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 DS provides a constant dose of INOmax (nitric oxide) therapy gas into the inspiratory limb of the ventilator circuit. The INOmax DS 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. INOmax drug is stored as a gas mixture of NO/N2 in an aluminum cylinder at a nominal pressure of 2200 psig. The cylinder is attached to a high pressure regulator which incorporates a pressure gauge that indicates cylinder pressure when the cylinder valve is open. The cylinder regulator is attached via tubing to the INOmax DS using one of the two NO/NO2 quick connect inlets on the back of the machine. The INOmax enters the back of the INOmax DS, passes through a filter, then a safety shutoff valve, which is open under normal operations. An injector module is placed in the ventilator gas flow between the ventilator inspiratory outlet and the humidifier. Based on the ventilator flow, the INOmax cylinder concentration and set INOmax dose, the proportional solenoid delivers INOmax into the ventilator circuit via the injector module. This allows the INOmax DS to deliver a constant dose of INOmax regardless of the ventilator flow pattern or breath rate. A flow sensor inside the INOmax DS also monitors the NO flow out of the machine. A check valve is included prior to the INOmax DS drug outlet to prevent pressure effects from the ventilator breathing circuit interfering with the NO flow sensor reading. The INOmax DS gas monitoring system provides monitored values for inspired NO, NO2, and O2 The sample gas is withdrawn from the breathing circuit and goes through a water trap to remove excess water, a zero valve, a sample pump and finally a sample flow sensor to the gas monitoring cells. The zero valve allows the gas cells to be zeroed (during low calibration) without having to disconnect the sample line from the breathing circuit. The pump and sample flow sensor ensure a constant sample gas flow rate is maintained to the monitoring cells. The gas monitoring cells are electrochemical; they are specific to each gas and provide an electronic signal, which is proportional to the concentration of the gas present. If the delivery system does go into shut down, the INOmax DS has an integrated backup function which provides a fixed flow of INOmax (0.25L/min) into the injector module using a pneumatic on/off switch and a restrictor built into the delivery side of the system. This fixed flow of INOmax will provide 20 ppm of NO when the continuous ventilator gas flow is 10 L/min. The backup is only for short term use until a replacement delivery system can be obtained. An alarm will warn the user if the backup system is turned on while the main delivery system is in use for INOmax delivery.

AI/ML Overview

The provided document describes the INOmax DS (Delivery System), a device for delivering nitric oxide (NO) therapy, primarily to neonates. The document is a 510(k) summary for a premarket notification (K070867). It details the device's characteristics, its similarities to a predicate device, and the testing conducted to ensure its compliance with design specifications and applicable standards.

Here's an analysis of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly present a table of acceptance criteria with corresponding performance metrics in a pass/fail format typical of many medical device studies for software algorithms. Instead, it describes compliance with various standards and design specifications. The performance is primarily characterized by comparing the INOmax DS to its predicate device (INOvent Delivery System) and outlining its features.

However, based on the narrative, we can infer some key performance aspects and their intended or reported capabilities:

Criterion (Inferred from Design/Standards)	Acceptance Criteria (Implied)	Reported Device Performance (INOmax DS)
NO Delivery Accuracy	Constant concentration of NO as set by user, synchronized and proportional to ventilator waveforms.	Achieves constant dose regardless of ventilator flow or breath rate. NO set resolution is 0.1/1/5 ppm depending on range, accuracy is +/-20% indicated or 2 ppm whichever greater.
Integrated Gas Monitoring	Continuous monitoring of inspired O2, NO2, and NO.	Provides continuous integrated monitoring of inspired O2, NO2, and NO. NO range resolution 0-10ppm +/- (20% of reading +0.5ppm).
NO Monitoring Accuracy	Sufficient accuracy for clinical use.	NO accuracy is +/-20% of reading +0.5ppm.
Battery Backup Duration	Sufficient backup power in absence of external source.	Provides up to 6 hours of uninterrupted NO delivery.
Backup NO Delivery Capability	Fixed flow of NO for emergency situations.	Fixed flow of 250 mL/min of NO, providing 20 ppm with 10 L/min oxygen. Also can use INOblender for backup.
Safety - Fault Detection/Shutdown	System can detect faults and shut down NO delivery if concentration exceeds safe limits.	Monitoring system can shut down INOmax delivery if NO concentration could become greater than 100 ppm.
Ventilator Compatibility	Compatibility with most ventilators.	May be used with most ventilators. New ventilators validated.
Compliance with Standards	Device complies with applicable medical device standards.	Designed to comply with FDA Guidance, IEC 60601-1 (and amendments), IEC 60601-1-2, IEC 60601-1-4, IEC 60601-1-8, CGA V-1, ASTM F-1462-93, ASTM F-1054-87.
Risk Analysis Requirements	Device meets risk analysis requirements.	Testing indicated the INOmax DS met its design input specifications, design output specifications and risk analysis requirements.

