NIOX VERO® 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 VERO according to guidelines for NO measurement established by the American Thoracic Society.

Measurement of FeNO by NIOX VERO 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 VERO is suitable for children, 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 VERO is intended for prescription use and should only be used as directed in the NIOX VERO User Manual by trained healthcare professionals. NIOX VERO cannot be used with infants or by children approximately under the age of 7, as measurement requires patient cooperation. NIOX VERO should not be used in critical care, emergency care or in anesthesiology.

Device Description

NIOX VERO is a portable system for the non-invasive, quantitative measurement of the fraction of exhaled nitric oxide (NO) in expired human breath (FeNO). NO levels increase during allergic airway inflammation. Measurement of changes in FeNO concentration is used in evaluating a patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments.

The NIOX VERO system is comprised of the NIOX VERO unit with AC adapter, a rechargeable battery, an electrochemical NO sensor, disposable patient filters, and an exchangeable handle containing an internal NO scrubber filter. The NIOX Panel is an optional PC application for operation of the NIOX VERO from a PC and access to electronic medical record systems.

The patient empties their lungs, inhales deeply through the patient filter to total lung capacity and then slowly exhale for 10 seconds. In approximately one minute, the NO concentration is displayed in parts per billion (ppb).

The NIOX VERO unit includes a sampling and gas conditioning system and a man-machine interface (MMI). The instrument controls the inhaled sample appropriately via the electronics and software program. Filtering of inhaled air elimination from ambient NO levels. A built-in flow control keeps exhalation standardized at 50 ml/s so that it is standardized for all patients. The sample enters an electromechanical sensor and interacts with an electrolyte. A chemical reaction takes place where electrons are generated proportional to the number of NO molecules.

Results are processed using dedicated software. In order to verify the device's performance and reliability of measurements, there are built-in system control procedures and a Quality Control procedure to be performed on a daily basis.

AI/ML Overview

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (NIOX MINO predicate)	Reported Device Performance (NIOX VERO)
Analytical limits (LOD)	5 ppb	5 ppb
Precision	< 3 ppb for values < 30 ppb; < 10% for values ≥ 30 ppb	< 3 ppb for values < 30 ppb; < 10% for values ≥ 30 ppb
Accuracy	+/- 5 ppb or max 10%	+/- 5 ppb or max 10%
Measurement Range	5 - 300 ppb	5 - 300 ppb
Linearity	Squared correlation coefficient r² ≥ 0.998, slope 0.95 - 1.05, intercept ±3ppb	Squared correlation coefficient r² ≥ 0.998, slope 0.95 - 1.05, intercept ±3ppb

2. Sample Size Used for the Test Set and Data Provenance

The document mentions "A comparison study was performed between the NIOX MINO and the NIOX VERO which demonstrate substantial equivalence in a clinical setting." However, the specific sample size for this clinical comparison study and the provenance (e.g., country of origin, retrospective or prospective) of the data are not provided in the supplied text.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This information is not provided in the supplied text. The device measures Fractional exhaled Nitric Oxide (FeNO), and the ground truth for such measurements would typically be based on the device's analytical precision and accuracy using certified gas samples, rather than expert consensus on medical images or clinical judgment.

4. Adjudication Method for the Test Set

This information is not applicable to the type of device and study described and is not provided in the supplied text. Adjudication methods like 2+1 or 3+1 are typically used in studies where multiple human readers interpret data (e.g., images) and their interpretations need to be reconciled to establish a ground truth. For a device measuring a quantitative physiological parameter like FeNO, the "ground truth" is established by the accuracy and precision of the measurement itself against known standards.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with AI vs. without AI Assistance

This information is not applicable and not provided in the supplied text. The NIOX VERO is a standalone medical device that measures FeNO. It is not an AI-assisted diagnostic tool that would be used by human readers to interpret complex data. Therefore, an MRMC study and the concept of human readers improving with AI assistance are not relevant to this device.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the performance characteristics (Analytical limits, Precision, Accuracy, Measurement Range, Linearity) listed in the table under "Reported Device Performance (NIOX VERO)" are indicative of standalone performance as they describe the intrinsic measurement capabilities of the device itself. These tests were conducted using "Nitric Oxide gas samples at certified concentrations," which evaluates the device's ability to accurately measure known quantities of NO independently.

