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, 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. NIOX MINO should only be used as directed in the NIOX MINO User Manual and the NIOX MINO Quality Control Test User Manual, by trained physicians, nurses, respiratory therapists and laboratory technicians. 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 anaesthesiology.

Device Description

NIOX MINO® Airway Inflammation Monitor is a hand held device intended to measure fractional exhaled nitric oxide in human breath in ppb levels (parts per billion), complying with 21 CFR 862.3080.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the NIOX MINO® device based on the provided text, structured according to your requested points:

Acceptance Criteria and Device Performance for NIOX MINO®

1. Table of Acceptance Criteria and Reported Device Performance

Characteristic	Acceptance Criteria (from text)	Reported Device Performance (NIOX MINO®)
Linearity	N/A (Predicate Device NIOX®: Integral linearity < 2.5 ppb)	Squared correlation coefficient $r^2 ≥ 0.998$
Precision	N/A (Predicate Device NIOX®: Analytical precision < 2.5 ppb of measured value < 50 ppb; < 5 % of measured value > 50 ppb; Clinical precision < 2.5 ppb of measured value < 50 ppb)	Analytical precision: < 3 ppb of measured value < 30 ppb; < 10 % of measured value ≥ 30 ppb (Expressed as one standard deviation for replicate measurements with the same instrument, using a certified gas concentration of Nitric Oxide reference standard.) Clinical precision: < 3 ppb of measured value < 30 ppb (Clinical precision for values ≥ 30 ppb has not been established.)
Accuracy	N/A (Predicate Device NIOX®: Analytical accuracy ± 2.5 ppb of measured value < 50 ppb; ± 5% of measured value > 50 ppb)	Analytical Accuracy: ± 5 ppb or max 15% (Based on mean of absolute differences from certified gas concentration of Nitric Oxide reference standard. (95% CI))
Method	N/A (Predicate Device NIOX®: No direct comparable criterion specified for method comparison with a different device)	± 5 ppb for values < 50 ppb (Expressed as the difference, using one standard deviation, between a NIOX MINO FENO value and the corresponding FENO value measured with NIOX instrument from Aerocrine.)
Equivalence	The overall acceptance criteria are implicitly tied to demonstrating "substantial equivalence" to the predicate device (NIOX® Nitric Oxide Monitoring System, K021133) in terms of intended use and performance characteristics, as stated in the "Device Description" section. This includes laboratory and clinical tests.	"The performance characteristics for NIOX MINO Airway Inflammation Monitor and NIOX Nitric Oxide Monitoring System are substantially equivalent as shown in laboratory and clinical tests." The results from performance testing (linearity, precision, accuracy) "support substantial equivalence between NIOX MINO and NIOX."

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

Test Set Sample Size: The document does not explicitly state the specific sample size (number of patients or measurements) used for the clinical or non-clinical test sets. It mentions "Multi-center clinical studies" and "Extensive performance testing," but no numerical figures are provided for the number of participants or cases.
Data Provenance: The manufacturer, Aerocrine AB, is located in Sweden. The clinical studies were described as "Multi-center clinical studies," suggesting locations potentially beyond Sweden, but specific countries are not mentioned. The studies were designed to "validate the intended use and verify substantial equivalence," which implies a prospective data collection for evaluation of the new device.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

The document does not provide information on the number of experts used or their specific qualifications for establishing ground truth within the context of the clinical studies. The device measures "fractional exhaled nitric oxide in human breath," and the "guidelines for NO measurement established by the American Thoracic Society" are mentioned. Therefore, the ground truth for NO measurements would likely be based on these established protocols, rather than expert consensus on interpreting an image or complex diagnostic output.

4. Adjudication Method for the Test Set

The document does not describe any adjudication method (e.g., 2+1, 3+1, none) for the test set. Given the nature of the device measuring a physiological parameter (FENO), the "ground truth" would generally be derived from direct measurements according to established protocols, not from expert interpretation requiring adjudication.

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

This question is not applicable to this device. The NIOX MINO® is an airway inflammation monitor that measures a biomarker (FENO) directly from breath. It is not an AI-based diagnostic imaging or interpretive aid that would involve "human readers" or "AI assistance" in the typical sense of medical imaging MRMC studies. The device provides a quantitative measurement, not an interpretation that human readers would perform.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This question is not applicable in the context of an AI algorithm. The NIOX MINO® is a standalone device in the sense that it performs the measurement independently. However, it's not an "algorithm only" device; it's a physical monitoring system. The device's performance is inherently its standalone performance, as it takes a measurement and displays a value. The clinical studies evaluated the performance of this device in its intended use.

