The Ulspira TS Nitric Oxide Therapy System is intended for use by healthcare professionals for the delivery of nitric oxide (NO) and the monitoring of inspired NO, NO2 and O2 concentrations for a patient undergoing inhaled Nitric Oxide (iNO) therapy.

The Ulspira TS must only be used in accordance with the indications, warnings and precautions described in the nitric oxide drug packaging inserts and labeling and is indicated for use in term and near-term (>34weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension. The primary targeted clinical setting is the Neonatal Intensive Care Unit (NICU) and secondary targeted clinical setting is the transport of neonates. Refer to this material prior to use.

The Ulspira TS primary NO therapy system delivers NO gas in the 0-80 ppm range while in the Constant Rate or flow sensing modes. This includes:

• Continuous integrated monitoring for inspired NO, NO2 and a comprehensive alarm system.

· A touch-screen user interface with a waveform display of the ventilation device flow as measured in the inspiratory limb.

· Cylinder handling facilitated by manual or an automatic cylinder switch which is reactive to the detected gas supply state of NO cylinders, and a low O2 pressure alarm when using an oxygen cylinder.

• An automated emergency dosing activated by certain high-risk alarms, which impact patient dosing, to avoid sudden cessation of therapy.

· Compatibility with a wide inspiratory flow rate range of 0.25-120 1/min, utilizing an automatically detected low or high flow sensor.

• An internal battery which provides at least two hours of uninterrupted therapy and a 12V DC inlet for additional external battery access.

The integrated Ulspira TS pneumatic backup NO therapy system provides backup NO delivery capability that is intended to deliver a continuous flow of NO mixed with O2, for iNO therapy which allows continuous treatment during transit within hospitals.

Device Description

Ulspira TS Nitric Oxide Therapy System delivers physician-prescribed NO therapy gas and monitors inspired Nitric Oxide, Nitrogen Dioxide, and Oxygen gas in combination with a respiratory device.

The main device functionalities of the Ulspira TS Nitric Oxide Therapy System include:

A primary delivery system to administer NO gas into a respiratory device circuit.
Monitoring of NO, NO2, and O2 gas concentrations close to the patient interface. ।
System includes a user interface that contains all controls used to set the NO delivery and monitoring parameters. All set i parameters as well as other information are shown on the user interface screen.
-The system will produce visual and audible alarms if vital parameters vary beyond preset or default limits.
-The system includes an integrated pneumatic back-up system for manual hand bagging in order to the rapy in the event of a failure of the primary delivery system and during manual ventilation.

The Ulspira TS system consists of the base unit, the mobile cart and bedside rail holder, and various components and accessories, including the gas regulators and patient kits for use with validated respiratory devices.

AI/ML Overview

Although the provided text describes the ULSPIRA TS Nitric Oxide Therapy System's indications for use, its technical characteristics compared to a predicate device, and the non-clinical performance data (verification and validation activities and applied standards), it does not contain explicit acceptance criteria or a study design and results that directly "prove the device meets the acceptance criteria" in terms of clinical performance metrics like sensitivity, specificity, or AUC.

The document focuses on demonstrating substantial equivalence to a predicate device (INOmax DSIR Plus) based on technical comparisons and non-clinical testing. This type of submission (510(k)) generally relies on demonstrating that the new device is as safe and effective as a legally marketed predicate, often without requiring extensive new clinical efficacy studies if technological differences are minor and can be addressed through non-clinical means.

Therefore, many of the requested details about clinical studies, expert consensus, and effects on human readers are not available in the provided text.

Here's a breakdown of what can be extracted and what is not present:

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

The document presents a comparison to a predicate device, showing "Comparison" remarks that indicate substantial equivalence or identify differences that are still considered acceptable (e.g., meeting regulatory guidance). It does not explicitly list "acceptance criteria" as pass/fail thresholds for clinical metrics but rather as similar technical specifications or compliance with standards.