7. The Type of Ground Truth Used

The ground truth for the performance testing was established using Nitric Oxide gas samples at certified concentrations. This allows for the direct comparison of the device's readings against a known, accurate reference.

8. The Sample Size for the Training Set

This information is not provided in the supplied text. The document describes a "510(k) premarket notification" for an established medical device type (FeNO measurement systems). While there may be internal development and calibration (training) processes, the FDA submission focuses on showing substantial equivalence through specific performance criteria rather than detailing training set sizes for machine learning models.

9. How the Ground Truth for the Training Set Was Established

This information is not explicitly provided in the supplied text. Similar to the test set, it is highly probable that the ground truth for any internal training or calibration of the device would also involve the use of Nitric Oxide gas samples at certified concentrations to ensure accurate and precise measurements. The document mentions "The sensor stabilization process has been modified. Instead of maintaining the sensor at a constant temperature, there is a compensation algorithm for temperature and humidity correction to the measurement result." This suggests calibration and potentially a training phase where data is collected and used to develop or refine such compensation algorithms, likely against known NO concentrations under varying environmental conditions.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

November 6, 2014

AEROCRINE SUSANNE PARKS, DIRECTOR, RA & OA P. O. BOX 1024 RÅSUNDAVÄGEN 18, 8TH FLOOR SE-171 21 SOLNA, SWEDEN

Re: K133898

Trade/Device Name: NIOX VERO® Regulation Number: 21 CFR 862.3080 Regulation Name: Breath nitric oxide test system Regulatory Class: II Product Code: MXA Dated: September 23, 2014 Received: September 24, 2014

Dear Ms. Susanne Parks:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (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 Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 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 Division of Industry and Consumer Education 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.

Courtney

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

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Indications for Use

510(k) Number (if known) K133898

Device Name NIOX VERO

Indications for Use (Describe)

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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Råsundavägen 18, 8th floor P.O. Box 1024 SE-171 21 Solna, Sweden phone +46 8 629 0780 fax +46 8 629 0781 www.aerocrine.com org.no 56549-1056 VAT No: Reg. Office Stockholm, SE556549105601

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TRADITIONAL 510(k) SUMMARY

The assigned 510(k) number is: K133898

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SDMA 1990 and 21 CFR 807.92.

Preparation Date:	November 4, 2014
510(k) Applicant:	Aerocrine ABRåsundavägen 18, 8th FloorSE-171-21 Solna, SwedenPhone: +46-8-629-0780Fax: +46-8-629-0781
Contact Person:	Susanne ParksDirector Regulatory Affairs & Quality Assurance
Trade Name:Common Name:Classification Name:Regulatory Class:Product Code:CFR Section:	NIOX VERO®Airway Inflammation MonitorSystem, Test, Breath Nitric OxideClass IIMXA21 CFR 862.3080
Predicate Device:510(k) Clearance Number:510(k) Applicant:	NIOX MINO® Airway Inflammation MonitorK101034Class II under 21 CFR 862.3080, Product Code MXAAerocrine ABRåsundavägen 18, 8th FloorSE-171-21 Solna, SwedenPhone: +46-8-629-0780Fax: +46-8-629-0781

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Device Description

Intended Use/Indications for Use

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Technological Characteristics Compared to Predicate