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

The document refers to "Testing" that indicated the INOmax DS met its design input, output, and risk analysis requirements. It also states "Validation of ventilators" was performed, and "newly validated ventilators have been qualified with the INOmax DS."

Sample Size for Test Set: Not explicitly stated for any specific test. The phrase "Validation of ventilators" implies a test set of ventilators, but the number is not given.
Data Provenance: Not specified. Given the nature of a 510(k) submission in the US, the testing would generally be expected to be conducted under a US-based quality system, but the geographic origin of the specific test data is not detailed.
Retrospective or Prospective: Not specified. Given the nature of device validation, these would typically be prospective tests conducted on the manufactured device.

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)

This information is not applicable to this type of device submission. The INOmax DS is a physical medical device (gas delivery system), not an AI/software algorithm that requires expert interpretation for establishing ground truth in a diagnostic or image-based context. The "ground truth" for this device would be established by physical measurements against engineering specifications and validated standards.

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

This information is not applicable. Adjudication methods like '2+1' or '3+1' are typically used in clinical studies or for establishing ground truth from multiple expert readings in diagnostic imaging or similar fields. For a device like the INOmax DS, performance is verified through objective measurements and engineering standards, not through adjudication of expert opinions.

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 information is not applicable. An MRMC study is designed to evaluate the performance of diagnostic systems (often AI-assisted) by comparing multiple human readers' interpretations of multiple cases. The INOmax DS is a therapeutic gas delivery system, not a diagnostic imaging or AI-based diagnostic tool.

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

This information is not applicable. The INOmax DS is a physical device with integrated hardware and software for gas delivery and monitoring. It is not an "algorithm only" device, nor is its performance typically evaluated in a standalone "algorithm only" context, as it functions as a complete system with human interaction (setting dose, monitoring, etc.).

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

For this device, the "ground truth" is derived from:

Engineering Specifications: The device's performance against its own design input and output specifications.
Physical Measurements: Quantifiable measurements of gas concentration, flow rates, battery life, and alarm functions.
Compliance with Standards: Verification against established industry and regulatory standards (e.g., IEC, ASTM, FDA guidance documents).

8. The sample size for the training set

This information is not applicable. The INOmax DS is not an AI/machine learning device that requires a "training set" in the conventional sense. The device's operation is based on predefined algorithms and control logic, not learned patterns from data.

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

This information is not applicable for the same reasons as in point 8.

Summary

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K070867

: : : : : : :

APR 2 7 2007

Image /page/0/Picture/2 description: The image shows the logo for "INO Therapeutics". The logo is in black and white and features the letters "INO" in a bold, sans-serif font. The "O" in "INO" is larger than the other letters and has the word "Therapeutics" written inside of it. The word "Therapeutics" is in a smaller, sans-serif font.