Acceptance Criteria (Implied from predicate comparison/standards)	Reported Device Performance (ULSPIRA TS)
NO Administration Principle	NO delivery into the inspiratory limb of a ventilation device's patient circuit.
Range of NO gas concentration delivered	0-80 ppm
NO delivery accuracy	± 20% or 2 ppm, whichever is the greatest.
Operating Modes (fixed dose)	One mode for user-set NO dose based on measured respiratory device flow.
Backup power source	Pneumatic system
Backup NO delivery accuracy	Within ±20% of set value or ±2 ppm, whichever is the greatest.
Breathing circuit sample source location	On the inspiratory limb of the breathing circuit, after the humidifier.
Integrated NO Gas Analyzer	Yes
NO measurement accuracy	± (0.5 ppm +20 % of actual concentration) in 0-10 ppm; ± (0.5 ppm +10 % of actual concentration) in 10-100 ppm.
NO Measurement range	0 - 100 ppm
Integrated NO2 Gas Analyzer	Yes
NO2 measurement accuracy	±(20% or 0.5 ppm), whichever is the greatest.
NO2 measurement range	0 - 10 ppm
Integrated O2 Gas Analyzer	Yes
O2 measurement accuracy	± 3% volume fraction (v/v)
O2 measurement range	18 - 100 %
Battery backup time	6h
Compliance with relevant standards	(Implied by predicate and FDA guidance adherence)

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 primarily describes non-clinical performance data (verification and validation activities) rather than clinical study data. It mentions "performance testing (verification including primary & backup NO delivery, gas monitoring, & compatibility with ventilators identified in labeling)" but does not specify a sample size for a test set in cases or patients, nor does it indicate data provenance (country, retrospective/prospective). This suggests the testing was bench/lab-based rather than a clinical trial with patient data.

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

Not applicable/Not provided. The testing described is primarily engineering/performance verification against specifications and standards, not clinical ground truth established by experts.

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

Not applicable/Not provided. This refers to a clinical study method, which is not detailed in the provided non-clinical data.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable/Not provided. This device is a nitric oxide therapy system, not an AI-assisted diagnostic or treatment planning tool that would typically involve "human readers" or AI assistance in that context.

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

Not applicable/Not provided in this context. The device itself performs delivery and monitoring; there isn't an "algorithm only" performance that would be separate from the integrated system's function. The performance testing is for the whole system.

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

The "ground truth" for the non-clinical performance data would be the established engineering specifications, regulatory standards, and physical measurements (e.g., gas concentrations measured by reference instruments, flow rates, alarm thresholds, battery duration). There is no mention of clinical ground truth from expert consensus, pathology, or outcomes data, as this was not a clinical efficacy study.

8. The sample size for the training set

Not applicable/Not provided. This implies a machine learning or AI context, which is not described for this device's submission.

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

Not applicable/Not provided. As above, this is relevant for AI/ML models, not for the technical equivalence and performance verification described for this nitric oxide therapy system.

Summary

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Image /page/0/Picture/0 description: The image contains the logo for the U.S. Food and Drug Administration (FDA). The logo includes the Department of Health & Human Services symbol on the left. To the right of the symbol is the FDA acronym in a blue box, followed by the words "U.S. Food & Drug Administration" in blue text.

June 30, 2023

Airgas Therapeutics Steve Miller V.P. Regulatory and Compliance 12800 West Little York Road Houston, TX 77041

Re: K212409

Trade/Device Name: ULSPIRA TS Nitric Oxide Therapy System Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric oxide administration apparatus Regulatory Class: Class II Product Code: MRN, MRO, MRP, MRO, CCL Dated: January 30, 2023 Received: January 31, 2023

Dear Steve Miller:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

James J. Lee -S

James J. Lee, Ph.D. Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthesia Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K212409

Device Name Ulspira TS Nitric Oxide Therapy System

Indications for Use (Describe)

The Ulspira TS primary NO therapy system delivers NO gas in the 0-80 ppm range while in the Constant Rate or flow sensing modes. This includes:

• Continuous integrated monitoring for inspired NO, NO2 and a comprehensive alarm system.

· A touch-screen user interface with a waveform display of the ventilation device flow as measured in the inspiratory limb.

• An automated emergency dosing activated by certain high-risk alarms, which impact patient dosing, to avoid sudden cessation of therapy.

· Compatibility with a wide inspiratory flow rate range of 0.25-120 1/min, utilizing an automatically detected low or high flow sensor.

