The NOxBOXi Nitric Oxide Delivery System is intended for use by healthcare professionals for the delivery and monitoring of a constant (user set) concentration of nitric oxide (NO) and the monitoring of NO2 and O2 in the inspiratory ventilator lines of a patient undergoing nitric oxide therapy (iNO).

The NOxBOXi Nitric Oxide Delivery System Includes:

· The NOxBOXi head unit, which delivers NO gas while in the intelligent delivery mode.
· Continuous monitoring and alarms for NO, O2, and NO2.
The integrated NOxMixer, which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O2, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals.

The NOxBOXi Nitric Oxide Delivery System must only be used in accordance with the indications, warnings and precautions described in the nitric oxide drug packaging (currently neonates). Refer to this material prior to use.

Device Description

The NOxBOXi Nitric Oxide Delivery System (NOxBOXi) simultaneously delivers Nitric Oxide (NO) medical gas, while monitoring Nitric Oxide, Nitrogen Dioxide and Oxygen levels in the inspiratory limb of a ventilator for patients undergoing inhaled Nitric Oxide Therapy.

The system is designed for use by healthcare professionals to administer treatment to patients undergoing inhaled Nitric Oxide (iNO) therapy. The NOxBOXi will deliver nitric oxide in a synchronous manner to a single patient.

An integrated component to the NOxBOXi, the NOxMixer is intended to deliver a continuous flow of Nitric Oxide from the NOxBOXi, mixed in line with Oxygen (O₂) for use in iNO therapy. The NOxMixer will be used in conjunction with manually bagging a patient.

The NOxBOXi includes the NOxBOXi Head Unit, a NOxFLOW sample line, two NO feed hoses, two regulators (connector type dependent on the gas supplier), a test circuit, NO, O₂ & NO2 monitors, power supply, drainage syringe, Operating Manual & Technical Guide.

Optional accessories include 4 separate NOxKITs (22mm, 12 mm, & 10mm), one way valve for HFOV (High Frequency Oscillatory Ventilation), bagging kits (hyperinflation & selfinflating) and circuit reducers (22f – 15m).

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the NOxBOXi Nitric Oxide Delivery System, based on the provided text:

Important Note: The provided document is a 510(k) summary for a medical device. This type of submission relies on demonstrating "substantial equivalence" to a predicate device, rather than proving efficacy and safety through extensive clinical trials as seen with PMAs. Therefore, most of the studies mentioned are non-clinical (bench testing, software validation, usability testing), and a multi-reader multi-case (MRMC) comparative effectiveness study or standalone algorithm-only performance is not applicable in this context. The acceptance criteria are largely based on engineering and safety standards rather than clinical performance metrics like sensitivity and specificity.

1. Table of Acceptance Criteria and Reported Device Performance

Given that this is a 510(k) summary for a device delivering and monitoring a gas, the "acceptance criteria" and "device performance" are primarily related to the accuracy of gas delivery, monitoring, and safety standards.

