INOMAX DS (DELIVERY SYSTEM), MODEL 10003 by INO THERAPEUTICS

The INOmax DS delivery system delivers 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. 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 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 Limin. 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 is a 510(k) summary for the INOmax DS (Delivery System), indicating its substantial equivalence to previously cleared predicate devices. It describes the device's technical specifications and intended use, but it does not contain information about a study that establishes acceptance criteria through performance metrics like sensitivity, specificity, or accuracy, nor does it detail a study involving human readers or expert consensus for ground truth.

Instead, the document focuses on demonstrating that the INOmax DS meets various engineering and safety standards, and that its performance is comparable to predicate devices. The "acceptance criteria" here are primarily framed as compliance with design specifications and relevant medical device standards.

Here's an attempt to extract the requested information based on the provided text, recognizing that much of it is not explicitly present for a typical AI/diagnostic device study.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the design input and output specifications, and compliance with various standards. The "performance" is described in terms of the device's functional capabilities and its similarity to predicate devices.

Acceptance Criterion (Implied)	Reported Device Performance
Nitric Oxide (NO) Delivery Accuracy	NO set resolution: 0.1/1/5 ppm depending on range. Accuracy: +/- 20% indicated or 2 ppm, whichever is greater. NO inlet pressure: 1.7 to 2.3 Bar (25 to 33 psig).
Backup NO Delivery Functionality	Provides a fixed flow of 0.25 L/min of NO. When delivered into 10 L/min of continuous ventilator gas flow (user-supplied 10 L/min O2), provides 20 ppm of NO. Integrated backup function with pneumatic on/off switch and restrictor.
Gas Monitoring (NO)	Range resolution: 0 to 10 ppm +/- (20% of reading + 0.5 ppm). Accuracy: +/- 20% of reading + 0.5 ppm. Calibration: Daily zero with span at pre-use test if needed.
Gas Monitoring (NO2)	Monitored values for inspired NO2 provided. (Specific accuracy/range not detailed beyond general "gas monitoring" similar to predicate).
Gas Monitoring (O2)	Monitored values for inspired O2 provided. (Specific accuracy/range not detailed beyond general "gas monitoring" similar to predicate).
Ventilator Compatibility	Compatible with most ventilators. Inspiratory flow range: 2-60 L/min for neonatal, 4-120 L/min for adult (differs from predicate). New ventilators "qualified" and "validated."
Battery Backup Duration	Provides up to 6 hours of uninterrupted NO delivery in the absence of an external power source.
Safety Shutoff (High NO Concentration)	Monitoring system can shut down INOmax delivery if it detects a fault where NO concentration could become greater than 100 ppm.
Compliance with Medical Electrical Equipment Standards	Designed to comply with IEC 60601-1, IEC 60601-1-2 (EMC/EMI), IEC 60601-1-4 (Programmable Systems), IEC 60601-1-8 (Alarms).
Compliance with Gas-Related Standards	Designed to comply with CGA V-1 (Medical Cylinder Connections), ASTM F-1462-93 (Oxygen Analyzers), ASTM F-1054-87 (Conical Fittings).
Compliance with FDA Guidance for Nitric Oxide Delivery Devices	Designed to comply with FDA Guidance Document for Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer (Special Controls).
Physical Dimensions	Height 220mm, Width 350mm, Depth 160mm, Weight 5.5Kg (significantly smaller/lighter than predicate)
Materials Selection	Materials based on INOmax DS Material(s) and Datex-Ohmeda INOvent Delivery System.
Environmental Specifications	Ambient operation and storage pressure: 57 to 110 kPa (430 to 825 mmHg) (differs from predicate). Similar to INOmax DS for other environmental aspects.
Calibration Gas Cylinders	Uses INOcal calibration gas (INO Therapeutics LLC). NO Cal gas 45 ppm +/- 4%. NO₂ Cal gas 10 ppm +/- 10%.

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

The document states "Testing indicated the INOmax DS met its design input specifications, design output specifications and risk analysis requirements. Testing completed included: Validation of ventilators." However, it does not specify:

The exact sample size for the ventilator validation or other electrical/mechanical tests.
The data provenance (e.g., country of origin, retrospective/prospective). This type of device's "testing" is typically bench testing and laboratory validation, not clinical data collection on patients in the way a diagnostic AI would be.

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

This information is not provided in the document. The device is an electro-mechanical gas delivery system, not a diagnostic tool requiring expert interpretation of images or other clinical data for "ground truth" establishment in the typical sense of AI/medical imaging studies. Ground truth here would be established by reference instruments and engineering standards.

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

This information is not provided and is not applicable for this type of device validation. Adjudication methods are typically used in clinical studies comparing human interpretations.