• An internal battery which provides at least two hours of uninterrupted therapy and a 12V DC inlet for additional external battery access.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) SUMMARY

The following summary is provided in accordance with 21 CFR 807.92:

A. DATE

May 31, 2023

B. SUBMITTER / SPONSOR

Airgas Therapeutics 12800 West Little York Road Houston, TX 77041

Contact Person: Steve Miller Airgas Therapeutics V.P. Regulatory and Compliance Phone (713) 896-2280

C. DEVICE

Trade Name of Device:	ULSPIRA TS Nitric Oxide Therapy System
Common or Usual Name:	Nitric Oxide Administration Apparatus (Primary)Nitric Oxide Administration Apparatus (Backup)Nitric Oxide AnalyzerNitrogen Dioxide AnalyzerOxygen Gas Analyzer
Classification:	Class II- 21 CFR 868.5165
Classification Name:	Nitric Oxide Administration Apparatus

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MRN (Primary), MRO, MRP, MRQ, CCL Product Codes:

D. PREDICATE DEVICE K200389, INOmax DSIR Plus
E. REFERENCE DEVICE(S) K171696, NOxBOXi Nitric Oxide Delivery System K193481, AeroNOx 2.0 Nitric Oxide Titration & Monitoring System

F. DEVICE DESCRIPTION

Ulspira TS Nitric Oxide Therapy System delivers physician-prescribed NO therapy gas and monitors inspired Nitric Oxide, Nitrogen Dioxide, and Oxygen gas in combination with a respiratory device.

The main device functionalities of the Ulspira TS Nitric Oxide Therapy System include:

A primary delivery system to administer NO gas into a respiratory device circuit.
Monitoring of NO, NO2, and O2 gas concentrations close to the patient interface. ।
System includes a user interface that contains all controls used to set the NO delivery and monitoring parameters. All set i parameters as well as other information are shown on the user interface screen.
-The system will produce visual and audible alarms if vital parameters vary beyond preset or default limits.
-The system includes an integrated pneumatic back-up system for manual hand bagging in order to the rapy in the event of a failure of the primary delivery system and during manual ventilation.

G. INDICATIONS FOR USE

The Ulspira TS Nitric Oxide Therapy System is intended for the delivery of nitric oxide (NO) and the monitoring of inspired NO, NO2 and O2 concentrations for a patient undergoing inhaled Nitric Oxide (iNO) therapy.

The Uspira TS must only be used in accordance with the indications, warnings and precautions described in the nitric oxide drug packaging inserts and labeling and is in term and near-term (>34weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardic evidence of pulmonary hypertension. The primary targeted clinical

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setting is the Neonatal Intensive Care Unit (NICU) and secondary targeted clinical setting is the transport of neonates. Refer to this material prior to use.

The Ulspira TS primary NO therapy system delivers NO gas in the Constant Rate or flow sensing modes. This includes:

Continuous integrated monitoring for inspired NO, NO2 and a comprehensive alarm system. .
A touch-screen user interface with a waveform display of the ventilation device flow as measured in the inspiratory limb. .
Cylinder handling facilitated by manual or an automatic cylinder switch which is reactive to the detected gas supply state of NO . cylinders, and a low O2 pressure alarm when using an oxygen cylinder.
An automated emergency dosing algorithm activated by certain high-risk alarms, which impact patid sudden . cessation of therapy.
Compatibility with a wide inspiratory flow rate range of 0.25-120 |/min, utilizing an automatically detected low or high flow . sensor.
An internal battery which provides at least two hours of uninterrupted therapy and a 12V DC inlet for additional external battery access.