Similarities

1. Analytical principle of electrochemical detection
1. NO sensor design and signal processing
The principle for sample collection and sample handling inside the instrument 3.
1. Format of the measurement result in ppb
న్. Process of patient sample collection method
The Quality Control procedure 6.
1. The measurement performance specifications ( linearity, accuracy, precision, detection limit)
1. Elimination of ambient NO in patient inhalation and in sampling for baseline control
1. Use of a touchscreen to navigate the device and display a visual incentive for the user to follow.
1. Portable devices
Communication via USB with a PC 11.
1. Internal measurement result storage.
1. The NIOX Panel is a software accessory used with both NIOX MINO and NIOX VERO.
1. Measurements are in accordance with ATS guidelines

Differences

1. The device design was updated:
- The touch screen is larger and in color in the NIOX VERO for ease of use. a.
- The NIOX VERO can operate from battery power. b.
- The patient filter attaches to a handle. This allows the patient to directly view the c. screen which enhances the device to aid the patient in generating a breath sample. The NO scrubber is now located in this handle which will be disposed of after the NO scrubber has expired.
- d. Buffer chamber capacity is smaller.
- e. Flow regulator is now electromechanical.
1. The instrument lifetime was extended to 5.5 years or 15,000 measurements.
The sensor stabilization process has been modified. Instead of maintaining the sensor at 3) a constant temperature, there is a compensation algorithm for temperature and humidity correction to the measurement result.

PERFORMANCE TESTING

Performance testing was conducted to demonstrate substantial equivalence between the NIOX VERO and the NIOX MINO (predicate device).

1. The NIOX VERO conforms to the same electrical safety and EMC performance standards as the predicate device, EN/IEC 60601-1 2nd edition (1988), 60601-1-2:2000).
1. The biocompatibility of the filter was assessed to the same performance standards as the predicate (ISO 10993-1:2003). Cytotoxicity, Sensitization, and Irritation/Intracutaneous reactivity tests were performed. All data indicated the patient filter was safe for use.
1. Software validation is performed according to FDA Guidance: General Principals of Software Validation, Final Guidance for Industry and Staff issued Jan 11, 2002. The NIOX VERO software is considered to be "Moderate Concern" software. IEC 62304 Medical Device Software-Software life Cycle Processes 2006-05 was also utilized.

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Software verification and validation shows the device software and NIOX Panel meets design inputs requirements and user needs. The usability of the NIOX VERO has been validated.

1. Stability testing was performed on the device and the sensor.
1. A comparison study was performed between the NIOX MINO and the NIOX VERO which demonstrate substantial equivalence in a clinical setting.
1. Testing with potential interferents was performed.
1. Specific performance characteristics were developed for the NIOX VERO using Nitric Oxide gas samples at certified concentrations. The following testing was performed and results are compared to NIOX MINO.

	NIOX MINO (predicate)	NIOX VERO
Analytical limits at low levels,(limit of detection)	5 ppb	5 ppb
Precision	< 3 ppb of measured value forvalues < 30 ppb< 10% of measured value forvalues ≥30 ppb	< 3 ppb of measured value forvalues < 30 ppb< 10% of measured value forvalues ≥30 ppb
Accuracy	+/- 5 ppb or max 10%	+/- 5 ppb or max 10%
Measurement Range	5 - 300 ppb	5 - 300 ppb
Linearity, reportable range	Squared correlationcoefficient r² ≥ 0.998, slope0.95 - 1.05, intercept ±3ppb	Squared correlationcoefficient r² ≥ 0.998, slope0.95 - 1.05, intercept ±3ppb

Conclusions:

The NIOX VERO has the same intended use as the predicate device, the NIOX MINO. The minor changes to the indications do not alter the intended diagnostic effect and do not impact the safety and effectiveness of the device modifications do not affect the device's fundamental scientific technology. Performance testing demonstrates the NIOX VERO is substantially equivalent in technological characteristics and does not raise new questions of safety and effectiveness. Furthermore, the performance testing confirms that the NIOX VERO is as least as safe and effective as the NIOX MINO (predicate) device.

Regulation Number and Section

§ 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.