Very high quantitative agreement demonstrated by Deming regression, correlation, and bias analyses (Pearson R ranging from 0.9873 to 0.9945).
- Within Subject Precision: Assessed from the 127 subject study population, subgrouped by age. Clinical imprecision was less than 5ppb (mean standard deviation for FeNO values below 50ppb), and %CVs for FeNO values greater than 50ppb were maintained at less than 10% (unless sample size was small).
- Clinical Efficacy (Longitudinal Study): 82 subjects (37 aged 5-17, 45 aged 18+) with uncontrolled asthma. Measurements for FeNO, spirometry, and asthma questionnaires completed at baseline (Visit 1) and two weeks later (Visit 2) after therapeutic agents were administered. Demonstrated significant differences between visits for all three modalities, showing concordance between Fenom Pro and established asthma-related outcome measures (FEV1 and ACQ/pACQ). Kendall's Tau p-values were 0.0370 for FeNO vs. FEV1 and 0.0125 for FeNO vs. ACQ/pACQ.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Accuracy: +/-5ppb for 15ppb, +/-10% for 75ppb and 200ppb concentrations.
- Limit of Detection (LoD): 1.8 ppb and 4.6 ppb measured, both 50ppb (with small sample size exceptions).
- Kendall's Tau point estimate: -0.1599 (FeNO vs. FEV1) and 0.1931 (FeNO vs. ACQ/pACQ).
- Kendall's Tau p-value: 0.0370 (FeNO vs. FEV1) and 0.0125 (FeNO vs. ACQ/pACQ).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
NIOX MINO, K072816
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.3080 Breath nitric oxide test system.
(a)
Identification. A breath nitric oxide test system is a device intended to measure fractional nitric oxide in human breath. Measurement of changes in fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of asthma. A breath nitric oxide test system combines chemiluminescence detection of nitric oxide with a pneumotachograph, display, and dedicated software.(b)
Classification. Class II (special controls). The special control is FDA's guidance entitled “Class II Special Controls Guidance Document: Breath Nitric Oxide Test System.” See § 862.1(d) for the availability of this guidance document.
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services logo on the left, and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" in a square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in a sans-serif font.
February 13, 2019
Spirosure, Inc. % Erika Ammirati, President Ammirati Regulatory Consulting 575 Shirlynn Court Los Altos, CA 94022
Re: K182874
Trade/Device Name: Fenom ProTM Nitric Oxide Test Regulation Number: 21 CFR 862.3080 Regulation Name: Breath nitric oxide test system Regulatory Class: Class II Product Code: MXA Dated: January 11, 2019 Received: January 15, 2019
Dear Erika Ammirati:
We have reviewed vour 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 Mav 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you. however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal
1
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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K182874
Device Name Fenom Pro™ Nitric Oxide Test
Indications for Use (Describe)
Fenom Pro™ Nitric Oxide Test is a portable, non-invasive device to measure fractional exhaled nitric oxide (FeNO) in human breath. FeNO is increased in some airway inflammatory processes, such as asthma, and often decreases in response to anti-inflammatory treatment of FeNO by Fenom Pro™ is a method to measure the decrease in FeNO concentration in asthma patients that often occurs after treatment with anti-inflammatory pharmacological therapy as an indication of therapeutic effect in patients with elevated FeNO levels. FeNO measurements are to be used as an adjunct to established clinical assessments. Fenom Pro™ is suitable for children, approximately 7-17 years, and adults 18 years and older.
Testing using the Fenom Pro™ should only be done in a point-of-care healthcare setting under professional supervision. Fenom Pro™ should not be used in critical care, emergency care or in anesthesiology.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| ------------------------------------------------------------- | ------------------------------------------------------------ |
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3
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is K182874. This document was
| 807.92 (a)(1): Name:
Address: | Spirosure, Inc.
7020 Koll Center Parkway, Suite 110
Pleasanton, CA 94566 |
|----------------------------------|--------------------------------------------------------------------------------|
| Phone:
Email:
Contact: | (925) 264-7720
ryan@spirosure.com
Mr. Ryan Leard |
Date of Preparation: October 11, 2018
807.92 (a)(2): Device name- trade name and common name, and classification
Trade name: Fenom Pro™ Nitric Oxide Test
Common Name: Breath nitric oxide test system
Classification: 21 CFR Part 862.3080
807.92 (a)(3): Identification of the legally marketed predicate devices NIOX MINO (Aerocrine AB, Morrisville, NC), K072816
807.92 (a)(4): Device Description
Fenom Pro™ is a point-of-care breath analyzer that uses solid-state electrochemical technology to measure the fraction of exhaled nitric oxide (FeNO), a marker for airway inflammation, in human exhaled breath. Measurement of FeNO by Fenom Pro is a quantitative and non-invasive method to indicate therapeutic effects of anti-inflammatory pharmacological therapy in patients with elevated FeNO levels. Fenom Pro™ is suitable for children, approximately 7-17 years, and adults 18 years and older.
