The INOmax DS delivery system delivers INOmax® (nitric oxide of 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. It uses a specially designed injector module, which enables tracking of the ventilator waveforms and the delivery of a synchronized and proportional dose of NO. It may be used with most ventilators.

The INOmax DS provides continuous integrated monitoring of inspired O2, NO2, and NO, and a comprehensive alarm system.

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

The INOmax DS 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 in the gas flow to a patients breathing circuit. It may also use the INOblender for backup.

The target patient population is controlled by the drug labeling for INOmax and is currently neonates. The primary targeted clinical setting is the Neonatal Intensive Care Unit (NICU) and secondary targeted clinical setting is the transport of neonates.

Device Description

The INOmax DS2 uses a "dual-channel" design to ensure the safe 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 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 alarms. The dual-channel approach to delivery and monitoring permits INOmax delivery independent of monitoring but also allows the monitoring system to shutdown INOmax delivery if it detects a fault in the delivery system such that the NO concentration could become greater than 100 ppm.

AI/ML Overview

The provided submission for the INOmax DS by INO Therapeutics/Ikaria does not contain acceptance criteria or a study that explicitly details device performance against such criteria. Instead, it focuses on demonstrating substantial equivalence to a predicate device (K061901; INOmax DS (Delivery System)) through non-clinical testing and compliance with regulatory guidance.

Here's a breakdown of the information that is available, and what is missing for each point you requested:

A table of acceptance criteria and the reported device performance
- Acceptance Criteria: Not explicitly stated in a quantifiable, pass/fail table format. The submission mentions compliance with "voluntary standards" (Section 9 and 17, not provided) and the "Guidance Document for Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer" (January 24, 2000) FDA-1157. However, the specific performance requirements from these standards are not detailed in the summary.
- Reported Device Performance: The submission states that "The SVRS testing, the summary of which is described in appendix J of this submission, thoroughly tested all requirements of the software, including the NO delivery and gas monitoring performance. The successful completion of these tests demonstrated that the INOmax DS (Version 2) met the performance requirements of the original product and the new requirements of the revised device." However, the actual results of these performance tests (e.g., accuracy of NO delivery within X% of set value, response time for alarms, battery life under specific conditions) are not provided in the summary.
Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size: Not applicable as no clinical studies were performed. For non-clinical (engineering/software) testing, sample sizes are not typically reported in this context, nor is data provenance in terms of country of origin. The testing described is prospective, in the sense that it was conducted specifically for this submission.
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, as no clinical studies requiring expert ground truth were conducted.
Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Not applicable, as no clinical studies requiring adjudication were conducted.
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
- No MRMC study was conducted. This device is a medical gas delivery system, not an AI-assisted diagnostic tool for human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- The "standalone" performance in this context refers to the device's technical specifications and functionality, which were tested via "SVRS testing" and "hardware changes" assessment. The submission claims these tests demonstrated the device met "performance requirements," implying standalone testing was indeed performed, but the specific results are not provided. The device itself operates without human interpretation of its core function (gas delivery).
The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- For the non-clinical tests, the "ground truth" would be the engineering specifications and performance standards outlined in the voluntary standards and FDA guidance document (e.g., a known, precisely measured concentration of NO for testing analyzer accuracy, or a defined electrical load for battery life testing). These specific internal standards are not detailed in the summary.
The sample size for the training set
- Not applicable, as no machine learning/AI model requiring a training set is described for this device.
How the ground truth for the training set was established
- Not applicable, as no machine learning/AI model requiring a training set is described for this device.

Summary of Device Features and Testing Mentioned:

Device: INOmax DS (Delivery System) - delivers INOmax (nitric oxide for inhalation) therapy gas.
Key Design: "Dual-channel" for safe delivery and monitoring (delivery CPU + flow controller + injector module; separate monitor CPU + gas cells for NO, NO2, O2 + user interface).
New Features (for this revision): Patient data storage and additional operational alarms.
Technology Changes: Ergonomic changes for data collection (patient parameters/device usage) and additional notifications/alerts (visual and audible). Infrared communication added for data transfer, and GUI changed for visual notifications.
Non-Clinical Tests:
- Compliance with voluntary standards (Sections 9 and 17).
- Hardware changes (infrared features) assessed; determined not to affect original functions extensively; connected to common power source and serial data link to battery and monitoring processor.
- SVRS (Software Verification and Validation Requirements Specification) testing of all software requirements, including NO delivery and gas monitoring performance.
- Compliance with "Guidance Document for Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer" (January 24, 2000) FDA-1157.
- Conclusion: Verified that additional communication and alarms did not alter safety or effectiveness.
Clinical Studies: None required or conducted to support substantial equivalence.

In conclusion, based on the provided text, the submission focuses on documenting substantial equivalence through compliance with existing standards and software/hardware verification testing, rather than presenting a formal study with explicit acceptance criteria and corresponding performance data as might be expected for novel diagnostic algorithms.

