INOMAX DS (DELIVERY SYSTEM) by INO THERAPEUTICS LLC

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 (Delivery System) provides a constant dose of INOmax (nitric oxide) therapy gas into the inspiratory limb of the ventilator circuit. The INOmax DS (Delivery System) 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 requlator is attached via tubing to the INOmax DS (Delivery System) 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 (Delivery System), 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 (Delivery Svstem) to deliver a constant dose of INOmax regardless of the ventilator flow pattern or breath rate.

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

The INOmax DS (Delivery System) 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 shutdown, the INOmax DS (Delivery System) 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

This document describes the INOmax DS (Delivery System), a nitric oxide administration apparatus. However, it does not contain information about acceptance criteria or a study that specifically proves the device meets acceptance criteria in the context of diagnostic accuracy, which is typically what those terms imply for AI/ML devices.

Instead, this submission is a 510(k) for a medical device (not an AI/ML algorithm) that relies on demonstrating substantial equivalence to a predicate device. The "acceptance criteria" here are more akin to engineering specifications and performance characteristics compared against the predicate device, rather than diagnostic performance metrics. The "study" refers to engineering testing and validation to ensure the device meets its design specifications and complies with relevant standards.

Therefore, I cannot populate the requested table and sections as they would apply to an AI/ML diagnostic device. I will extract the relevant information regarding performance specifications and testing as presented for this hardware device.

Here's the breakdown of what is available in the provided text:

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

The document provides a comparison table between the INOvent Delivery System (predicate) and the INOmax DS (Delivery System). These are more akin to performance specifications than acceptance criteria in a diagnostic sense.

Specification	INOmax DS (Delivery System) Performance (Reported)
Indications for Use	Except battery backup is 6 hours; 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 220mm, Width 350mm, Depth 160mm, Weight 5.5Kg
Ventilator Compatibility	2-60 L/min for inspiratory flow for neonatal and 4-120 L/min for adult.
NO Delivery	NO set resolution is 0.1/1/5 ppm depending on range; accuracy is +/- 20% indicated or 2 ppm whichever greater; NO inlet pressure is 1.7 to 2.3 Bar (25 to 33 psig).
NO Cylinder INOmax	Same as predicate.
Gas Monitoring	NO range resolution is 0 to 10 ppm +/- (20% of reading +0.5 ppm); calibration span is daily zero with span at pre-use test if needed; NO accuracy is +/- 20% of reading +0.5 ppm.
Injector Module	Same as predicate.
NO Delivery Shut Off	Same as predicate.
Calibration Gas Cylinders	INOcal calibration gas, INO Therapeutics LLC; NO Cal gas 45 ppm +/- 4%; NO2 Cal gas 10 ppm +/- 10%.
Electrical Specifications	Except no nurse call and battery back-up is 6 hours.
Environmental Specifications	Ambient operation and storage pressure are 57 to 110 kPa (430 to 825 mmHg).
NO Back-up Delivery	0.25 L/min when delivered into 10 L/min provides 20 ppm; INOblender may also be used.

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

This information is not provided in the document. The document describes engineering and software validation, not a clinical study with a "test set" in the context of diagnostic performance.

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 provided and is not relevant for this type of device submission, which focuses on hardware and software function, not diagnostic interpretation.

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

This information is not provided and is not relevant for this type of device submission.

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

An MRMC study was not done. This device is a hardware delivery system, not an AI/ML diagnostic tool that assists human readers.

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

This is not applicable as the device is a hardware delivery system, not an algorithm.

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

The "ground truth" for this device's performance validation is its design input specifications and risk analysis requirements. The testing confirmed that the device performed according to these engineering specifications and safety requirements, and in compliance with applicable standards.

8. The sample size for the training set

This information is not provided and not applicable. This is not an AI/ML device that requires a "training set."

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

This is not applicable as the device is a hardware delivery system, not an AI/ML algorithm.

Summary

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K081691
Page 1 of 6

AUG 2 8 2008

Image /page/0/Picture/2 description: The image shows the logo for INC Therapeutics. The logo is in black and white and features the letters "INC" in a bold, sans-serif font. The "C" in "INC" is larger than the other letters and curves around the word "Therapeutics", which is written in a smaller, sans-serif font to the right of "INC". A line is underneath the word "Therapeutics".

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

June 12, 2008 Date Prepared:
510(k) Summary of Safety and Effectiveness Information for Subject: the INOmax DS. This summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 1992 and 21CFR 807.92.

Proprietary Name: INOmax DS

Common Name(s): Nitric Oxide Administration Apparatus (primary) Nitric Oxide Administration Apparatus, Back-up System Nitric Oxide Analyzer Nitrogen Dioxide Analyzer
Class II 21CFR868.5165, MRN (primary) Classification(s): Class II - 21CFR868.5165, MRO Class II - 21CFR868.2380, MRP Class II - 21CFR868.2385, MRQ

Anesthesiology Panel:

1NO Therapeutics' INOmax™ DS (Delivery System) Predicate Device(s): 510(k) Number K061901 (primary) INO Therapeutics' INOmax DS (Delivery System) 510(k) Number K070867 INO Therapeutics' INOmax DS (Delivery System) 510(k) Number K071516 Datex-Ohmeda INOvent Delivery System (now GE Healthcare) 510(k) Number K974562

David M. Trueblood, Director, Regulatory Affairs Contact Person:
Patient Population: The targeted patient population is neonates. This is derived from the INOmax® drug package labeling.