Fenom Pro uses solid state, potentiometric, sensor technology sensitive to nitric oxides (NO) compounds. The solid state sensor is fluidly preceded by a reactive filter material that renders (oxidizes) potentially confounding species such as carbon monoxide (CO), ammonia (NH4), and methanol (CH4O) inactive, or inert, to the NO sensor. Fenom Pro provides visual and audible feedback during its use. The visual and audible feedback is especially important during the FeNO measurement such that the user can modulate their breath speed within the flow parameters required by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) standards.
Fenom Pro is comprised of four major components. The main unit contains a touch screen interface for the use as well as houses the nitric oxide sensor and pneumatics needed to sample the
4
patient's breath. The patient interfaces with Fenom though the mouthpiece which is attached to the handpiece. The handpiece is connected to the main unit via a breath tube. The handpiece contains a breath conditioning cartridge which prepares the breath sample from the patient for proper analysis in the main unit. Both the mouthpiece and the breath conditioning cartridge are consumables.
807.92 (a)(5): Intended Use
Fenom Pro™ Nitric Oxide Test is a portable, non-invasive device to measure fractional exhaled nitric oxide (FeNO) in human breath. FeNO is increased in some airway inflammatory processes, such as asthma, and often decreases in response to anti-inflammatory treatment of FeNO by Fenom Pro™ is a method to measure the decrease in FeNO concentration in asthma patients that often occurs after treatment with anti-inflammatory pharmacological therapy as an indication of therapeutic effect in patients with elevated FeNO measurements are to be used as an adjunct to established clinical assessments. Fenom Pro™ is suitable for children, approximately 7-17 years, and adults 18 years and older.
Testing using the Fenom Pro™ should only be done in a point-of-care healthcare setting under professional supervision. Fenom Pro™ should not be used in critical care, emergency care or in anesthesiology.
807.92 (a)(6): Technological Similarities and Differences to the Predicate
The following chart describes similarities and differences between Fenom Pro™ and the predicate.
| Comparison | Subject Device
Fenom Pro™ Nitric Oxide Test | Predicate Device
NIOX MINO
(K072816) |
|--------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Fenom Pro™ Nitric Oxide Test is a
portable, non-invasive device to measure
fractional exhaled nitric oxide (FeNO) in
human breath. FeNO is increased in
some airway inflammatory processes,
such as asthma, and often decreases in
response to anti-inflammatory treatment.
Measurement of FeNO by Fenom Pro™
is a method to measure the decrease in
FeNO concentration in asthma patients
that often occurs after treatment with
anti-inflammatory pharmacological
therapy as an indication of therapeutic
effect in patients with elevated FeNO
levels. FeNO measurements are to be
used as an adjunct to established clinical
assessments. Fenom Pro™ is suitable
for children, approximately 7-17 years,
and adults 18 years and older. | NIOX MINO® measures Nitric Oxide
(NO) in human breath. Nitric Oxide is
frequently increased in some
inflammatory processes such as
asthma. The fractional NO
concentration in expired breath
(FeNO), can be measured by NIOX
MINO according to guidelines for NO
measurement established by the
American Thoracic Society.
Measurement of FeNO by NIOX
MINO is a quantitative, non-invasive,
simple and safe method to measure the
decrease in FeNO concentration in
asthma patients that often occurs after
treatment with anti-inflammatory
pharmacological therapy, as an
indication of the therapeutic effect in
patients with elevated FeNO levels.
NIOX MINO is suitable for children. |
| | | |
| | Testing using the Fenom Pro™ should
only be done in a point-of-care
healthcare setting under professional
supervision. Fenom Pro™ should not be
used in critical care, emergency care or
in anesthesiology. | approximately 7 - 17 years, and adults
18 years and older.