Acceptance Criteria / Performance Aspect	Reported Device Performance	Comments
NOxBOXi (General)
Indication for Use	Delivers and monitors constant user-set NO concentration, monitors NO2 and O2 in inspiratory ventilator lines.	Directly meets the stated indications for use.
Compliance with Regulatory Standards	Passed electrical safety, EMC, biocompatibility, and software validation.	Complies with ISO 60601-1, ISO 60601-1-2, ISO 80601-2-55, ISO 10993-1, ISO 62304, ISO 62366.
Battery Backup Capability	4 hours without AC power.	Different from predicate (6 hours), but deemed acceptable for emergency backup situations due to hospital generator availability.
Pre-use Setup Time	Instant set-up.	Reduced from predicate (4-6 mins), indicating improved usability.
NO/NO2/O2 Monitoring & Delivery
NO concentration provided	0.0 to 80 ppm	Identical to predicate.
NO monitor	Yes	Identical to predicate.
O2 monitor	Yes	Identical to predicate.
NO & NO2 Monitoring Accuracy	+/- 2% or 0.2 ppm (whichever is greater)	Improved compared to predicate (+/-20% or 2ppm). The NOxBOXi uses a closed-loop system for automatic adjustment.
NO2 monitor & alarm	Yes	Identical to predicate.
NO flow rate (sample flow rate)	225 ml/min	Minor difference from predicate (250 ml/min), but still meets measuring accuracy requirements.
Purity of NO drug delivery	Tested	Acceptable.
Acceptable/minimal production of NO2	Tested	Acceptable.
NO analyzer accuracy	Tested	Acceptable (as above: +/- 2% or 0.2 ppm).
NO2 analyzer accuracy	Tested	Acceptable (as above: +/- 2% or 0.2 ppm).
Compatibility testing of ventilators	Tested	Compatible with listed ventilators.
NOxMixer (Backup / Manual Mode)
Manual bagging & backup system	NOxMIXER®	Integrated with NOxBOXi system, provides a continuous treatment option during transit and transfer.
NO dosing range in manual mode	0 - 185 ppm (800 ppm cylinders)	Expanded user-selectable dose range compared to predicate (5-80ppm or 2.5-40ppm).
NO dosing accuracy in manual mode	+/- 20% or 2 ppm (for 5-80 ppm, 800 ppm cylinder, and 5-14 L/min O2 flow); +/- 40% or 4 ppm (for 0 to <5 ppm or >80 to 185 ppm, or 2 to <5 L/min or >14 to 25 L/min O2 flow)	Similar accuracy for the limited range of the predicate, but with an expanded user-selectable dose range.
NO flow in manual mode	Adjustable 50 – 600 mL/min of NO/N2	User adjustable flow range; predicate was fixed 250 mL/min.
O2 flow range in manual bagging mode	2 to 25 L/min of O2	Expanded user-selectable flow range compared to predicate (5 to 14 L/min).
Oxygen inlet pressure	3.5 – 4.5 bar	Different from predicate (3-5 bar), but deemed substantially equivalent as this pressure is typically available in clinical settings.
NO delivery pressure	1.65 bar from manual control valve	Different from predicate (1.7 to 2.4 bar), but deemed substantially equivalent for neonates.
Monitoring during manual bagging	Yes	Equivalent to predicate.
Alarms active during bagging	Yes	Equivalent to predicate.
Backup accuracy	+/- 20% or 2 ppm (for 5-80 ppm, 800 ppm cylinder); +/- 40% or 4 ppm (for 0 to <5 ppm or >80 to 185 ppm, 800 ppm cylinder)	Equivalent to predicate.
Volatile organic compounds (VOC)	Three orders of magnitude below OSHA permissible exposure levels.	Acceptable.
Particulate matter	Well below EPA's maximum limits for total suspended particulates.	Acceptable.

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

Test Set Sample Size: Not explicitly stated in terms of patient numbers or specific data points. The testing described focuses on device performance, electrical safety, EMC, software validation, biocompatibility, and usability, which are typically performed on the device itself and its components, or with simulated data/environments.
Data Provenance: The studies are primarily non-clinical bench testing and simulations. No patient data (retrospective or prospective) is mentioned as being used for the substantial equivalence determination for the device's technical performance.

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

Number of Experts: Not applicable. The "ground truth" for non-clinical performance and safety tests is established by published engineering standards (e.g., ISO, IEC), regulatory guidelines, and internal specifications, rather than expert interpretation of clinical data.
Qualifications of Experts: N/A for establishing ground truth in this context. Test engineers and qualified personnel would have performed and validated the tests according to established protocols.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. Adjudication methods (like 2+1 or 3+1 consensus) are typically used in clinical studies where multiple human readers interpret medical images or data and their interpretations need to be reconciled to form a robust "ground truth." For non-clinical device testing, results are usually compared directly against pre-defined performance specifications from recognized standards or internal design requirements.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

MRMC Study: No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging devices where human readers interpret medical images, and the goal is to assess how a new technology (e.g., AI) impacts their diagnostic performance. The NOxBOXi is a gas delivery and monitoring system, not an imaging diagnostic tool.