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H. TECHNOLOGICAL CHARACTERISTICS - COMPARISON TO PREDICATE

Device name	INOmax DSIR Plus	Ulspira TS	Comparison
Comparison of general attributes, indication, patient population, operating environment, etc.
Product code(s)	-- MRN- MRP- MRQ	-- MRN, MRO- MRP- MRQ- CCL	Similar; the additional product codes (MRO – Apparatus Nitric Oxide Back-updelivery, CCL – Analyzer O2) are also part of the INOmax DSIR Plus system.
Regulation number	- 21 CFR 868.5165	- 21 CFR 868.5165	Identical
RegulationDescription	- Nitric oxide administration apparatus	- Nitric oxide administration apparatus	Identical
Device name	INOmax DSIR Plus	Ulspira TS	Comparison
Indications for Use	The INOmax DSIR Plus delivery system deliversINOMAX (nitric oxide for inhalation) therapy gas intothe inspiratory limb of the patient breathing circuit ina way that provides a constant concentration of nitricoxide (NO), as set by the user, to the patientthroughout the inspired breath. It uses a speciallydesigned injector module, which enables tracking ofthe ventilator waveforms and the delivery of asynchronized and proportional dose of NO. It may beused with most ventilators.	The Ulspira TS Nitric Oxide Therapy System is intended for useby healthcare professionals for the delivery of nitric oxide (NO)and the monitoring of inspired NO, NO2 and O2 concentrationsfor a patient undergoing inhaled Nitric Oxide (iNO) therapy.	SimilarBoth devices deliver controlled concentrations of NO into the inspiratory limbof a respiratory device circuit. Both devices contain gas monitors with alarmsfor NO, O2 and NO2.
		The Ulspira TS must only be used in accordance with theindications, contraindications, warnings and precautionsdescribed in the nitric oxide drug packaging inserts andlabeling and is indicated for use in term and near-term(>34weeks gestation) neonates with hypoxic respiratory failureassociated with clinical or echocardiographic evidence ofpulmonary hypertension. The primary targeted clinical settingis the Neonatal Intensive Care Unit (NICU) and secondarytargeted clinical setting is the transport of neonates. Refer tothis material prior to use.	Ulspira TS system facilitates cylinder switching.Ulspira TS system has an emergency dosing algorithm to avoid suddencessation of therapy, activated by certain high-risk alarms.
	The INOmax DSIR Plus provides continuous integratedmonitoring of inspired O2, NO2, and NO, and acomprehensive alarm system.The INOmax DSIR Plus incorporates a battery thatprovides up to 6 hours of uninterrupted NO delivery inthe absence of an external power source.The INOmax DSIR Plus includes a backup NO deliverycapability that provides a fixed flow of 250 mL/min ofNO which along with user supplied 10 L/min of oxygenprovides 20 ppm in the gas flow to a patientsbreathing circuit. It may also use the INOblender forbackup.	The Ulspira TS primary NO therapy system delivers NO gas inthe 0-80 ppm range while in the Constant Rate or flow sensingmodes. This includes:• Continuous integrated monitoring for inspired NO, NO2 andO2 and a comprehensive alarm system.• A touch-screen user interface with a waveform display of theventilation device flow as measured in the inspiratory limb.	Ulspira TS system has a broader inspiratory flow rate range utilizing two flowsensors, high and low.Indications for both devices follow the respective drug labeling for nitric oxide(currently neonates).
		• Cylinder handling facilitated by manual or an automaticcylinder switch which is reactive to the detected gas supplystate of NO cylinders, and a low O2 pressure alarm when usingan oxygen cylinder.
	The target patient population is controlled by the druglabeling for INOMAX and is currently neonates. Theprimary targeted clinical setting is the NeonatalIntensive Care Unit (NICU) and secondary targetedclinical setting is the transport of neonates.(Ref. K200389)	• An automated emergency dosing algorithm activated bycertain high-risk alarms, which impact patient dosing, to avoidsudden cessation of therapy.
		• Compatibility with a wide inspiratory flow rate range of 0.25-120 l/min, utilizing an automatically detected low or high flowsensor.
		• An internal battery which provides at least two hours ofuninterrupted therapy and a 12V DC inlet for additionalexternal battery access.
		The integrated Ulspira TS pneumatic backup NO therapysystem provides backup NO delivery capability that is intendedto deliver a continuous flow of NO mixed with O₂, for iNOtherapy which allows continuous treatment during transitwithin hospitals.
Device name	INOmax DSIR Plus	Ulspira TS	Comparison
Physicaldimensions andweight (excl.carrier/cart)	Weight: 5.3 kgWidth: 350 mmDepth: 160 mmHeight: 220 mm	Weight: 7.0 kgWidth: 320 mmDepth: 150 mmHeight: 300 mm	Different but substantially equivalent
NO gas connectors	CGA 626	CGA 626	Identical
NO Injectionlocation	NO injection connected between ventilator andhumidifier.	NO injection connected between ventilator and humidifier.	Identical
Battery backup	Yes	Yes	Identical
Battery backuptime	6h	2h	Different, however both devices meet the US Food and Drug Administrationspecial controls guidance.
Power Supply -Main	Voltage: 100-240V, 50 - 60Hz	Voltage: 100-240V, 50 - 60Hz	Identical
Automated Pre-Usecheck	Yes	Yes	Identical
Alarms
NO Delivery/FlowSensor Alarms	Yes	Yes	Substantially equivalentBoth devices include alarms for failures in injection/delivery and for stop indelivery/no treatment of patient. The Ulspira TS system also includes specificalarms in relation to the respiratory device/ventilator flow.
PowerSupply/BatteryAlarms	Yes	Yes	Substantially equivalentBoth devices include alarm(s) for low battery power, additionally the Ulspira TSsystem also includes technical alarms in relation to failures in different parts ofthe power supply system.
NO, NO2, O2Monitoring Alarms	Yes	Yes	Substantially equivalent
Device name	INOmax DSIR Plus	Ulspira TS	Comparison
Primary NO administration system
NO administrationprinciple	NO delivery into the inspiratory limb of a ventilationdevice's patient circuit.	NO delivery into the inspiratory limb of a ventilation device'spatient circuit.	Identical
Range of NO gasconcentrationdelivered	0-80 ppm	0-80 ppm	Identical
NO deliveryaccuracy	$±$ 20% or 2 ppm, whichever is the greatest.	$±$ 20% or 2 ppm, whichever is the greatest.	Identical
Operating Modes	The predicate device incorporates one mode thatprovides a user set dose of NO into the inspiratorylimb of the respiratory device circuit, based on themeasured respiratory device flow.(Note. The integrated pneumatic backup provides afixed flow (0.25 l/min) of NO.)	The subject device incorporates two modes (Autosense and JetSense) that provides a user set dose of NO into the inspiratorylimb of the respiratory device circuit, based on the measuredrespiratory device flow.The subject device also includes a third mode, Constant Rate,which provides flow of NO (0.5 - 60 l/min) into the inspiratorylimb of the respiratory device circuit.	Different, but substantially equivalent. Both devices support fixed dosemode(s) that delivers a user set dose of NO into the inspiratory limb of therespiratory device circuit based on the measured respiratory device flow.The Jet Sense mode of the Ulspira TS system is specifically optimized in relationto a specific respiratory deviceThe Ulspira TS system supports a Constant Rate mode as part of the primarydelivery system that provides NO into the inspiratory limb of the respiratorydevice circuit, based on a user set respiratory device flow and user set NOdose. A similar function for the INOmax DSIR Plus is the integrated pneumaticbackup system when used with the on screen feedback for estimated NO dose.This integrated pneumatic backup system provides a fixed flow of NO into theinspiratory limb of the respiratory device circuit and the on screen feedbackindicates estimated dose and monitored values.