FeNO measurements provide the
physician with means of evaluating an
asthma patient's response to anti-
inflammatory therapy, as an adjunct to
the established clinical and laboratory
assessments in asthma. The NIOX
MINO is intended for prescription use
and should only be used as directed in
the NIOX MINO User Manual by
trained healthcare professionals. NIOX
MINO cannot be used with infants or
by children approximately under the
age of 7, as measurement requires
patient cooperation. NIOX MINO
should not be used in critical care,
emergency care or in anesthesiology. |
| Class | Class II | Same |
| Regulation Number | 21 CFR 862.3080 | Same |
| Product Code | MXA | Same |
| FDA Branch | Toxicology/Chemistry (75) | Same |
| Result Type | Quantitative | Same |
| Test Locale | Point-of-Care, Professional | Same |
| Sample Type | Exhaled human breath | Same |
| Test Principle | Electrochemical sensor technology | Same |
| Sensor Calibration | Factory Calibrated | Same |
| Measurement Range | 10-200ppb NO | 5-300ppb NO |
| Detection Level | 10ppb | 5ppb |
| Analysis Time | approximately 30 seconds | approximately one minute |
| Power Supply | 100-240V, ~50-60Hz | 100-240V, ~47-63Hz |
5
6
807.92 (b)(1): Brief Description of Nonclinical Data
Accuracy and Environmental Testing
Two devices were tested over three concentrations with five replicates each at 5 different environmental conditions for a total of 150 tests. The five different conditions tested are summarized in the table below .
| Tested Conditions | |||
|---|---|---|---|
| Test Case | Test Case Description | Temperature (°C) | Relative Humidity (%RH) |
| 1 | Ambient Temp / Ambient Humidity | 22° | 37% |
| 2 | Low Temp / Low Humidity | 15° | 20% |
| 3 | High Temp / Low Humidity | 30° | 20% |
| 4 | Low Temp / High Humidity | 15° | 80% |
| 5 | High Temp / High Humidity | 30° | 80% |
For each concentration, nitric oxide was mixed in a balance gas of simulated breath. Each concentration sample was measured using a chemiluminescence device calibrated against a NIST traceable NO tank. This measurement was used to calculate the device error for each replicate. The data are shown below.
| Test Case | Target Conc.
(ppb) | Device | Actual
Concentration
(ppb) | Mean Score
(ppb) | Std Dev Score
(ppb) | Upper 95%
Error Limit
(ppb/%) | Lower 95% Error
Limit (ppb/%) | Accuracy
Acceptance
Criterion | Pass/Fail |
|-----------------------|-----------------------|--------|----------------------------------|---------------------|------------------------|-------------------------------------|----------------------------------|-------------------------------------|-----------|
| Ambient T/ Ambient RH | 15 | GP18 | 14.5 | 13.6 | 0.548 | 0.17ppb | -1.97ppb | +/-5ppb | Pass |
| Ambient T/ Ambient RH | 15 | GP35 | 14.5 | 12.8 | 1.095 | 0.44ppb | -3.84ppb | +/-5ppb | Pass |
| Ambient T/ Ambient RH | 75 | GP18 | 70.1 | 70 | 0.707 | 1.83% | -2.12% | +/-10% | Pass |
| Ambient T/ Ambient RH | 75 | GP35 | 70.1 | 70.2 | 0.837 | 2.48% | -2.20% | +/-10% | Pass |
| Ambient T/ Ambient RH | 200 | GP18 | 187.5 | 185 | 0.707 | -0.59% | -2.07% | +/-10% | Pass |
| Ambient T/ Ambient RH | 200 | GP35 | 187.5 | 184.6 | 1.517 | 0.04% | -3.13% | +/-10% | Pass |
| High T/ High RH | 15 | GP18 | 14.5 | 16 | 1.225 | 3.90ppb | -0.90ppb | +/-5ppb | Pass |
| High T/ High RH | 15 | GP35 | 14.5 | 15.2 | 0.837 | 2.33ppb | -0.93ppb | +/-5ppb | Pass |
| High T/ High RH | 75 | GP18 | 70.1 | 68.8 | 1.643 | 2.74% | -6.45% | +/-10% | Pass |
| High T/ High RH | 75 | GP35 | 70.1 | 68.8 | 1.483 | 2.29% | -6.00% | +/-10% | Pass |