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

Standalone Performance Study: Yes, in essence, the "non-clinical performance data" and "software verification and validation" sections describe standalone testing of the device's functional integrity. The device's ability to precisely deliver and monitor gases according to its specifications, and the functionality of its software, were tested independently of human intervention during the gas delivery process after initial user setup. However, it's important to differentiate this from "standalone AI performance" often discussed for diagnostic AI, as this device primarily involves control systems and sensor-based monitoring rather than complex AI interpretation.

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

Type of Ground Truth: The ground truth for the non-clinical tests involved:
- Engineering Standards and Specifications: For electrical safety (ISO 60601-1), EMC (ISO 60601-1-2), respiratory gas monitors (ISO 80601-2-55), biocompatibility (ISO 10993-1), and software (FDA Guidance, ISO 62304).
- Reference Measurements/Calibrated Equipment: For accuracy of NO delivery, NO/NO2 analyzer accuracy, purity of gas, and NO2 production.
- Usability Feedback: For usability testing (ISO 62366, FDA guidance), user feedback identifies issues and informs design improvements, rather than establishing a "truth" about a medical condition.
- Predicate Device Performance: Used as a benchmark for comparison to demonstrate substantial equivalence, rather than strict "ground truth."

8. The Sample Size for the Training Set

Training Set Sample Size: Not applicable. This device is a hardware system with embedded software, not a machine learning or AI model that requires a "training set" in the conventional sense of data-driven learning. Its operating parameters are based on physical laws, engineering principles, and pre-programmed algorithms, not learned from a dataset.

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

Ground Truth for Training Set: Not applicable, as there is no "training set" for an AI model. The "ground truth" for the device's design and operational parameters is established through scientific principles, engineering design, and adherence to relevant national and international standards for medical gas delivery and monitoring systems.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Praxair Distribution, Inc Michael Skrjanc Executive Director, Quality, Regulatory Compliance and Product Safety 10 Riverview Drive Danbury, Connecticut 06810

Re: K171696

Trade/Device Name: NOxBOXi Nitric Oxide Delivery System Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: Class II Product Code: MRN, MRP, MRQ, CCL, MRO Dated: October 1, 2018 Received: October 1, 2018

Dear Michael Skrjanc:

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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice

(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Todd D. Courtney -

Tina Kiang, Ph.D. for Acting Director Division of Anesthesiology, General Hospital, Respiratory, 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) K171696

Device Name NOxBOXi Nitric Oxide Delivery System

Indications for Use (Describe)

The NOxBOXi Nitric Oxide Delivery System Includes:

· The NOxBOXi head unit, which delivers NO gas while in the intelligent delivery mode.
· Continuous monitoring and alarms for NO, O2, and NO2.
The integrated NOxMixer, which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O2, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals.

Type of Use (Select one or both, as applicable)
> Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary NOxBOXi Nitric Oxide Delivery System K171696

1. Submission Sponsor

Praxair Distribution, Inc. (PDI) 10 Riverview Dr. Danbury, CT 06810 Phone: 330.949.3324 Contact: Mike Skrjanc, Executive Director, Quality, Regulatory Compliance and Product Safety

2. Submission Correspondent

Michael E. Skrjanc Executive Director, Quality, Regulatory Compliance and Product Safety Praxair Distribution, Inc. 10 Riverview Drive Danbury, CT 06810

3. Date Revised

September 23, 2018

4. Device Identification

Trade/Proprietary Name:	NOxBOXi Nitric Oxide Delivery System
Classification Names:	Nitric Oxide administration apparatus, back-up and gasanalyzers
Common/Usual Name:	Nitric Oxide administration apparatus – primaryNitric Oxide administration apparatus – backupNitric Oxide AnalyzerNitrogen Dioxide AnalyzerOxygen Gas Analyzer
Classification Regulationand Product Code:	21 CFR 868.5165 - primary	MRN
Additional Product Codes:	21 CFR 868.5165 – backup21 CFR 868.2380 – Nitric Oxide Analyzer21 CFR 868.2385 - Nitrogen Dioxide Analyzer21 CFR 868.1720 – Oxygen Gas Analyzer	MRCMRPMRCCCL
Device Class:Classification Panel:	Class IIAnesthesiology

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5. Legally Marketed Predicate Device(s)

There are two predicate devices chosen for this submission.

