The INOmax DSIR® Plus MRI delivery system is indicated for delivery of INOMAX® (nitric oxide for inhalation) therapy gas into the inspiratory limb of the patient breathing circuit in a way that provides a constant on of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath. The INOmax DSIR® Plus MRI is indicated for use only with MR Conditional ventilators validated to be compatible, as identified in the device labeling.

The INOmax DSIR® Plus MRI is indicated for continuous integrated monitoring of inspired 02, NO2, and NO.

The INOmax DSIR® Plus MRI is considered MR Conditional with the use of 1.5 Tesla static magnetic field scanners ONLY in areas where the field strength is less than 100 gauss.

The target patient population is controlled by the drug labeling for INOMAX® and is currently neonates. The primary targeted clinical setting is a clinical 1.5 Tesla and 3.0 Tesla diagnostic imaging environment.

Device Description

The INOmax DSIR® uses a "dual-channel" design to provide delivery of INOMAX®. The first channel has the delivery CPU, the flow controller and the injector module to ensure the accurate delivery of NO. The specially designed injector module enables tracking of the ventilator waveforms and the delivery of a synchronized and proportional dose of NO. The second channel is the monitoring system, which includes a separate monitor CPU, the gas cells (NO, NO2, and O2 cells) and the user interface including the display and a comprehensive alarm system. The dual-channel approach to delivery and monitoring permits INOMAX® delivery independent of monitoring but also allows the monitoring system to shut down INOMAX® delivery if the monitored NO concentration exceeds 100 ppm for 12 consecutive seconds. The delivery system can also shut down delivery if it detects certain serious problems with the monitoring system.

The INOmax DSIR Plus MRI incorporates a battery that provides up to 6 hours of uninterrupted NO delivery in the absence of an external power source.

The INOmax DSIR Plus MRI includes a backup NO delivery capability that provides a fixed flow of 250 mL/min of NO, which along with user supplied 10 L/min of oxygen, provides 20 ppm of NO to a patient breathing circuit. The INOblender® can also be used for backup.

AI/ML Overview

The provided document is a 510(k) summary for the INOmax DSIR® Plus MRI, a nitric oxide administration apparatus. It outlines the device description, intended use, technological characteristics, and a comparison to a predicate device, as well as a summary of nonclinical tests performed.

However, the document does not contain the specific information requested about acceptance criteria and a study proving the device meets those criteria in the context of typical AI/ML medical device submission requirements.

Here's why and what information can be extracted or deduced:

This document describes a hardware medical device, not an AI/ML powered software or diagnostic device. Therefore, the concepts of "acceptance criteria" and "device performance" as typically discussed for AI/ML models (e.g., sensitivity, specificity, AUC) are not directly applicable in the same way. The "performance" here refers to the device's functional operation meeting engineering specifications.

Let's address each point based on the available information:

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

Acceptance Criteria (Deduced from testing goals): The document implies acceptance criteria are related to the device's functional performance:
- O2 dilution: The device should not unacceptably dilute oxygen concentration.
- Effect on delivered pressures: The device should not adversely affect ventilator delivered pressures.
- INOmax DSIR® delivery accuracy: The device should accurately deliver Nitric Oxide.
- NO2 generation: The device should not generate unacceptable levels of Nitrogen Dioxide.
- MRI Compatibility: Device classified as MR Conditional for 1.5 Tesla and 3.0 Tesla static magnetic field scanners in areas where field strength is less than 100 gauss (via ASTM standards and other tests).
- Electrical Safety & EMC: Conformity to IEC 60601-1 and IEC 60601-1-2.
- Alarm Systems: Conformity to IEC 60601-1-8.
- Software Functionality: Software version 3.1.2 meets specified requirements.
- Usability: Meets human factors engineering requirements (ANSI/AAMI HE75).
- Backup delivery: Provides fixed flow of 250 mL/min of NO.
Reported Device Performance:
- "The INOmax DSIR® performed within published specifications when used with each of the ventilators in both primary and backup delivery."
- "The INOmax DSIR® Plus MRI meets its system level requirements and that the new/modified features function as specified."
- Compliance with specific FDA recognized consensus standards (IEC 60601-1, IEC 60601-1-2, IEC 60601-1-8, ASTM F2052-06, ASTM F2119-07, ASTM F2503-13).