| High T/ High RH | 200 | GP18 | 187.5 | 182.8 | 2.683 | 0.30% | -5.31% | +/-10% | Pass |
| High T/ High RH | 200 | GP35 | 187.5 | 182 | 1.581 | -1.28% | -4.59% | +/-10% | Pass |
| High T/ Low RH | 15 | GP18 | 14.5 | 15 | 1.000 | 2.46ppb | -1.46ppb | +/-5ppb | Pass |
| High T/ Low RH | 15 | GP35 | 14.5 | 14.6 | 0.894 | 1.85ppb | -1.65ppb | +/-5ppb | Pass |
| High T/ Low RH | 75 | GP18 | 70.1 | 68.8 | 0.837 | 0.48% | -4.19% | +/-10% | Pass |
| High T/ Low RH | 75 | GP35 | 70.1 | 69 | 0.707 | 0.41% | -3.55% | +/-10% | Pass |
| High T/ Low RH | 200 | GP18 | 187.5 | 183 | 1.414 | -0.92% | -3.88% | +/-10% | Pass |
| High T/ Low RH | 200 | GP35 | 187.5 | 182.8 | 0.837 | -1.63% | -3.38% | +/-10% | Pass |
| Low T/ High RH | 15 | GP18 | 14.5 | 14.8 | 1.304 | 2.85ppb | -2.25ppb | +/-5ppb | Pass |
| Low T/ High RH | 15 | GP35 | 14.5 | 14.8 | 0.447 | 1.17ppb | -0.57ppb | +/-5ppb | Pass |
| Low T/ High RH | 75 | GP18 | 70.1 | 70.8 | 1.304 | 4.64% | -2.65% | +/-10% | Pass |
| Low T/ High RH | 75 | GP35 | 70.1 | 69.4 | 0.894 | 1.50% | -3.50% | +/-10% | Pass |
| Low T/ High RH | 200 | GP18 | 187.5 | 184.6 | 1.342 | -0.14% | -2.95% | +/-10% | Pass |
| Low T/ High RH | 200 | GP35 | 187.5 | 183.4 | 0.548 | -1.61% | -2.76% | +/-10% | Pass |
| Low T/ Low RH | 15 | GP18 | 14.5 | 14 | 0.000 | -0.5ppb | -0.5ppb | +/-5ppb | Pass |
| Low T/ Low RH | 15 | GP35 | 14.5 | 13.8 | 0.447 | 0.17ppb | -1.57ppb | +/-5ppb | Pass |
| Low T/ Low RH | 75 | GP18 | 70.1 | 68.2 | 1.095 | 0.35% | -5.77% | +/-10% | Pass |
| Low T/ Low RH | 75 | GP35 | 70.1 | 68.8 | 0.447 | -0.60% | -3.10% | +/-10% | Pass |
| Low T/ Low RH | 200 | GP18 | 187.5 | 174.4 | 2.702 | -4.16% | -9.81% | +/-10% | Pass |
| Low T/ Low RH | 200 | GP35 | 187.5 | 176.8 | 1.304 | -4.34% | -7.07% | +/-10% | Pass |
Accuracy Study Summary
7
Precision
The precision study was based on CLSI EP05-A3 (80 replicates per sample per device). Nitric oxide was mixed in a balance gas of simulated breath. Samples were measured using a chemiluminescence device calibrated against a NIST traceable NO tank. Data were collected from 5 devices over 5 operating days, 2 sessions per day, 4 runs per session with 2 replicates for each concentration, using the concentrations 10, 25, 75 and 200 ppb, by multiple operators. The data are shown below.
| Repeatability | ||||
|---|---|---|---|---|
| SD | ||||
| (ppb) | SD | |||
| (ppb) | %CV | %CV | ||
| Bag ID | 10 ppb | 25 ppb | 75 ppb | 200 ppb |
| GammaPrime02 | 1.6 | 1.8 | 3.7% | 3.9% |
| GammaPrime04 | 1.6 | 1.4 | 5.3% | 4.9% |
| GammaPrime05 | 1.2 | 1.5 | 4.0% | 3.0% |
| GammaPrime06 | 1.1 | 1.2 | 3.2% | 3.1% |
| GammaPrime07 | 1.9 | 2.3 | 7.1% | 7.3% |
Analytical Precision Summary
| Within-Device Precision | ||||
|---|---|---|---|---|
| SD | ||||
| (ppb) | SD | |||
| (ppb) | %CV | %CV | ||
| Bag ID | 10 ppb | 25 ppb | 75 ppb | 200 ppb |
| GammaPrime02 | 1.5 | 2.3 | 5.9% | 6.8% |
| GammaPrime04 | 1.5 | 1.7 | 6.2% | 6.2% |
| GammaPrime05 | 1.2 | 1.6 | 4.3% | 3.4% |
| GammaPrime06 | 1.2 | 1.2 | 4.0% | 4.5% |
| GammaPrime07 | 2.3 | 3.3 | 7.5% | 8.5% |
Linearity
Nitric oxide was mixed in a balance gas of simulated breath to obtain 8 NO concentration levels (5, 10, 15, 30, 50, 100, 150, 200 ppb). Samples were measured using a chemiluminescence device calibrated against a NIST traceable NO tank. Each concentration was tested in five replicates. Linearity was assessed across two devices. The linear regression of the device as compared to a reference measurement shall have a slope between 0.95 and 1.05 and 1.05 and 1.05 and 1.0 998.