1. K092545 INO Therapeutics' INOmax DS Delivery System
1. K122689 INO Therapeutics' INOblender Nitric Oxide Administration Back-up system.

Note that both the functionality of the INOmax DS Delivery System and INOblender NO administration backup unit are integrated into the NOxBOXi Nitric Oxide Delivery System.

6. Device Description

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7. Indication for Use Statement

NOxBOXi Nitric Oxide Delivery System is intended for use by healthcare professionals for the delivery and monitoring of a constant (user set) concentration of nitric oxide (NO) and the monitoring of NO2 and O2 in the inspiratory ventilator lines of a patient undergoing nitric oxide therapy (iNO).

The NOxBOXi Nitric Oxide Delivery System includes:

The NOxBOXi head unit, which delivers NO gas while in the intelligent delivery mode. ●
Continuous monitoring and alarms for NO, O2 and NO2.
. The integrated NOxMixer which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O2, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals.

The NOxBOXi Nitric Oxide Delivery System must only be used in accordance with the indications, contraindications, warnings and precautions described in the nitric oxide drug packaging inserts and labeling (currently neonates). Refer to this material prior to use.

8. Substantial Equivalence Discussion

The following table compares the NOxBOXi to the predicate device with respect to intended use, technological characteristics and principles of operation.

Comparison of Characteristics
Manufacturer	Praxair Distribution, Inc.	INO Therapeutics	Comparison
Trade Name	NOxBOXi Nitric Oxide DeliverySystem	INOmax DS
510(k) Number	K171696	K092545 K122689	N/A
Product Code	MRN, MRO, MRP, MRQ	MRN, MRO, MRP, MRQ	Identical
RegulationNumber	21CFR 868.5165, .2380, .2385	21 CFR 868.5165, .2380, .2385	Identical
Regulation Name	Nitric Oxide administrationapparatus, back-up and gasanalyzers	Nitric Oxide administrationapparatus, back-up and gasanalyzers	Identical
Indications forUse	NOxBOXi Nitric OxideDelivery System is intendedfor use by healthcareprofessionals for thedelivery and monitoring ofa constant (user set)concentration of nitricoxide (NO) and themonitoring of NO2 and O2in the inspiratory ventilator	The INO Therapeutics INOmaxDS delivers INOmax (nitricoxide of inhalation) therapygas into the inspiratory limbof the patient breathingcircuit in a way that provides aconstant concentration ofnitric oxide (NO), as set by theuser, to the patientthroughout the inspiredbreath. It uses a specially	Similar, both devicesprovide controlledconcentrations of NOinto the inspiratoryventilation circuit,contain monitors andalarms for NO, O2 andNO2.The NOxBOXi batteryfunctionality is
Manufacturer	Praxair Distribution, Inc.	INO Therapeutics	Comparison
Trade Name	NOxBOXi Nitric Oxide Delivery System	INOmax DS
	lines of a patient undergoing nitric oxide therapy (iNO).The NOxBOXi Nitric Oxide Delivery System includes:The NOxBOXi head unit, which delivers NO gas while in the intelligent delivery mode. Continuous monitoring and alarms for NO, O₂ and NO₂. The integrated NOxMixer which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O₂, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals. The NOxBOXi Nitric Oxide Delivery System must only be used in accordance with the indications, contraindications, warnings and precautions described in the nitric oxide drug packaging inserts and labeling (currently neonates). Refer to this material prior to use.	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 250ml/min of NO, which along with user supplied 10L/min of oxygen, provides 20ppm in the gas flow to a patient's breathing circuit. It may also use the INOblender for backup.The target 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 the secondary targeted clinical setting is the transport of neonates.	explained elsewhere in the labeling.The NOxBOXi system allows adjustable NO gas flow rates for the backup delivery mode.Indications for both devices follow the respective drug labeling for nitric oxide (currently indicated for use with neonates).
