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 antiinflammatory 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 device can connect to the PC via a standard USB cable or wirelessly via Bluetooth.

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

The provided text describes a Special 510(k) summary for the NIOX® VERO Airway Inflammation Monitor (K150233). This submission is specifically for the activation of existing Bluetooth technology on the predicate device (K133898). Therefore, the performance testing focuses on wireless functionality and its impact, not on the core diagnostic capabilities of measuring FeNO. The document states that the core performance characteristics (analytical limits, precision, accuracy, measurement range, linearity) are identical to the predicate device.

Here's an analysis based on the provided text, addressing your points:

1. A table of acceptance criteria and the reported device performance

Since this 510(k) is for activating Bluetooth, the acceptance criteria and performance for the core function (FeNO measurement) are referenced as being identical to the predicate device (K133898). The key performance criteria for the Bluetooth activation itself relate to wireless coexistence and safety.

Acceptance Criteria (from Predicate/Identical)	Reported Device Performance (NIOX VERO)
Analytical limits at low levels (limit of detection): 5 ppb	Identical to predicate: 5 ppb
Precision (for values < 30 ppb): < 3 ppb of measured value	Identical to predicate: < 3 ppb of measured value
Precision (for values ≥ 30 ppb): < 10% of measured value	Identical to predicate: < 10% of measured value
Accuracy: +/- 5 ppb or max 10%	Identical to predicate: +/- 5 ppb or max 10%
Measurement Range: 5 - 300 ppb	Identical to predicate: 5 - 300 ppb
Linearity, reportable range: Squared correlation coefficient r² ≥ 0.998, slope 0.95 - 1.05, intercept ±3ppb	Identical to predicate: Squared correlation coefficient r² ≥ 0.998, slope 0.95 - 1.05, intercept ±3ppb
Wireless Coexistence/Safety: No risks from wireless interference in the clinical setting (as per FDA Radio Frequency Wireless Technology in Medical Devices guidance)	Wireless coexistence testing performed; demonstrated no additional risks from wireless interference. FCC Part 15B testing repeated with Bluetooth active.

2. Sample size used for the test set and the data provenance

The document does not specify a separate "test set" sample size for the Bluetooth activation. It refers to
"Verification and validation testing was previously performed for Bluetooth functionality prior to FDA clearance."
and "FCC Part 15B testing was repeated with the Bluetooth module active in the NIOX VERO."

The data provenance for the wireless testing is implied to be from the manufacturer's internal testing, conducted previously and then repeated for the US market activation. The country of origin for the internal testing is not explicitly stated, but the manufacturer is based in Sweden. Given the nature of Bluetooth standards and FCC regulations, such testing generally follows international or country-specific standards.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable for this type of submission. The testing described for Bluetooth activation does not involve expert-established ground truth in the way a clinical diagnostic study would. The ground truth for electrical and wireless performance is defined by industry standards and regulatory requirements (e.g., FCC regulations).

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable for this type of submission. Adjudication methods are typically used in studies where clinical interpretations or diagnoses are being evaluated by multiple experts.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is a diagnostic tool for measuring FeNO, and the submission concerns the activation of wireless connectivity. It is not an AI-assisted diagnostic tool involving human reader interpretation.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The device's core function (FeNO measurement) is standalone in the sense that it provides a quantitative measurement. The submission for Bluetooth activation itself is a re-validation of wireless functionality, which is a standalone technical performance. The text states:

"Verification and validation were previously performed to demonstrate that the USB cable communications functions are equivalent to the Bluetooth wireless communication operation."

This indicates that equivalence between wired and wireless communication, both standalone technical functions, was established.

7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

For the core FeNO measurement specified as "identical to predicate," the ground truth for analytical performance (accuracy, precision, linearity) typically relies on reference methods or calibrated gas standards. This document doesn't detail how the predicate's ground truth was established, but it would not be based on expert consensus, pathology, or outcomes data.

For the Bluetooth activation, the "ground truth" for wireless coexistence and safety is compliance with regulatory standards and guidelines (e.g., FCC Part 15B, FDA Radio Frequency Wireless Technology in Medical Devices guidance).

8. The sample size for the training set

Not applicable for this type of device and submission. This is not a machine learning or AI-based device that would require training sets.

9. How the ground truth for the training set was established

Not applicable, as no training set is described or relevant for this submission.

Summary

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

February 26, 2015

AEROCRINE AB KATHLEEN RICKARD CHIEF MEDICAL OFFICER RASUNDAVAGEN 18, 8TH FLOOR SOLNA SE-169 67 SE

Re: K150233

Trade/Device Name: NIOX® VERO Airway Inflammation Monitor Regulation Number: 21 CFR 862.3080 Regulation Name: Breath nitric oxide test system Regulatory Class: II Product Code: MXA Dated: January 30, 2015 Received: February 2, 2015

Dear Ms. Rickard:

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,

Katherine Serrano -A

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

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Indications for Use

510(k) Number (if known) K150233

Device Name NIOX® VERO Airway Inflammation Monitor

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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Image /page/3/Picture/0 description: The image shows the word "Aerocrine" in a bold, blue font. The word is the main focus of the image and is positioned horizontally. The background is plain white, which makes the text stand out.

Image /page/3/Picture/1 description: The image contains the logo for NIOX. The logo consists of an orange and red diamond shape with a white diamond in the center, followed by the word "NIOX" in black letters. To the right of the word "NIOX" is the phrase "CHANGING THE FACE OF ASTHMA CONTROL" in smaller, black letters.