Summary

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INO Therapeutics/Ikaria Premarket Notification

APR 1 5 2010

K093922

INOmax DS

510(k) Summary

In accordance with 21 CFR 807.92 the following summary of information is provided: December 18, 2009 Date: Submitter: INO Therapeutics/Ikaria 2902 Dairy Drive Madison, Wisconsin 53718

Primary Contact Person: Larry Lepley Associate Director, Regulatory Affairs INO Therapeutics/Ikaria T: 608-226-3415 F: 608-226-3402

David Trueblood Secondary Contact Person: Director, Regulatory Affairs INO Therapeutics/Ikaria T: 608-395-3910 F: 608-226-3402

INOmax DS (Delivery System) Device: Trade Name:

Common/Usual Name: Nitric Oxide Administration Apparatus (primary) Nitric Oxide Administration Apparatus, Back-up System Nitric Oxide Analyzer Nitrogen Dioxide Analyzer

Apparatus, Nitric Oxide Delivery, or Apparatus, Nitric Oxide Classification Names: Backup Delivery, Class II - 21 CFR 868.5165 Product Code: MRN (primary), MRQ, MRP, MRQ

K061901; INOmax DS (Delivery System) Predicate Device(s):

Device Description: The INOmax DS2 uses a "dual-channel" design to ensure the safe 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 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 alarms. The dual-channel approach to delivery and monitoring permits INOmax delivery independent of monitoring but also allows the monitoring system to shutdown INOmax delivery if it detects a fault in the delivery system such that the NO

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concentration could become greater than 100 ppm.

Intended Use:

The INOmax DS provides continuous integrated monitoring of inspired O2, NO2, and NO, and a comprehensive alarm system. The INOmax DS incorporates a battery that provides up to 6 hours of uninterrupted NO delivery in the absence of an external power source.

Technology:

All revisions of NOmax DS utilize component technology to deliver Nitric Oxide gas to the patient. The components consist of the Delivery System unit, the blender, a stand/cart and the NO gas tanks. In this revision the INOmax DS technological characteristic of design has changed with the inclusion of patient data storage and additional operation alarms. This modification of design does not affect the intent of INOmax DS in the delivery of NO gas for the target population of neonatal patients. The patient data storage was included for patient administration and the additional alarms were added to aid in the safe administration of the NO gas.

The fundamental scientific technology remains the same in the concept of the INOmax DS. The proposed INOmax DS includes ergonomic changes related to two specific areas of use;

data collection for the collection of patient parameters/device usage
additional notifications/alerts (visual and audible) to alert । the user of operational events.

These additional functions required the INOmax DS to be modified to accommodate the additional components for data

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transfer utilizing Infrared communication and the change in the Graphic User Interface (GUI) for visual notifications.

Determination of Substantial Equivalence:

Summary of Non-Clinical Tests:

The INOmax DS and its applications comply with voluntary standards as detailed in Section 9 and 17 of this premarket submission.

The hardware changes made to the INOmax DS, to implement the INOmax DS infrared features consisted of adding additional hardware to provide infrared communications to an INOmeter mounted on the INOmax DS gas cylinders. The new hardware did not change the original hardware which controlled all the original INOmax DS functions. The additional electrical connections to the original hardware were connections to the common power source and a serial data link connected to the battery and the monitoring processor. Thus, no extensive retesting of the original INOmax DS was deemed necessary.

The SVRS testing, the summary of which is described in appendix J of this submission, thoroughly tested all requirements of the software, including the NO delivery and gas monitoring performance. The successful completion of these tests demonstrated that the INOmax DS (Version 2) met the performance requirements of the original product and the new requirements of the revised device.

The INOmax DS revision complies to "Guidance Document for Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer" (January 24, 2000) FDA-1157

The results of testing verified that the additional communication of patient data through Infrared transmission and additional alarms did not alter the safety or effectiveness of the INOmax DS operation.

Summary of Clinical Tests:

The subject of this premarket submission, INOmax DS, did not require clinical studies to support substantial equivalence.

Conclusion:

INO Therapeutics/Ikaria considers the INOmax DS to be as safe, as effective, and performance is substantially equivalent to the predicate device(s).

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Image /page/3/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 text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized symbol of three human figures, represented by flowing lines, suggesting unity and collaboration.

Public Health Service

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

Mr. Larry Lepley Associate Director, Regulatory Affairs 2902 Dairy Drive Madison, Wisconsin 53718 United States

Re: K093922

Trade/Device Name: INOmax DS Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: II Product Code: MRN, MRO, MRP, MRP, MRQ Dated: March 15, 2010 Received: March 16, 2010

Dear Mr. Larry Lepley:

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.

APR 1 5 2010

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Page 2 - Mr. Lepley

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 go to

http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/Resourcesfor You/Industry/default.htm.

Sincerely yours.

f.r

Anthony D. Watson, B.S., M.S., M.B.A. Division Director Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INO Therapeutics/Ikaria Premarket Notification

INOmax DS

510(k) Number (if known):

INOmax DS Device Name:

Indications for Use:

The INOmax DS provides continuous integrated monitoring of inspired O2, NO2, and NO, and a comprehensive alarm system.

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

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (Part 21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

L. Schult

(Division Sign-Off) Division of Anesthesiology, General Hospital Infection Control, Dental Devices

510(k) Number: K093922

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.”