7. The Type of Ground Truth Used

The ground truth for the device's measurements is the actual concentration of nitric oxide (NO) in human breath, as measured by a highly accurate reference method or standard. The document mentions:

"certified gas concentration of Nitric Oxide reference standard" for analytical precision and accuracy.
"corresponding FENO value measured with NIOX instrument from Aerocrine" for method comparison, implying the predicate device serves as a reference.
Implicitly, the "guidelines for NO measurement established by the American Thoracic Society" define the correct methodology for obtaining FENO values in a clinical setting.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/machine learning model. The NIOX MINO® is a medical device that measures a physiological marker, not a software algorithm that is trained on a dataset. Therefore, the concept of a training set as understood in AI development is not directly applicable here. The device's internal calibration and operating parameters would be established during its design and manufacturing.

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

As explained in point 8, the concept of a "training set" for an AI model is not applicable. The device's accuracy and precision (its "ground truth" performance) are established through testing against certified gas standards and comparison with a predicate device, as detailed in Table 5-1 and the "Non-clinical studies performed" section.

Summary

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K072816

5. 510(k) Summary		Sundbybergsvägen 9PO Box 1024SE-171 21 Solna, Swedenphone +46 8 629 0780fax +46 8 629 0781www.aerocrine.comorg.no 556549-1056VAT No: Reg. Office Stockholm, SE556549105601
Document template QAF-300079-00		Aerocrine
Product:	NIOX MINO®		Structure/module:
Document ID:	DMD-000139	Version:	02	Author	Johanna Karling
Replaces doc:		Reviewed by:
Document status:	Draft	Approved by:	Mats Carlson	Signature:	Date:
Registered copy no:	Unsigned paper copies = uncontrolled	Cancelled by:
Included in File:	TF	DHF	DMR	CFA	CFB Regulatory submission (register copy in file)
List of receivers:	Key words:

Proposed draft

Submitter's Identification

Submitter	Aerocrine AB
Address	Sundbybergsvägen 9PO BOX 1024SE-171 21 SolnaSweden
Phone Number	+46 8 629 07 80
Fax Number	+46 8 629 07 81
Establishment Organization number	556549-1056
Aerocrine Contact Person:	Johanna KarlingQA Director
Phone number	+46 8 629 07 86
E-mail address	johanna.karling@aerocrine.com
US Address	Aerocrine Inc562 Central AvenueNew ProvidenceNew Jersey 07974
Phone Number	212-810-2480
Fax Number	212-656-1723

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Regulatory contact for this submission	Joel Slomoff, Consultant
Phone Number	202-662-4688
Address	Fulbright & Jaworski L.L.P.801 Pennsylvania Avenue, N.WWashington, D.C. 20004-2623
E-mail address	rslomoff@fulbright.com
Summary preparation date:	2007-09-25
Revised:	2008-01-03

Name of the Device

Trade name Common/Generic Device Name Classification Name Device Class Product Code Regulation number Medical Speciality Owner/Operator Owner/Operator number Establishment Operations

Predicate Device

Trade Name of Predicate Device Common/ Generic Device Name Classification Name Device Class Product Code Regulation number Medical Speciality Owner/Operator Owner/Operator number Establishment Operations 510(k) Number

NIOX MINO® Airway inflammation monitor Breath Nitric Oxide Test System II MXA 21 CFR 862.3080 CH, Clinical Chemistry AEROCRINE AB 9057041 Specification Developer, Manufacturer

NIOX® Nitric Oxide Breath Analyzer Breath Nitric Oxide Test System II MXA 21 CFR 862.3080 CH, Clinical Chemistry AEROCRINE AB 9057041 Specification Developer, Manufacturer K021133

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Device Description

NIOX MINO® Airway Inflammation Monitor is a hand held device intended to measure fractional exhaled nitric oxide in human breath in ppb levels (parts per billion), complying with 21 CFR 862.3080.

NIQX MINO Airway Inflammation Monitor is manufactured by Aerocrine AB, Sweden. For NIOX MINO Airway Inflammation Monitor, Aerocrine AB claims substantial equivalence to the predicate device NIOX® Nitric Oxide Monitoring System (K021133).