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Backup NO administration system

Backup power source	Pneumatic system	Pneumatic system	Identical
Backup NO Administration	Backup system delivering a constant flow of NO to the inspiratory limb of a ventilation device patient circuit.	Backup system delivering a user set concentration of NO, via adjustment of O2 flow, to the patient via a resuscitator.	Different, but the special control applicable for these devices describes both types of systems.
Backup NO delivery accuracy	Within ±20% of set value or ±2 ppm, whichever is the greatest.	Within ±20% of set value or ±2 ppm, whichever is the greatest.	Identical

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Device name	INOmax DSIR Plus	Ulspira TS	Comparison
Gas analysis (NO, NO2, O2) - General characteristics
Breathing circuitsample sourcelocation	On the inspiratory limb of the breathing circuit, afterthe humidifier.	On the inspiratory limb of the breathing circuit, after thehumidifier.	Identical
Sample flow rate	230 ml/min	150 ml/min	Minor difference. The Ulspira TS system meets its measuring accuracyrequirements with a lower sample flow rate from the patient's breathingcircuit.
NO gas analysis
Integrated NO GasAnalyzer	Yes	Yes	Identical
NO measurementaccuracy	+- (0.5 ppm +20 % of actual concentration) in therange 0-10 ppm	+- (0.5 ppm +20 % of actual concentration) in the range 0-20ppm	Different, but substantially equivalent
	+- (0.5 ppm +10 % of actual concentration) in therange 10-100 ppm	+- (0.5 ppm +10 % of actual concentration) in the range 20-120ppm
NO Measurementrange	0 - 100 ppm	0 - 120 ppm	Different. The Ulspira TS system is verified for and facilitates NO measurementin a wider range.
NO2 gas analysis
Integrated NO2 GasAnalyzer	Yes	Yes	Identical
NO2 measurementaccuracy	±(20% or 0.5 ppm), whichever is the greatest.	±(20% or 0.5 ppm), whichever is the greatest.	Identical
NO2 measurementrange	0 - 10 ppm	0 - 30 ppm	Different. The Ulspira TS system is verified for and facilitates NO2 measurementin a wider range.
Device name	INOmax DSIR Plus	Ulspira TS	Comparison
O2 gas analysis
Integrated O2 GasAnalyzer	Yes	Yes	Identical
O2 measurementaccuracy	$\pm$ 3% volume fraction (v/v)	$\pm$ (2.5 % volume fraction + 2.5 % of gas concentration)	Different, but substantially equivalent. The Ulspira TS meets requirements asspecified in the special control applicable for this device.
O2 measurementrange	18 - 100 %	18 - 100 %	Identical