| Linearity | |||
|---|---|---|---|
| Device | Slope | Intercept | R |
| GammaPrime42 | 1.03 | 2.32 | 0.999 |
| GammaPrime49 | 1.02 | 0.231 | 0.999 |
| Combined | 1.02 | 1.27 | 0.998 |
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Limit of Detection
The limit of detection study was based on CLSI-EP17-A2. Two devices were tested at 0 ppb (60 replicates), 5 ppb (30 replicates) and 10 ppb (30 replicates) over three days. Using the parametric option in CLSI-EP17-A2, the Limit of Detection (LoD) was calculated. The results are shown below.
| Device | Limit of Detection (ppb) | Spec Requirement (ppb) | Pass/Fail |
|---|---|---|---|
| Device #1 | 1.8 | 1 Analysis of exhaled breath from smokers and non-smokers by solid phase microextraction gas chromatography/mass spectrometry. Buszewski B, Ulanowska A, Ligor T, Denderz N, Amann A. Biomatogr. 2009 May23(5):51-6. doi: 10.1002/bmc.1141. |
2 Quantification of acetonitrile in exhaled breath and urings selected ion flow tube mass spectrometry. Abbott S.M., Elder J.B., Spanel P., Smith D. International Journal of Mass Spectrometry, Vol. 228, Issues 2-3, 2003 August 15, Pages 655-665.
9
Interference Testing- Exogenous Substances
A study was performed with seven commonly used oral substances (see below). A minimum of 10 volunteers per substance determined their baseline Fenom Pro levels, ingested or used the substance, and then repeated their Fenom Pro measurements 10 minutes and 60 minutes after the exposure. The 10-mintue data were for interest, only. For non-interference to be validated, the mean differences between 60 minutes and baseline values needed to be within 5 ppb. Further, the lower and upper 95% confidence intervals around the means needed to pass through zero.
| # | Exogenous Compound |
|---|---|
| 1 | Alcohol Free Mouthwash |
| 2 | Caffeinated Soda |
| 3 | Caffeine Free Soda |
| 4 | Menthol Lozenge |
| 5 | Mouthwash with Alcohol |
| 6 | Non-Menthol Lozenge |
| 7 | Toothpaste |
The data indicated that Fenom Pro was not impacted by any of the substances at 60 minutes.
| Exposure | Test
description | Mean
difference | Mean
difference
18 (n=83).
| Summary of Clinical Precision for FeNO measurements. Age group = ALL (n=127) | ||
|---|---|---|
| Median Concentrations | N | Within Subject Mean SD | 95% CI for SD | Within Subject Mean CV (%) | 95% CI for CV |
|---|---|---|---|---|---|
| 0 to =50 | 44 | 5.57 | 4.60, 7.05 | 5.94% | 4.91%, 7.52% |
| Median Concentrations | N | Within Subject
Mean SD | 95% CI for SD | Within Subject
Mean CV (%) | 95% CI for CV |
|-----------------------|----|---------------------------|---------------|-------------------------------|---------------|
| 0 to =50 | 20 | 5.74 | 4.36, 8.38 | 6.27% | 4.77%, 9.16% |
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| Median Concentrations | N | Within Subject
Mean SD | 95% CI for SD | Within Subject
Mean CV (%) | 95% CI for CV |
|-----------------------|----|---------------------------|---------------|-------------------------------|---------------|
| 0 to =50 | 24 | 5.43 | 4.22, 7.61 | 5.66% | 4.40%, 7.94% |
| Summary of Clinical Precision for FeNO measurements. Age group >= 18yrs (n=83) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| -- | -- | -- | -- | -- | -- | -- | -------------------------------------------------------------------------------- | -- | -- | -- | -- | -- | -- |
HCPs and subjects generally indicated favorable responses for the features of the device via their questionnaires. For the subject group, favorable impressions of the system were recorded approximately 93% of time; for the HCP group, favorable impressions of the system were recorded approximately 96% of time.