Table of (Deduced) Acceptance Criteria and Performance:

Acceptance Criteria (Inferred)	Reported Device Performance
Functional Safety & Compatibility:
O2 dilution acceptable	Performed within published specifications when used with ventilators.
No adverse effect on delivered pressures	Performed within published specifications when used with ventilators.
INOmax DSIR® delivery accuracy	Performed within published specifications when used with ventilators; measured values on the INOmax DSIR® were recorded and anomalies noted.
Acceptable NO2 generation	Performed within published specifications when used with ventilators.
MR Conditional for 1.5T/3.0T static fields (<100 gauss)	Classification as MR Conditional with the use of 1.5 Tesla and 3.0 Tesla static magnetic field scanners ONLY in areas where the field strength is less than 100 gauss. Compliance with ASTM F2052-06, ASTM F2119-07, ASTM F2503-13. Cart-mounted Gauss Alarms (100 Gauss) included.
Electrical Safety & Quality:
Electrical safety (Basic Safety and Essential Performance)	Conformity to IEC 60601-1:2005.
Electromagnetic Compatibility (EMC)	Conformity to IEC 60601-1-2:2007.
Alarm System performance	Conformity to IEC 60601-1-8:2006.
Software meets requirements and functions as specified	Verification confirmed the INOmax DSIR® Plus MRI meets its system level requirements and that new/modified features function as specified.
Usability (Human Factors Engineering)	Formative usability study conducted per ANSI/AAMI HE75. Meets system level requirements.
Backup NO delivery capability (250 mL/min NO, 20 ppm with O2)	Device includes a backup NO delivery capability providing a fixed flow of 250 mL/min of NO; performed within specifications in backup delivery.
6 hours uninterrupted NO delivery on battery	Integrates a battery that provides up to 6 hours of uninterrupted NO delivery. (Performance implies this function was confirmed).

Regarding AI/ML specific questions (2-9), the following applies since this is not an AI/ML device:

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Not applicable as this is a hardware device. Testing involved physical device performance and compatibility with other medical equipment, not analysis of a data set. The document mentions "Five INOmax DSIR® settings were used [0 (baseline), 5. 10. 20. 40. and 80 ppm] for each mode of ventilation, as well as the Backup mode." This describes test parameters, not a patient sample size or data provenance.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable. Ground truth for a hardware device's functional performance is established through engineering and medical device standards (e.g., accuracy of gas delivery, safety limits). Not expert interpretation of data.

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

Not applicable. This concept pertains to resolving discrepancies in expert labeling or diagnoses for AI/ML ground truth.

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 is not an AI/ML device intended to interpret data for human readers.

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

Not applicable. This is a standalone medical device, but not in the context of an algorithm's performance.

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

For a hardware device, "ground truth" relates to its adherence to established engineering specifications, safety standards, and functional requirements. For example, the ground truth for "NO delivery accuracy" would be calibration standards and expected physical/chemical properties.

8. The sample size for the training set

Not applicable. This device does not have a "training set" in the context of AI/ML.

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

Not applicable. This device does not have a "training set" for AI/ML.

Summary

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

July 10, 2015

INO Therapeutics/Ikaria Mr. Robert Bovy Associate Director, Regulatory Affairs 6603 Femrite Drive Madison, WI 53718

Re: K143213

Trade/Device Name: INOmax DSIR® Plus MRI Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: II Product Code: MRN, MRO, MRP, MRQ Dated: June 3, 2015 Received: June 4, 2015

Dear Mr. Bovy:

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.

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Page 2 - Mr. Bovy

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 Part 801); 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree 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" (21CFR 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 Small Manufacturers, International and Consumer Assistance 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,

Teiashri Purohit-Sheth, M.D.