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

No, an MRMC study was not done. This document describes a device for delivering therapeutic gas, not an AI-powered diagnostic tool that assists human readers.

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

Yes, implicitly. The device is a "standalone" system in that it performs its functions (gas delivery, monitoring) automatically based on user settings and its internal algorithms. Its performance is evaluated against engineering specifications and predicate devices, not typically in a human-in-the-loop context for a diagnostic output. The "testing" mentioned ("Validation of ventilators") would inherently be a standalone evaluation of the device's ability to interface and deliver gas with various ventilators.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

For this type of device, the "ground truth" for performance evaluations would be:

Reference measurements: From calibrated scientific instruments for gas concentrations (NO, NO2, O2), flow rates, pressure, etc.
Engineering specifications: The device is designed to meet specific numerical parameters, and testing validates these parameters using metrology.
Standard compliance: Adherence to national and international medical device standards (e.g., IEC 60601 series, ASTM, CGA).
Predicate device performance: Functional equivalence to prior cleared devices serves as a benchmark.

8. The Sample Size for the Training Set

This information is not applicable and not provided. This is not an AI/machine learning device that requires a "training set." Its functionality is based on established physical principles and control algorithms, not learned patterns from data.

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

This information is not applicable as there is no training set for this device.

Summary

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page 1 of 5 K680484

Image /page/0/Picture/1 description: The image shows the logo for "INC Therapeutics". The letters "INC" are in bold, black font, with the "C" partially surrounding the word "Therapeutics". The word "Therapeutics" is in a smaller, less bold font than "INC".

AUG - 6 2008

2820 Walton Commons West Madison, WI 53718 USA Tel. 608-395-3900 / Fax. 608-395-3905

Date Prepared:	February 2008
Subject:	510(k) Summary of Safety and Effectiveness Information for the INOmaxDS. This summary of safety and effectiveness information is beingsubmitted in accordance with the requirements of SMDA 1990 and 1992and 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	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 K061901INO Therapeutics' INOmax DS (Delivery System)510(k) Number K070867INO Therapeutics' INOmax DS (Delivery System)510(k) Number K071516Datex-Ohmeda INOvent Delivery System (now GE Healthcare)510(k) Number K974562
Contact Person:	Frederick Montgomery, Vice President, Medical Devices
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 neonatesis 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 providesan integrated backup system for delivering afixed flow of NO into a constant flow ofbreathing circuit gas to produce a constantconcentration 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 forneonatal and 4-120 L/min for adult.
NO Delivery	Similar to INOmax DS	Except NO set resolution is 0.1/1/5 ppm dependon range, accuracy is +/- 20% indicated or 2ppm whichever greater, and NO inlet pressure is1.7 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 10 ppm +/-(20% of reading +0.5 ppm), calibration span isdaily 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 6hours.
Environmental Specifications	Similar to INOmax DS	Except ambient operation and storage pressureare 57 to 110 kPa (430 to 825 mmHg)
No Back-up Delivery	20 ppm @ 15 L/min.	0.25 L/min when delivered into 10 L/minprovides 20 ppm, plus INOblender may also beused.

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

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

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

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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.

Testing:

The testing indicated the INOmax DS met its design input specifications, design output specifications and risk analysis requirements. Testing completed included:

Validation of ventilators 1.

Standard(s):

The INOmax DS was designed to comply with the applicable portions of the following product standards

1. FDA Guidance Document for Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer (Special Controls).
1. IEC 60601-1, plus amendments: Medical Electrical Equipment
1. IEC 60601-1-2: EMC/EMI

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

Conclusions:

The INOmax DS device described in this Notice has the same intended use and indications, technological characteristics, and principles of operations 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. The difference does not present any new issues of safety or effectiveness. This device is substantially equivalent to the predicate devices.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle. The eagle is facing to the right. The logo is black and white.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. David M. Trueblood Director, Regulatory Affairs INO Therapeutics 6 State Route 173 Clinton, New Jersey 08809

AUG - 6 2008

Re: K080484

Trade/Device Name: INOmax DS (Delivery System), Model 10003 Regulation Number: 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: II Product Code: MRN, MRO, MRP, MRP, MRQ Dated: July 11, 2008 Received: July 11, 2008

Dear Mr. Trueblood:

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 - Mr. Trucblood

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that I'DA 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 (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.

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 Center for Devices and Radiological Health's (CDRH's) Office of Compliance at (240) 276-0120. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 vours.

TK O'Donnell's Lender's
for

Chiu S. Lin, Ph. D 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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Indications for Use

510(k) Number (if known):

Device Name: INOmax DS (Delivery System)

Indications for Use:

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 I /min of oxygen provides 20 ppm in the gas flow to a patients breathing circuit. It may also use the INOblender for backup.

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)

h the

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

Page 1 of 1

K080480 510(k) Number:

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.”