Figure 1 NIOX MINO® Airway Inflammation Monitor

The intended use for NIOX MINO Airway Inflammation Monitor is the same as the intended use for NIOX, Nitric Oxide Monitoring System. The performance characteristics for NIOX MINO Airway Inflammation Monitor and NIOX Nitric Oxide Monitoring System are substantially equivalent as shown in laboratory and clinical tests.

Intended use

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, 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. NIOX MINO® should only be used as directed in the NIOX User Manual and the NIOX MINO Quality Control Test User Manual, by trained physicians, nurses, respiratory therapists or laboratory technicians. 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 anaesthesiology.

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Technological characteristics

Table 5-1

Characteristic	NIOX MINO®	NIOX®
Device type	Device for regular clinical practice.Point of care.	Device for regular clinical practice.Not portable.
Target population	Suitable for children, 7 - 17 years, and adults 18 years and older.	Suitable for children, 4 - 17 years and adults 18 years and older.
Dimensions and weight	Height 240 mmWidth 130 mmDepth 100 mmWeight 0.8 kg	Height 500 mmWidth 300 mmDepth 400 mmWeight 40 kg
Measurement method	Electrochemical detection	Chemiluminescence detection
Measurement range	5 - 300 ppb	2 - 200 ppb
Detection level (analytical sensitivity)	5 ppb	2 ppb
Linearity	Squared correlation coefficient $r^2 ≥ 0.998$ ,	Integral linearity< 2.5 ppb
	Determination based on the regression analysis using standard gas reference samples at different concentration levels covering the operating measurement range.	Determination based on the regression analysis using standard gas reference samples at different concentration levels covering the operating measurement range.
Precision	Analytical precision:< 3 ppb of measured value < 30 ppb,< 10 % of measured value ≥ 30 ppb.Expressed as one standard deviation for replicate measurements with the same instrument, using a certified gas concentration of Nitric Oxide reference standard.Clinical precision:< 3 ppb of measured value < 30 ppbThe clinical precision for values ≥ 30 ppb has not been established.	Analytical precision:< 2.5 ppb of measured value < 50 ppb< 5 % of measured value > 50 ppbExpressed as one standard deviation for concentrations below 50 ppb and coefficient variation for concentrations above 50 ppb.Clinical precision:< 2.5 ppb of measured value < 50 ppbClinical precision has not been evaluated for FENO values > 50 ppb.
Accuracy	Analytical Accuracy± 5 ppb or max 15 %Based on mean of absolute differences from certified gas concentration of Nitric Oxide reference standard. (95% CI)	Analytical accuracy± 2.5 ppb of measured value < 50 ppb,± 5% of measured value > 50 ppbBased on mean of absolute differences from certified gas concentration of Nitric Oxide reference standard.
Method Comparison	± 5 ppb for values < 50 ppb,Expressed as the difference, using one standard deviation, between a NIOX MINO FENO value and the corresponding FENO value measured with NIOX instrument from Aerocrine.

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Non-clinical studies performed

Extensive performance testing has been performed to support substantial equivalence. Linearity, precision and accuracy has been evaluated according to laboratory standard NCCLS EP9-P The variation between individual instruments during long-time use under various climate conditions has been studied.

The results from the performance testing support substantial equivalence between NIOX MINO and NIOX.

Clinical studies performed

Multi-center clinical studies have been performed to validate the intended use and verify substantial equivalence to the predicate device.

Clinical studies demonstrated that 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 antiinflammatory pharmacological therapy, as an indication of the therapeutic effect in patients with elevated FENO levels. NIOX MINO has been shown to be suitable for children, 7 - 17 years, and adults 18 years and older.

The normal range for nitric oxide in exhaled breath, exhalation flow rates, length of exhalation, differences in levels due to gender, size, and ethnicity and other such aspects are being continuously discussed, for values and statistical details, kindly consult the official Product Labelling.

It has been demonstrated that only one measurement is sufficient in NIOX MINO to obtain reliable results. For details, kindly consult the Users Manual.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird with outstretched wings, rendered in a stylized, flowing design.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Aerocrine AB c/o Mr. Joel Slomoff. Consultant Fulbright & Jaworski LLP 801 Pennsylvania Avenue Washington, DC 20004

MAR - 3 2008

Re: K072816 Trade Name: Niox Mino™M Regulation Number: 21 CFR 862.3080 Regulation Name: Breath nitric oxide test system. Regulatory Class: Class II Product Codes: MXA Dated: February 27, 2008 Received: February 27, 2008

Dear Mr. Slomoff:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known): K072816

Device Name: NIOX MINO®

Indication For Use:

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Carol C. Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K072-816

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.