NO administration	NO blended with O₂ in the patient's inhalation circuit	NO blended with O₂ in the patient's inhalation circuit	Identical
NO flow rate(sample flow rate)	225 ml/min	250 ml/min	Minor difference, The NOxBOXi system meets its measuring accuracy requirements with a lower sample flow rate from the
ManufacturerTrade Name	Praxair Distribution, Inc.NOxBOXi Nitric Oxide DeliverySystem	INO TherapeuticsINOmax DS	Comparison
			circuit.
NO concentrationprovided	0.0 TO 80ppm	0-80ppm (800ppm cylinder)	Identical
NO monitor	Yes	Yes	Identical
O₂ monitor	Yes	Yes	Identical
Monitoringaccuracy	NO & NO₂ - +/- 2% or 0.2ppm	+/-20% or 2ppm (whichever isgreater)	Different, however,substantiallyequivalent. Thedifference is that theNOxBOXi systemmeasures with moreaccurate specifications.The NOxBOXi uses aclosed loop systemautomatically adjustingthe dose to achieve aset point within +/-2%or 0.2 ppm (whicheveris greater).
NO₂ monitor &alarm	Yes	Yes	Identical
Battery Backupcapability	4 hours without AC power	6 hours without AC power	Different, however,acceptable foremergency usesituations. The batteryis only to be used as abackup in event offacility power loss.Most hospitals havegenerators to providebackup power. In aworst case scenario,the unit can beswitched to manualoverride for gasdelivery withoutmonitoring (purelymechanical).
Complies with ISO10993-1	Yes	Yes	Identical
Electrical SafetyTesting (ISO60601-1 3rd ed)Passed	Yes	Yes	Earlier versions of thepredicate device werecompliant with thisstandard.
EMC Testing (ISO60601-1-2)	Yes	Yes	Earlier versions of thepredicate device werecompliant with thisstandard.
Manufacturer	Praxair Distribution, Inc.	INO Therapeutics	Comparison
Trade Name	NOX BOXi Nitric Oxide DeliverySystem	INOmax DS
Manual bagging &back up system	NOxMIXER®	INOblender®
NO dosing range inmanual mode	0 - 185ppm on 800ppm cylinders	5-80ppm on 800ppm NO; 2.5-40ppm on 400ppm NO	Different, however,substantiallyequivalent. TheNOXBOXi has anexpanded userselectable dose range.
NO dosingAccuracy inmanual mode	± 20% or 2 ppm, whichever is thegreater for NO doses from 5 - 80ppm (800 ppm drug cylinder) andO2 flow rates of 5 - 14 L/min* +/-40% or 4 ppm, whichever isthe greater; for NO doses from 0to < 5 ppm or > 80 to 185 ppm(800 ppm drug cylinder) and O2flow rates of 2 to < 5 L/min or > 14to 25 L/min	+/- 20% indicated or 2 ppm,whichever is greater	Different, however,substantiallyequivalent. TheNOxBOXi has anexpanded userselectable dose range.Similar accuracy for thelimited INOBlenderrange.
NO flow in manualmode	Adjustable 50 – 600 mL/min ofNO/N2	250 mL/min Fixed Flow ofNO/N2	User adjustable flowrange
O2 flow range inmanual baggingmode	2 to 25 L/min of O2	5 to 14 L/min of O2	Different, however,substantiallyequivalent. TheNOXBOxi has anexpanded userselectable flow range.
Oxygen inletpressure	3.5 – 4.5 bar	3-5 bar	Different, however,substantiallyequivalent. Oxygeninlet pressure istypically available inclinical settings.
NO deliverypressure	1.65bar from manual control valve	1.7 to 2.4 bar	Different however,substantially equivalentfor the deliverypressure for neonates.
Manual bagging &back up system	NOxMIXER®	INOblender®
Dimensions	65 mm (W) X 185 mm (H) x 60.8mm (D)	200 mm (W) X 120 mm (H) X110 mm (D) DISS (clampincluded); 200 mm (W) X 120mm (H) X 131 mm (D) NIST(clamp included)	NOxMixer is integratedwith NOxBOXi system
Pre-use set uptime	Instant set-up	4-6 mins (purge and test 2-3mins each)	Different however,substantiallyequivalent. TheNOxBOXi has a reducedsetup time.
Monitoring during	Yes	Yes	Equivalent
Manufacturer	Praxair Distribution, Inc.	INO Therapeutics	Comparison
Trade Name	NOxBOXi Nitric Oxide Delivery System	INOmax DS
manual bagging
Alarms active during bagging	Yes	Yes	Equivalent
Stand alone vs Built-in	Built-in	Stand alone	More compact package
Can also be used as a back-up function	Yes	Yes	Equivalent
Back-up accuracy	$\pm$ 20% or 2 ppm, whichever is the greater for NO doses from 5 - 80 ppm (800 ppm drug cylinder), *$+/-$ 40% or 4 ppm, whichever is the greater; for NO doses from 0 to < 5 ppm or > 80 to 185 ppm (800 ppm drug cylinder)	+/- 20 % indicated or 2 ppm, whichever is greater	Equivalent