6 Route173 Clinton, New Jersey 08809 Tel. 908-238-6312 / Fax 908-238-6402

Date Prepared:	March 22, 2007
Contact Person:	Richard K. Bourne, Ph.D., Vice President, Regulatory Affairs
Subject:	510(k) Summary of Safety and Effectiveness Information forINOmax DS. This summary of safety and effectiveness information isbeing submitted in accordance with the requirements of SMDA 1990 and1992 and 21CFR 807.92.
Proprietary Name:	INOmax DS
Common Name(s):	Nitric Oxide Administration Apparatus (primary)Nitric Oxide Administration Apparatus, Back-up SystemNitric Oxide AnalyzerNitrogen Dioxide Analyzer
Classification(s):	Class II - 21CFR868.5165, MRN (primary)Class II - 21CFR868.5165, MROClass II - 21CFR868.2380, MRPClass II - 21CFR868.2385, MRQ
Panel:	Anesthesiology
Predicate Device(s):	INO Therapeutics' INOmax DS (Delivery System) (primary)510 (k) Number K061901Datex-Ohmeda INOvent Delivery System (now GE Healthcare)510(k) Number K974562
Patient Population:	The targeted patient population is neonates. This is derived from theINOmax drug package labeling.
Clinical Setting:	The primary targeted clinical setting is the Neonatal Intensive Care Unit(NICU) and secondary targeted clinical setting is the transport of neonates.This is derived from the INOmax drug package labeling.

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The technology utilized in the INOmax DS is very similar to the Datex-Technology: Ohmeda INOvent Delivery System (now GE Healthcare), with many of the subsystems and components being unchanged.

Specification	INOvent Delivery System	INOmax DS
Indications for Use	Similar to INOmax DS	Except battery backup is 6 hours and provides an integrated backup system for delivering a fixed flow of NO into a constant flow of breathing circuit gas to produce a constant concentration of NO.
Physical Dimensions	Height 215mmWidth 350mmDepth 430mmWeight 21Kg	Height 220mmWidth 350mmDepth 160mmWeight 5.5Kg
Ventilator Compatibility	Similar to INOmax DS	Except 2-60 L/min for inspiratory flow for neonatal and 4-120L/min for adult.
NO Delivery	Similar to INOmax DS	Except NO set resolution is 0.1/1/5 ppm depend on range, accuracy is +/-20% indicated or 2 ppm whichever greater, and NO inlet pressure is 1.7 to 2.3 Bar (25 to 33 psig).
NO Cylinder INOmax™	Same as INOmax DS	Same
Gas Monitoring	Similar to INOmax DS	Except NO range resolution is 0 to 10ppm +/-(20% of reading +0.5ppm), calibration span is daily zero with span at pre-use test if needed, and NO accuracy is +/-20% of reading +0.5ppm.
Injector Module	Same as INOmax DS	Same
NO delivery Shut Off	Same as INOmax DS	Same
Calibration Gas Cylinders	NO Cal gas 40-80 ppm +/- 4%NO₂ Cal gas 10-15 ppm +/- 10%	INOcal calibration gas, INO Therapeutics LLCNO Cal gas 45 ppm +/- 4%NO₂ Cal gas 10 ppm +/- 10%
Electrical Specifications	Similar to INOmax DS	Except no nurse call and battery back-up is 6 hours.
Environmental Specifications	Similar to INOmax DS	Except ambient operation and storage pressure are 57 to 110 kPa (430 to 825 mmHg) and 0.25 L/min when delivered into 10L/min provides 20 ppm, plus INOblender may also be used
NO Back-up Delivery	20 ppm @ 15 L/min.

Material(s) The materials selected were based upon INO Therapeutics' INOmax DS (Delivery System) and Datex-Ohmeda INOvent Delivery System (now GE . Healthcare),

The INOmax DS provides a constant dose of INOmax (nitric oxide) Device Description: therapy gas into the inspiratory limb of the ventilator circuit. The INOmax DS uses a "dual-channel" design to ensure the safe delivery of INOmax.

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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. INOmax drug is stored as a gas mixture of NO/N2 in an aluminum cylinder at a nominal pressure of 2200 psig.

The cylinder is attached to a high pressure regulator which incorporates a pressure gauge that indicates cylinder pressure when the cylinder valve is open. The cylinder regulator is attached via tubing to the INOmax DS using one of the two NO/NO2 quick connect inlets on the back of the machine.

The INOmax enters the back of the INOmax DS, passes through a filter, then a safety shutoff valve, which is open under normal operations.

