K Number

Device Name

NIOX MINO MODEL 09-1000

Manufacturer

AEROCRINE AB

Date Cleared

2010-09-02

(141 days)

Product Code

MXA

Regulation Number

862.3080

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 User Manual and by 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 is a small, hand-held, portable system for the non-invasive, online, quantitative measurement of the fractional nitric oxide (NO) concentration in expired human breath (FENO) measured in parts per billion levels (ppb). The device is intended for routine clinical use and is suitable for point of care settings. Measurement of changes in the FENO concentration is used in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of asthma. All results are to be interpreted in conjunction with other clinical and laboratory assessments of the patient's condition. The NIOX MINO unit includes a sampling and gas conditioning system and a man-machine interface (MMI). The user is guided by the built-in touch-screen display through the breathing maneuver by use of the interactive MMI. The valves and pumps of the instrument are automatically controlled to handle the inhaled sample appropriately via the instrument electronics and software program. Filtering of inhaled air eliminates contamination from ambient NO levels. A built-in flow control keeps exhalation standardized at 50 ml/s. Results are processed using dedicated software and are expressed as the Nitric Oxide concentration in parts per billion (ppb). To be able to verify the performance of the device and reliability of measurements, there are built-in system control procedures and a special designed External Quality Control Test Program, to be performed on a daily basis.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K072816

Reference Devices

K072816

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on standard gas analysis technology and software for processing measurements, with no mention of AI or ML algorithms for data interpretation or prediction.

Therapeutic

No
The device measures FENO to evaluate a patient's response to anti-inflammatory therapy, but it does not provide therapy itself. It is a diagnostic/monitoring tool.

Diagnostic

Yes

The device measures fractional NO concentration in expired breath (FENO) to evaluate an asthma patient's response to anti-inflammatory therapy. This measurement provides information that aids in determining the therapeutic effect, distinguishing it as a diagnostic device.

SaMD (Software as a Medical Device)

The device description explicitly states that the NIOX MINO unit includes hardware components such as a sampling and gas conditioning system, valves, pumps, and a touch-screen display, in addition to software.

IVD (In Vitro Diagnostic)

Based on the provided information, the NIOX MINO is not an In Vitro Diagnostic (IVD) device.

Here's why:

IVD Definition: In Vitro Diagnostic devices are used to examine specimens derived from the human body (like blood, urine, tissue) outside of the body to provide information for diagnosis, monitoring, or screening.
NIOX MINO's Function: The NIOX MINO measures Nitric Oxide directly in the patient's exhaled breath. This is a measurement taken from the body, not of a specimen derived from the body and tested externally.
Intended Use: The intended use describes measuring a substance in breath to evaluate a patient's response to therapy. While this information is used in a clinical context, the measurement itself is not performed on an in vitro specimen.

Therefore, the NIOX MINO falls under the category of a medical device that performs a measurement directly on the patient, rather than an IVD device that analyzes a sample outside the body.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for 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 with assurance that such measurements are repeatable and 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 vears 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 User Manual and by 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.

Product codes

MXA

Device Description

Measurement of changes in the FENO concentration is used in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of asthma. All results are to be interpreted in conjunction with other clinical and laboratory assessments of the patient's condition.

The NIOX MINO unit includes a sampling and gas conditioning system and a man-machine interface (MMI). The user is guided by the built-in touch-screen display through the breathing maneuver by use of the interactive MMI. The valves and pumps of the instrument are automatically controlled to handle the inhaled sample appropriately via the instrument electronics and software program. Filtering of inhaled air eliminates contamination from ambient NO levels. A built-in flow control keeps exhalation standardized at 50 ml/s.

Results are processed using dedicated software and are expressed as the Nitric Oxide concentration in parts per billion (ppb).

To be able to verify the performance of the device and reliability of measurements, there are built-in system control procedures and a special designed External Quality Control Test Program, to be performed on a daily basis.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

human breath

Indicated Patient Age Range

children, approximately 7 - 17 years, and adults 18 years and older.

Intended User / Care Setting

physicians, nurses, respiratory therapists and laboratory technicians. The device is intended for routine clinical use and is suitable for point of care settings.

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

Verification of system performance has been performed as a laboratory test, using gas mixtures of NO in N2 of known concentrations.

Clinical validation and method comparison has been performed in a clinical study, named AER-039. This study is a randomized, single-centre study determining the agreement between the NIOX Flex Nitric Oxide Monitoring system and the hand-held NIOX MINO -09 device, using the 10-second exhalation mode.