Tejashri Purohit-Sheth, M.D. Clinical Deputy Director DAGRID/ODE/CDRH FOR

Erin I. Keith, M.S. Division Director Division of Anesthesiology, General Hospital, Respiratory, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K143213

Device Name INOmax DSIR Plus MRI

Indications for Use (Describe)

The INOmax DSIR® Plus MRI is indicated for continuous integrated monitoring of inspired 02, NO2, and NO.

The INOmax DSIR® Plus MRI is considered MR Conditional with the use of 1.5 Tesla static magnetic field scanners ONLY in areas where the field strength is less than 100 gauss.

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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5. 510(K) SUMMARY

510(k) Summary

In accordance with 21 CFR 807.92 the following summary of information is provided:

Submitter Information

Date:	July 10, 2015
Company:	INO Therapeutics doing business as Ikaria6603 Femrite DriveMadison, Wisconsin 53718
Contact Person:	Robert Bovy
	Associate Director, Device Regulatory Affairs
Email:	Robert.Bovy@Ikaria.com
Telephone:	608-226-3450
FAX:	608-223-0804
Secondary Contact Person:	David Trueblood
Email:	David.Trueblood@Ikaria.com
Telephone:	608-395-3910

ldentification of the Device

Device Name:	INOmax DSIR® Plus MRI
Common Name:	Nitric Oxide Administration Apparatus (primary)Nitric Oxide Administration Apparatus, Back-up SystemNitric Oxide AnalyzerNitrogen Dioxide Analyzer
Classification Name:	Apparatus, Nitric Oxide Delivery, or Apparatus, NitricOxide Backup Delivery
Device Classification:	Class II - 21 CFR 868.5165
Product Code:	MRN (Primary), MRO, MRP, MRQ
Predicate Device(s)	K131686

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Description of Device

The INOmax DSIR Plus MRI incorporates a battery that provides up to 6 hours of uninterrupted NO delivery in the absence of an external power source.

Intended Use

The INOmax DSIR® Plus MRI delivery system is indicated for delivery of INOMAX® (nitric oxide for inhalation) therapy gas into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath. The INOmax DSIR® Plus MRI is indicated for use only with MR Conditional ventilators validated to be compatible, as identified in the device labeling.

The INOmax DSIR® Plus MRI is indicated for continuous integrated monitoring of inspired O2, NO2, and NO.

The INOmax DSIR® Plus MRI is considered MR Conditional with the use of 1.5 Tesla and 3.0 Tesla static magnetic field scanners ONLY in areas where the field strength is less than 100 gauss.

Technological Characteristics

All revisions of INOmax DSIR® utilize component technology to deliver Nitric Oxide gas to the patient. The components consist of the Delivery System unit, the INOblender®, a stand/cart and the NO gas tanks. In this revision of the INOmax DSIR®, the cart hardware, the NO delivery cable and tubing, the gas sampling tubing, the software and the labeling have been updated.

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Determination of Substantial Equivalence

The modifications to INOmax DSIR® for the INOmax DSIR® Plus MRI device included hardware modifications to the cart, an update of the software to version 3.1.2 and modified labeling. The INOmax DSIR® Plus MRI has the same intended therapeutic effect and patient population as the cleared INOmax DSIR® predicate device. All features are the same except those described in the table below.