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The primary targeted clinical setting is the Neonatal Intensive Clinical Setting: Care Unit (NICU) and secondary targeted clinical setting is the transport of neonates as derived from the INOmax drug package labeling.
The technology utilized in the INOmax DS (Delivery System) Technology: is very similar to the Datex-Ohmeda INOvent Delivery System (now GE Healthcare), with many of the subsystems and components being unchanged.

Specification	INOvent Delivery System	INOmax DS (Delivery System)
Indications for Use	Similar to INOmax DS	Except battery backup is 6 hoursand provides an integrated backupsystem for delivering a fixed flow ofNO into a constant flow of breathingcircuit 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 inspiratoryflow for neonatal and 4-120 L/minfor adult.
NO Delivery	Similar to INOmax DS	Except NO set resolution is 0.1/1/5ppm depend on range, accuracy is+/- 20% indicated or 2 ppmwhichever greater, and NO inletpressure is 1.7 to 2.3 Bar (25 to 33psig).
NO Cylinder INOmax	Same as INOmax DS	Same
Gas Monitoring	Similar to INOmax DS	Except NO range resolution is 0 to10 ppm +/- (20% of reading +0.5ppm), calibration span is daily zerowith span at pre-use test if needed,and NO accuracy is +/- 20% ofreading +0.5 ppm.
Injector Module	Same as INOmax DS	Same
NO Delivery Shut Off	Same as INOmax DS	Same

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K08116091
Page 308 6

Specification	INOvent Delivery System	INOmax DS (Delivery System)
Calibration Gas Cylinders	NO Cal gas 40-80 ppm+/- 4%NO2 Cal gas 10-15 ppm +/- 10%	INOcal calibration gas, INOTherapeutics LLCNO Cal gas 45 ppm +/- 4%NO2 Cal gas 10 ppm +/- 10%
Electrical Specifications	Similar to INOmax DS	Except no nurse call and batteryback-up is 6 hours.
EnvironmentalSpecifications	Similar to INOmax DS	Except ambient operation andstorage pressure are 57 to 110 kPa(430 to 825 mmHg) and
No Back-up Delivery	20 ppm @ 15 L/min.	0.25 L/min when delivered into 10L/min provides 20 ppm, plusINOblender may also be used.

The materials selected were based upon INO Therapeutics' Material(s) 1NOmax DS (Delivery System) and Datex-Ohmeda INOvent Delivery System (now GE Healthcare).

Device Description: The INOmax DS (Delivery System) provides a constant dose of INOmax (nitric oxide) therapy gas into the inspiratory limb of the ventilator circuit. The INOmax DS (Delivery System) 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 requlator is attached via tubing to the INOmax DS (Delivery System) using one of the two NO/NO2 quick connect inlets on the back of the machine.

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Image /page/3/Picture/0 description: The image shows handwritten text that appears to be a combination of alphanumeric characters. The top line reads 'KOS816691', while the bottom line reads 'Page 4 of 6'. The text is written in a casual, handwritten style, and the overall image has a simple, unadorned appearance.

The INOmax enters the back of the INOmax DS (Delivery System), 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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K081691
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Indications for Use: 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 testing indicated the INOmax DS (Delivery System) met Testing: its design input specifications, design output specifications and risk analysis requirements. Testing completed included:

Validation of neonatal ventilator mode 1.
Validation of software version 1.3.0 and intermediate 2. versions, leading to the release of software version 1.3.4 with no anomalies.

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K081691
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The INOmax DS (Delivery System) was designed to comply Standard(s): with the applicable portions of the following product standards

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

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 INOmax DS (Delivery System) device described in this Conclusions: 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 (Delivery System): K061901). The only differences are that a newly validated neonatal ventilator mode has been qualified with the INOmax DS (Delivery System) and minor software changes were made in order to accommodate very low, non-adjustable bias flow rates, to respond to user feedback and to improve gas cell ambient pressure (altitude) compensation and the detection of incorrect calibration gas. These differences do not present any new issues of safety or effectiveness. This device is substantially equivalent to the predicate devices.

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Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

AUG 2 8 2008

Mr. David M. Trueblood Director, Regulatory Affairs INO Therapeutics 2820 Walton Commons West Madison, Wisconsin 53718

Re: K081691

Trade/Device Name: INOmax DS (Delivery System) Regulation Number: 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: II Product Code: MRN, MRO, MRP, MRP, MRQ Dated: July 31, 2008 Received: August 1, 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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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 (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.

CWR

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): K0811691

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.

× Prescription Use (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)

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

Page 1 of 1

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.”