The primary objective of this study was to determine the degree of agreement between the NIOX Flex Nitric Oxide Monitoring system and the hand-held NIOX MINO -09 device when measuring fractional exhaled nitric oxide using the 10-second exhalation mode and when similar conditions are considered and examinations were made as consistently as possible.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Validation, verification and testing is performed, and based on recommendations in FDA Guidance document for Breath Nitric Oxide Test system, issued July 7, 2003.

Verification of system performance has been performed as a laboratory test, using gas mixtures of NO in N2 of known concentrations.

The results from performed Validation, Verification and Testing conclude that the performance of the modified version of NIOX MINO is within the Technical Specification, initially established for NIOX MINO in application K072816.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Linearity: Squared correlation coefficient r^2 > 0.998 , slope 0.95 – 1.05, intercept ±3 ppb. Determination based on the regression analysis using standard gas reference samples at seven different concentration levels covering the operating measurement range.
Lowest Detection Limit: 5 ppb. Determination by analyzing gas concentrations around and below the detection limit. 5 ppb was the lowest detectable level.
Precision: = 30 ppb. Expressed as one standard deviation for replicate measurements with the same instrument, using a certified gas concentration of Nitric Oxide reference standard.
Accuracy: ± 5 ppb or max 10 %. Expressed as the upper 95% confidence limit, based on absolute differences for concentrations 50 ppb, from certified gas concentration of Nitric Oxide reference standard.
Method comparison: 50 ppb. Expressed as the difference between a NIOX MINO FENO value and the corresponding FENO value measured with NIOX instrument from Aerocrine.

Predicate Device(s)

K072816

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.

Summary

Sundbybergsvagen 9 P.O. Box 1024 SE-171 21 Solna, Sweder Storedor
www.aerocrine.com
orgino 556549-10510 Style=1051610101010000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000

Aerocrine

SPECIAL 510(k) SUMMARY - NIOX MINO, K101034

Doc ID RFD-000165-02 / August 30, 2010

1) Submitter's Identification

Submitter	Aerocrine AB
Address	Sundbybergsvägen 9
PO BOX 1024
SE-171 21 Solna
Sweden
Phone Number	+46 8 629 07 80
Fax Number	+46 8 629 07 81
Establishment Organization number	556549-1056
Establishment registration number	3003113455
Aerocrine Contact Person:	Mats Carlson, VP Development & Technical
Operations
Phone number	+46 8 629 07 83
E-mail address	mats.carlson@aerocrine.com
US Address	Aerocrine Inc
562 Central Avenue
New Providence
New Jersey 07974
Phone Number	212-810-2480
Fax Number	212-656-1723
Establishment registration number	3006173825
Regulatory contact for this submission	Joel Slomoff, Consultant
Phone Number	301 983 1707
Address	9229 Cranford Drive, Potomac, MD 20 854,
USA
E-mail address	rjslomoff@hotmail.com
Summary preparation date:	August 30, 2010

SEP

ﺳﭩﯿﺸ

2) Special 510(k) application for Device

2a) Device information:

Trade name	NIOX MINO®
Common/Generic Device Name	Airway inflammation monitor
Initial 510(k) number	K072816
510(k) number, device modification:	K101034
Classification Name	Breath Nitric Oxide Test System
Device Class	II
Product Code	MXA
Regulation number	21 CFR 862.3080
Medical Specialty	CH, Clinical Chemistry
Owner/Operator	AEROCRINE AB
Owner/Operator number	9057041
Establishment Operations	Specification Developer, Manufacturer

2b) Justification for a Special 510(k):

This application represents a modification to the 510(k) cleared device NIOX MINO, K072816.

Following the FDA guidance document "The New 510(k) paradigm -- alternate approaches to demonstrating substantial equivalence in premarket notifications", from March 20, 1998.

I ) The device for this application represents a modification to the 510(k) cleared device NIOX MINO, K072816.

The Intended Use is identical to the Intended Use for the 510(k) cleared device NIOX MINO, K072816
The fundamental scientific technology is identical to the 510(k) cleared device NIOX MINO, K072816.
The modification is considered appropriate for reliance on results from design control process. 5) Design validation for the change has been /is being performed.
Conformance to Special Control guidance 21 CFR 862.3080 "Breath Nitric Oxide Test system. issued July 7, 2003. (Product Code MXA) is assured.

3) Substantial equivalence is claimed to 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® Nitric Oxide Breath Analyzer Breath Nitric Oxide Test System II MXA 21 CFR 862.3080 CH. Clinical Chemistry AEROCRINE AB 9057041 Specification Developer, Manufacturer K072816

4) Device Description:

Results are processed using dedicated software and are expressed as the Nitric Oxide concentration in parts per billion (ppb).