Comparison of Characteristics

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9. Non-Clinical Performance Data

Biocompatibility:

NOxBOXi accessories are compatible with human use per FDA guidance document "Use of International Standard ISO 10993-1, "Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process". As was determined to be necessary during the risk management process, these accessories have been tested for biocompatibility as follows:

Cytotoxicity (ISO 10993-5) Irritation (ISO 10993-10) Sensitization (ISO 10993-10)

All biocompatibility tests were performed via direct physical contact with test mediums or through the use of liquid extraction mediums. All tests passed successfully while utilizing these extraction methods.

Gases delivered through the NOxBOXi system were analyzed for the presence of volatile organic compounds(VOC) and particulate matter. Measurement of the resulting VOC concentrations resulted in levels that were three orders of magnitude below OSHA permissible exposure levels. Particulate testing determined that the gas delivered by the NOxBOXi system contained particulate levels well below the EPA's maximum limits for total suspended particulates.

General Safety, Electrical Safety and EMC Testing:

Electrical safety and EMC testing was conducted per the requirements of ISO 60601-1 (30 edition) and ISO 60601-1-2, and all results passed. The respiratory gas monitors were tested per the requirements of ISO 80601-2-55. Applicable symbols from ISO 15223-1 were incorporated into the device labeling.

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The NOxBOXi system has been tested in accordance with the requirements of the FDA's Nitric Oxide Delivery System guidance document. In particular, the following aspects have been tested:

Accuracy of NO delivery Response of NO delivery to external perturbations and user changes Purity of NO drug delivery Acceptable / minimal production of NO2 NO analyzer accuracy NO2 analyzer accuracy Compatibility testing of ventilators listed in the product labeling

Software Verification and Validation:

Software designed to be used with the NOxBOXi Nitric Oxide Delivery System was validated per the requirements of FDA Guidance on Software Contained in Medical Devices and ISO 62304. The software for this device was considered a "Major" level of concern.

10. Usability Testing:

Usability testing of the NOxBOXi Nitric Oxide Delivery System was conducted per the requirements of ISO 62366 and the FDA's guidance document "Applying Human Factors and Usability Engineering to Medical Devices."

11. Clinical Performance Data

There was no clinical testing required to support the substantial equivalency of this medical device as the indications for use and technological characteristics are equivalent to the predicate device.

12. Conclusions/Statement of Substantial Equivalence

The above-described non-clinical data support the substantial equivalence of the device and its hardware, and the software verification and validation and usability testing demonstrate that the NOxBOXi performs as intended in the specified use conditions. The NOxBOXi passed all testing and no different questions of safety or effectiveness were raised. Test results were relied upon to support the claim of substantial equivalence to the 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.”