An injector module is placed in the ventilator gas flow between the ventilator inspiratory outlet and the humidifier. Based on the ventilator flow, the INOmax cylinder concentration and set INOmax dose, the proportional solenoid delivers INOmax into the ventilator circuit via the injector module. This allows the INOmax DS to deliver a constant dose of INOmax regardless of the ventilator flow pattern or breath rate.

A flow sensor inside the INOmax DS also monitors the NO flow out of the machine. A check valve is included prior to the INOmax DS drug outlet to prevent pressure effects from the ventilator breathing circuit interfering with the NO flow sensor reading.

The INOmax DS gas monitoring system provides monitored values for inspired NO, NO2, and O2 The sample gas is withdrawn from the breathing circuit and goes through a water trap to remove excess water, a zero valve, a sample pump and finally a sample flow sensor to the gas monitoring cells. The zero valve allows the gas cells to be zeroed (during low calibration) without having to disconnect the sample line from the breathing circuit. The pump and sample flow sensor ensure a constant sample gas flow rate is maintained to the monitoring cells.

The gas monitoring cells are electrochemical; they are specific to each gas and provide an electronic signal, which is proportional to the concentration of the gas present.

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If the delivery system does go into shut down, the INOmax DS has an integrated backup function which provides a fixed flow of INOmax (0.25L/min) into the injector module using a pneumatic on/off switch and a restrictor built into the delivery side of the system. This fixed flow of INOmax will provide 20 ppm of NO when the continuous ventilator gas flow is 10 L/min. The backup is only for short term use until a replacement delivery system can be obtained. An alarm will warn the user if the backup system is turned on while the main delivery system is in use for INOmax delivery.

The INOmax DS delivery system delivers INOmax® (nitric oxide for Indications for Use: 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 testing indicated the INOmax DS met its design input specifications, Testing: design output specifications and risk analysis requirements. Testing completed included:

1. Validation of ventilators
  The INOmax DS was designed to comply with the applicable portions of Standard(s): the following product standards
FDA Guidance Document for Premarket Notification Submissions 1. for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer (Special Controls).
1. IEC 60601-1, plus amendments: Medical Electrical Equipment

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1. IEC 60601-1-2: EMC/EMI
1. IEC 60601-1-4: Programmable Systems
1. IEC 60601-1-8: Alarms
1. CGA V-1: Medical Cylinder Connections
1. ASTM F-1462-93: Oxygen Analyzers
1. ASTM F-1054-87: Conical Fittings

The ventilators that are the subject of this application are marketed devices cleared through the 510(k) Premarket Notification Process.

The INOmax DS device described in this Notice has the same intended use Conclusions: and indications, technological characteristics, and principles of operation and software applications as the previously cleared predicate device (INOmax DS:K061901). The only difference is that newly validated ventilators have been qualified with the INOmax DS. This difference does not present any new issues of safety or effectiveness. This device is substantially equivalent to the predicate device.

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Image /page/5/Picture/1 description: The image is a black and white logo for the Department of Health and Human Services, USA. The logo features a circular design with the text "DEPARTMENT OF HEALTH AND HUMAN SERVICES, USA" arranged around the perimeter. Inside the circle is a stylized emblem consisting of three abstract human profiles facing to the right, with flowing lines suggesting movement or connection.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

APR 2 7 2007

Richard K. Bourne, Ph.D. Vice President. Regulatory Affairs INO Therapeutics LLC 6 Route 173 Clinton, New Jersey 08809

Re: K070867

Trade/Device Name: INOmax DS (Delivery System) Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: II Product Code: MRN, MRO, MRP and MRQ Dated: March 28, 2007 Received: March 29, 2007

Dear Dr. Bourne:

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 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 - Dr. Bourne

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); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (240) 276-0120. 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 http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Chiu Lin, Ph.D.

Chiu Lin, Ph.D 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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Indications for Use

510(k) Number (if known):

K070867

Device Name: INOmax DS (Delivery System)

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)

Chula Ulla

ton of Anesthesiology, General Hospital,
cuon Control, Dental Devices
(k) Number: K070867

Page 1 of 1

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.”