5) 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 with assurance that such measurements are repeatable and according to guidelines for NO measurement established by the American Thoracic Society.

6) Summary of technology characteristics and performed tests

Based on the feed-back from current customers and the standard practice, some minor design changes are proposed to the NIOX MINO device. The changes are mainly for improvement of Quality Assurance and improved robustness.

The Device operates after identical functionality regarding:

. Man-machine interface for the operator and patient
. Analytical sensor and sampling processing

The proposed modification is a minor control mechanism change related to the Quality Control functionality in NIOX MINO.

Fundamental Scientific Technology

The fundamental scientific technology in NIOX MINO remains unchanged:

. The analytical principle of electrochemical detection remains unchanged.
. The NO sensor design and signal processing remains unchanged.
The principle for sample collection and sample handling inside the instrument remains . unchanged.
. The principle for data presentation remains unchanged
The measurement performance (precision, linearity, accuracy, detection limit) specifications . remain unchanged.

Proposed device modifications are appropriate for reliance on the Design Control process:

Control mechanism modification related to Quality Control procedure:

1. Extended external Quality Control, (negative and positive control every day)
1. Exchangeable NO-scrubber, (for elimination of ambient NO in the patient sample.) and separate zero scrubber (for ambient air filtration for baseline control).

Other minor design changes:

1. The number of tests possible to perform with the instrument is extended from 1500 measurements to 3000 measurements. The instrument life time of 3.5 years remains unchanged. The number of tests and life time for the sensors remain unchanged.
1. Data transfer is changed to USB standard instead of irDA communication
1. Patient data storage, is changed internal memory instead of external smart cards.
1. Monitoring of ambient humidity is included as a parameter in instrument supervision, data is stored in the instrument log file.

Validation, Verification and Testing:

These design modifications, which affects both the mechanical. Hardware and Software design, are considered appropriate for reliance on the results from Aerocrine's internal Design Control process, including performed risk analysis.

Validation, verification and testing is performed, and based on recommendations in FDA Guidance document for Breath Nitric Oxide Test system, issued July 7, 2003.

Verification of system performance has been performed as a laboratory test, using gas mixtures of NO in N2 of known concentrations.

SW validation is performed according to Guidance "General Principles of Software Validation" NIOX MINO software is considered as "Moderate Concern" Software.

Electrical safety and EMC testing according to 60601-1 are performed by a third part accredited test institute, CE Cert GmbH in Germany.

The product labeling / Instructions for use has been updated to reflect the design modifications.

Validation results and conclusion:

Performance Parameter	Specification Tolerance Limits and definition
Linearity	Squared correlation coefficient $r^2 > 0.998$ ,
slope 0.95 – 1.05, intercept ±3 ppb.
Determination based on the regression analysis using standard gas
reference samples at seven different concentration levels covering the
operating measurement range.
Lowest Detection Limit	5 ppb
Determination by analyzing gas concentrations around and below the
detection limit. 5 ppb was the lowest detectable level
Precision	50 ppb, from certified gas concentration of Nitric
Oxide reference standard.
Method comparison:	50 ppb
Expressed as the difference between a NIOX MINO FENO value and the
corresponding FENO value measured with NIOX instrument from
Aerocrine

The performance specification for the new version of NIOX MINO is presented as follows

Performance data typical for temperature range +16 to +30 ℃ Humidity range 20 - 60 % RH, Pressure 1013 hPa

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized caduceus symbol, which is a staff with two snakes coiled around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus symbol. The logo is black and white.

Public Health Service

Aerocrine AB c/o Ms. Johanna Karling Quality Assurance & Regulatory Affairs Director Sundbybergsvagen 9, PO Box 1024 Solna, Sweden SE-17121

Re: K101034

Trade Name: NIOX MINO® Regulation Number: 21 CFR §862.3080 Regulation Name: Breath Nitric Oxide Test System Regulatory Class: Class II Product Codes: MXA Dated: August 2, 2010 Received: August 6, 2010

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

SEP.

2 2010

Dear Ms. Karling:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

Indications for Use

K101034

510(k) Number (if known): K101034

Device Name: NIOX MINO

Indications For Use:

Measurement of FE , by NIOX MINO is a quantitative, non-invasive, simple and safe method to concentration in asthma patients that often occurs after treatment with measure the decrease in FE anti-inflammatory pharmacological therapy, as an indication of the therapeutic effect in patients with elevated FE, levels. NIOX MINO is suitable for children, approximately 7 - 17 years, and adults 18 years and older.

FE, 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.

Prescription Use AND/OR Over-The-Counter Use x (Part 21 CFR 801 Subpart D) (21 CFR 807 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 (OVD)

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

. 510(k) K101034

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