Clinical Precision was also assessed from a study that closely embodies the clinical use condition, where each subject provided replicate (n = 2) FeNO measurements at Visit 1 (baseline) and Visit 2 (after approximately two weeks of high dose corticosteroid therapy). The data were analyzed by median FeNO scores within FeNO concentration subgroups across the reporting range for the device. The table below presents the whole study population (n=82), but data were also subgrouped by age range: 5 to 17 years (n=37), and ≥ 18 years (n=45). The clinical imprecision was less than 5ppb by mean standard deviation for FeNO values below 50ppb, and %CVs for FeNO values greater than 50ppb were maintained at less than 10%, unless the sample size was small, across all subgroups.
| Age Group | Visit | Median Concentrations | N | Within Subject
Mean SD | 95% CI for SD | Within Subject
Mean CV (%) | 95% CI for CV |
|-----------|--------------------|-----------------------|----|---------------------------|---------------|-------------------------------|----------------|
| All | Visit 1 (Baseline) | 0 to =100 | 18 | 4.37 | 3.28, 6.54 | 3.09% | 2.32%, 4.63% |
| | Visit 2 | 0 to =100 | 1 | 2.41 | | 1.69% | |
Summary of Clinical Precision of FeNO Measurements by Visit
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| Age Group | Visit | Median Concentrations | N | Within Subject
Mean SD | 95% CI for SD | Within Subject
Mean CV (%) | 95% CI for CV |
|-----------|--------------------|-----------------------|----|---------------------------|---------------|-------------------------------|----------------|
| 5 to 17 | Visit 1 (Baseline) | 0 to =100 | 10 | 4.57 | 3.14, 8.34 | 3.31% | 2.28%, 6.05% |
| | Visit 2 | 0 to =100 | 1 | 2.41 | | 1.69% | |
| >=18 | Visit 1 (Baseline) | 0 to =100 | 8 | 4.12 | 2.72, 8.38 | 2.80% | 1.85%, 5.70% |
| | Visit 2 | 0 to =100 | 0 | | | | |
In a third study, Fenom Pro was evaluated to show clinical efficacy; the study was designed to demonstrate that the device can be used successfully to monitor changes in fractional exhaled nitric oxide in uncontrolled asthma patients when therapeutic agents are administered. Specifically, the intent was to show that there is a significant concordance between Fenom Pro and other established asthma-related outcome measures.
A total of 82 subjects (37 five to 17 years of age and 45 aged 18 and older) with uncontrolled asthma participated in a longitudinal study where measurements for FeNO, spirometry, and asthma questionnaires were completed at baseline (Visit 1) and two weeks later (Visit 2) after therapeutic agents were administered. The data demonstrated that significant differences between the two visits were achieved for all three modalities, and therefore concordance between Fenom Pro and the established asthma-related outcome measures.
The results of Passing-Bablok regressions are summarized in the table below for the key asthma condition assessments of FEV1 and ACQ/pACQ that show concordance. Note that two subject records did not have asthma symptom scores available thus study population for the correlations dropped to n=80.
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| Parameter | FeNO vs. FEV1 | FeNO vs. ACQ/pACQ |
|---|---|---|
| N in comparison | 80 | 80 |
| Slope point estimate | -0.0017 | 0.0089 |
| Slope 95% CI | -0.0032 to 0.0000 | 0.0014 - 0.0148 |
| Y-intercept point estimate | 0.0956 | -0.5018 |
| Y-intercept 95% CI | 0.0091 - 0.1250 | -0.7432 to -0.1848 |
| Kendall's Tau point estimate | -0.1599 | 0.1931 |
| Kendall's Tau 95% CI | -0.3003 to -0.0126 | 0.0468 - 0.3312 |
| Kendall's Tau p-value | 0.0370 | 0.0125 |
807.92 (b)(3): Conclusions from Nonclinical and Clinical Data
The conclusions drawn from the analytical and clinical data demonstrate that the device is safe and effective for its intended use.