SPECIAL 510(k) SUMMARY

The assigned 510(k) number is: K150233

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:	February 24, 2015
510(k) Applicant:	Aerocrine ABRåsundavägen 18, 8th FloorSE-171-21 Solna, SwedenPhone: +46-8-629-0780Fax: +46-8-629-0781
Contact Person:	Susanne ParksGlobal Director Regulatory Affairs & Quality Assurance
Trade Name:	NIOX VERO®
Common Name:	Airway Inflammation Monitor
Classification Name:Regulatory Class:Product Code:CFR Section:	System, Test, Breath Nitric OxideClass IIMXA21 CFR 862.3080
Predicate Device:510(k) Clearance Number:	NIOX VERO® Airway Inflammation MonitorK133898Class II under 21 CFR 862.3080, Product Code MXA
510(k) Applicant:	Aerocrine ABRåsundavägen 18, 8th FloorSE-171-21 Solna, SwedenPhone: +46-8-629-0780Fax: +46-8-629-0781

Device Description

Aerocrine AB, P.O Box 1024, SE-171 21 Solna, Sweden. Visiting address: Råsundavägen 18, 8th floor Phone: +46 8 629 07 80, Fax: +46 8 629 07 81 Orq. no: 556549-1056, VAT no: SE556549105601 www.aerocrine.com

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Image /page/4/Picture/0 description: The image contains the word "Aerocrine" in a bold, blue font. The text is the primary focus of the image and is positioned horizontally. The background is plain and white, which makes the text stand out.

Intended Use/Indications for Use

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 antiinflammatory 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 antiinflammatory 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. VERO User Manual by trained healthcare professionals. NIOX VERO should not be used in critical care, emergency care or in anesthesiology.

Trade Name	NIOX VERO®	NIOX VERO®
510(k) Number	K150233	K133898
Regulatory Class	Class II	Class II
Regulation Number	21 CFR 862.3080	21 CFR 862.3080
Product Code	MXA	MXA
Intended Use	Identical	See above
Analytical limits at low levels, (limit ofdetection)	Identical to predicate	5 ppb
Precision	Identical to predicate	< 3 ppb of measured valuefor values < 30 ppb< 10% of measured valuefor values ≥30 ppb
Accuracy	Identical to predicate	+/- 5 ppb or max 10%
Measurement Range	Identical to predicate	5 - 300 ppb
Linearity, reportable range	Identical to predicate	Squared correlationcoefficient r² ≥ 0.998, slope0.95 - 1.05, intercept ±3ppb
PC Connection	Bluetooth wireless and USB	USB

Technological Characteristics Compared to Predicate

Aerocrine AB, P.O Box 1024, SE-171 21 Solna, Sweden. Visiting address: Råsundavägen 18, 8th floor Phone: +46 8 629 07 80, Fax: +46 8 629 07 81 Org. no: 556549-1056. VAT no: SE556549105601 www.aerocrine.com

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Image /page/5/Picture/1 description: The image shows the logo for NIOX, a company focused on asthma control. The logo features a red diamond shape on the left, followed by the word "NIOX" in black, sans-serif font. To the right of the name, there is a vertical line, followed by the text "CHANGING THE FACE OF ASTHMA CONTROL" in a smaller, sans-serif font.

The scope of this 510(k) application is the activation of existing Bluetooth technology on the predicate device. The Bluetooth module was present in the previously cleared device, but not active. The activation of the module functionality does not impact the existing device measuring functionality or specifications as it acts as a wireless serial connection only and as an alternate to direct connection via USB cable. As shown above the subject device is identical to the predicate except for Bluetooth operation.

The NIOX VERO software and firmware cleared as part of K133898 already contains the Bluetooth functionality and no software or firmware alterations were necessary to implement this change. The factory configuration for US based NIOX VERO products has been altered to implement this change

Performance Testing

The Bluetooth functionality for the NIOX VERO is currently available outside the US market. Verification and validation testing was previously performed for Bluetooth functionality prior to FDA clearance. The activation of Bluetooth for the US market did not require additional verification and validation of the hardware or software since the testing was previously completed and there were no changes in the hardware or software as part of the update to the device.

Risk analysis documentation has been updated to include additional risks from wireless operation. Wireless coexistence testing has been performed to verify that there are no risks present from wireless interference in the clinical setting. FCC Part 15B testing was repeated with the Bluetooth module active in the NIOX VERO.

This testing was performed as per the FDA Radio Frequency Wireless Technology in Medical Devices issued on 13 August 2013. The results of this testing can be found in the body of this Special 510(k) application and demonstrate that Bluetooth operation in the NIOX VERO device does not create additional risks from wireless interference in the intended device use setting.

Conclusions:

The updated NIOX VERO has the same intended use as the predicate device. The device modifications do not affect the device's fundamental scientific technology, clinical performance, hardware as the functionality was previously implemented in the predicate, but not active in the US market

Wireless coexistence testing and risk analyses have demonstrated that any risks from interference have been properly mitigated as necessary to ensure wireless compliance and safety in the NIOX VERO's intended use environment. Verification and validation were previously performed to demonstrate that the USB cable communications functions are equivalent to the Bluetooth wireless communication operation.

The activation of existing Bluetooth functionality coupled with the appropriate wireless coexistence and FCC testing as per the FDA Guidance and previous verification testing demonstrate that the subject device is as safe and effective as the predicate.

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.