Feature /Specification	INOmax DSIR® - K131686	INOmax DSIR® Plus MRI with fourrespiratory care devices
Indicated UseEnvironment	The device is not classified as MRConditionalThe primary targeted clinical settingis the Neonatal Intensive Care Unit(NICU) and secondary targetedclinical setting is the transport ofneonates	The device is classified as MRConditional with the use of 1.5 Teslaand 3.0 Tesla static magnetic fieldscannersThe primary targeted clinical settingis a clinical 1.5 Tesla and 3.0 Tesladiagnostic imaging environment
Cart CasterHardware	(4) manually locking casters	(2) automatically locking casterswith disengagement lever on carthandle
Cart-MountedGauss Alarms	None	(2) GaussAlert model 9957-A-01828-B (100 Gauss)
User ConvenienceFeatures	Wizards are available on the devicedisplay for pre-use checkout, gascell calibration, use of backup NOdelivery mode and troubleshootingof alarms	These same wizards are availablewith the addition of a wizard fordevice setup in the MRI suite
Labeling forcompatibility withrespiratory caredevices	A variety of transport, neonatal,adult/pediatric, high frequency andanesthesia ventilators, nasal CPAPand nasal high flow cannulas	Compatible respiratory care devicesinclude:Bio-Med MVP-10/MRINasal CannulaMaquet Servo-i MR EnvironmentOptionPulmonetics LTV Series 1200 MRConditional

Comparison to Predicate Device

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Summary of Nonclinical Tests

The following quality assurance measures were applied to the modification of the system:

. Risk analysis
Formative usability study ●
Requirements reviews
. Design reviews
Testing on unit level (module verification)
Integration testing (system verification) ●
. Performance testing (verification)

Support for the substantial equivalence of the INOmax DSIR® Plus MRI was provided as a result of risk management and testing which included electrical safety, performance and software tests. This testing includes conformity to the FDA recognized consensus standards and voluntary standards as follows:

. IEC 60601-1:2005 - Medical electrical equipment - Part 1: General requirements for basic safety and essential performance
. IEC 60601-1-2:2007 - General requirements for basic safety and essential performance -Collateral standard: Electromagnetic compatibility - Requirements and tests
. IEC 60601-1-8:2006 - General requirements for basic safety and essential performance -Collateral Standard: General requirements, tests and guidance for alarm systems in medical electrical equipment and medical electrical systems
. ASTM F2052-06 - Standard Test Method for Measurement of Magnetically Induced Displacement Force on Medical Devices in the Magnetic Resonance Environment
. ASTM F2119-07 – Standard Test Method for Evaluation of MR Image Artifacts from Passive Implants
. ASTM F2503-13 - Standard Practice for Marking Medical Devices and Other Items for Safety in the Magnetic Resonance Environment

A formative usability study was conducted per ANSI/AAMI HE75 Human Factors Engineering, Design of Medical Devices, to aid in the development of hardware and software requirements and verification confirmed the INOmax DSIR® Plus MRI meets its system level requirements and that the new/modified features function as specified.

To confirm compatibility with the new respiratory care devices were set up and calibrated according to the manufacturer's recommendations and tested using the settings established for each respiratory care device test. The INOmax DSIR® was set up and calibrated according to the manufacturer's recommendations.

Five INOmax DSIR® settings were used [0 (baseline), 5. 10. 20. 40. and 80 ppm] for each mode of ventilation, as well as the Backup mode.

The measured values on the INOmax DSIR® were also recorded along with any anomalies found.

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The testing concluded four requirements necessary for the INOmax DSIR® and the four respiratory care devices to be compatible:

O2 dilution ●
. Effect on delivered pressures
INOmax DSIR® delivery accuracy .
. NO2 generation

Testing Conclusion:

The INOmax DSIR® performed within published specifications when used with each of the ventilators in both primary and backup delivery.

Summary of Clinical Tests

The subject of this premarket submission, INOmax DSIR® Plus MRI, did not require clinical studies to support substantial equivalence.

Conclusion

INO Therapeutics/Ikaria considers the INOmax DSIR® Plus MRI to be as safe and as effective as the predicate device, with performance substantially equivalent to the predicate device.

Regulation Number and Section

§ 868.5165 Nitric oxide administration apparatus.

(a)
Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to be used in conjunction with a ventilator or other breathing gas administration system.(b)
Classification. Class II. The special control for this device is FDA's “Guidance Document for Premarket Notification Submissions for Nitric Oxide Administration Apparatus, Nitric Oxide Analyzer, and Nitrogen Dioxide Analyzer.”