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l. NON-CLINICAL PERFORMANCE DATA

The following verification and validation activities have been performed to demonstrate that the design output of the modified devices meet the design input requirements:

System (System test, regression tests, free user testing, comparative/waveform testing)
Software (Code review, static code analysis, unit tests, integration tests)
. Performance testing (verification including primary & backup NO delivery, gas monitoring, & compatibility with ventilators identified in labeling)
. Safety testing (verification)
. Biocompatibility testing (Volatile organic compounds, particulate matter, leachable substances for prolonged contact duration)
. Reprocessing testing (Multiple reprocessing, method effectiveness validation)
. Human factors validation
Respiratory device validation

The device has been verified and validated in compliance with the following product standards and US FDA Guidance documents:

FDA guidance - Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer (January 24, 2000)
FDA guidance - Use of International Standard ISO 10993-1, "Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process"
(September 4, 2020)
. FDA guidance - Applying Human Factors and Usability Engineering to Medical Devices.(February 3, 2016)
. ANSI/AAMI ES 60601-1:2005 + A1 2012, Medical electrical equipment – Part 1: General requirements for basic safety and essential performance, Recognition Number: 19-4
. IEC 60601-1-2:2014, Medical electrical equipment – Part 1-2: General requirements for basic safety and essential performance – Collateral standard: Electromagnetic disturbances – Requirements and Test Recognition Number: 19-8
. IEC 60601-1-8:2006 + A1:2012, Medical electrical equipment – Part 1-8: General requirements for basic safety and essential performance – Collateral standard: General requirements, test and guidance for alarm systems in medical electrical equipment and medical electrical systems Recognition Number: 5-76

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. 4ISO 80601-2-12:2011, Medical electrical equipment -- Part 2-12: Particular requirements for basic safety and essential performance of critical care ventilators Recognition Number: 1-98
. 21SO 80601-2-55:2018, Medical electrical equipment - Part 2-55: Particular requirements for the basic safety and essential performance of respiratory gas monitors Recognition Number: 1-140
. IEC 62133-1:2017, Secondary Cells And Batteries Containing Alkaline Or Other Non-Acid Electrolytes – Safety Requirements For Portable Sealed Secondary Cells, And For Batteries Made From Them, For Use In Portable Applications – Part 1: Nickel Systems
. [Rec. Number2-258] ISO 10993-1:2018 Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process
. [Rec. Number2-245] ISO 10993-5:2009 Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity
[Rec. Number2-296] ISO 10993-10:2021 Biological evaluation of medical devices - Part 10: Tests for sensitization
. [Rec. Number2-255] ISO 10993-11:2017 Biological evaluation of medical devices - Part 11: Tests for systemic toxicity
. [Rec. Number2-237] ISO 10993-17:2002 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances
. [Rec. Number2-291] ISO 10993-23:2021 Biological evaluation of medical devices - Part 23: Tests for irritation
. [Rec. Number1-134] ISO 18562-1:2017 Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 1: Evaluation and testing within a risk management process
. [Rec. Number1-135] ISO 18562-2:2017 Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 2: Tests for emissions of particulate matter
[Rec. Number1-136] ISO 18562-3:2017 Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 3: Tests for emissions of volatile organic compounds
. [Rec. Number1-137] ISO 18562-4:2017 Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 4: Tests for leachables in condensate
[Rec. Number2-295] USP-NF M98900_01_01 <151> Pyrogen Test (USP Rabbit Test)

In addition, the following standards have been applied for gas-connectors: The connector to High-Pressure O2 gas is in accordance with CGA V-5:2008 Recognition Number: 1-81

1 Parts applicable for respiratory device validation

2 Applicable for O₂ monitoring

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The NO gas regulator cylinder connection is in accordance with CGA V-1:2013 Recognition Number: 1-100

J. CONCLUSIONS

The above described non-clinical data support the substantial equivalence of the device with the predicate device. The supporting hardware, and the software verification and validation and usability testing demonstrate that the Ulspira TS Nitric Oxide Therapy System performs as intended in the specified use conditions. Risk assessments and completed testing did not raise different questions of safety and effectiveness. Airgas Therapeutics concludes that the performance data for the subject device shows that it is substantially equivalent to the cleared predicate device.

Regulation Number and Section

§ 868.5165 Nitric oxide administration apparatus.

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