The AeroNOx 2.0 is intended to provide a constant controlled concentration of nitric oxide in breathing gas by delivering a constant controlled flow of nitric oxide into the inspiratory limb of a mechanical ventilator that operates using a continuous constant flow of fresh gas into the inspiratory limb of the ventilator. The AeroNOx 2.0 is also intended to be used with a flow inflating manual ventilator (an AeroNOx 2.0 accessory), by introducing controlled flows of nitric oxide into the fresh gas flow to the manual ventilator. It is also intended to monitor nitric oxide, nitrogen dioxide, and oxygen concentrations in the breathing gas. The AeroNOx 2.0 is intended to be used within a hospital or during air or ground transport outside the hospital.

Device Description

The AeroNOx 2.0 nitric oxide delivery system is specifically designed for the transmission and control of gaseous nitric oxide (NO) in parts per million (ppm) concentrations. It is divided into two main components: the delivery component and an analysis component. These two components are mounted into a single enclosure. The delivery component is designed to deliver a constant flow of nitric oxide gas into the main gas stream of a constant flow ventilator or a modified flow inflating manual resuscitator (see "AeroNOx Bagger" and "INOstat Bagger" below). The nitric oxide gas is titrated into the ventilator's gas delivery tubing at a point at least 30cm upstream of the gas analysis port to ensure adequate gas mixing prior to patient delivery. The analysis component of the AeroNOx 2.0 is designed to measure nitric oxide, nitrogen dioxide and oxygen from the ventilator tubing or flow inflating manual resuscitator on the inspiratory side, prior to patient administration. The analysis system consists of one nitric oxide electrochemical cell, one nitrogen dioxide electrochemical cell, one galvanic oxygen sensor, and a pump to draw the gas sample from the ventilator's bulk gas flow for analysis within the block that mounts sensors.

AI/ML Overview

The provided text is a 510(k) summary for the AeroNOx 2.0 Nitric Oxide Titration & Monitoring System. It describes a device modification submission, specifically adding compatibility with more ventilators. This is not a submission for a new AI/ML-driven medical device, and as such, the typical acceptance criteria and study designs associated with AI/ML performance (like MRMC studies, ground truth establishment with experts, data provenance for AI training/test sets) are not applicable to this document.

The "acceptance criteria" here refer to the device meeting performance requirements with the newly compatible ventilators, ensuring substantial equivalence to the predicate device.

Here's how to address the request based on the provided document:

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

The document broadly states that the device "met all the performance requirements as outlined above" but does not detail specific quantitative acceptance criteria (e.g., accuracy, precision ranges for gas concentrations) or the numerical results of those tests. This type of information would typically be in a more detailed test report, not usually fully replicated in a 510(k) summary.

Acceptance Criteria (Implied from the document):

Parameter	Acceptance Criteria (Implied)	Reported Device Performance
Ventilator Compatibility	Device functions correctly and safely with additional ventilators.	"The AeroNox 2.0 met all the performance requirements as outlined above."
Performance (e.g., NO, NO2, O2 monitoring, NO titration)	Maintain established performance from the predicate device.	"The AeroNox 2.0 met all the performance requirements as outlined above."
Safety	No new safety concerns introduced with the modification.	Implied by "found to be substantially equivalent to the predicate devices."

2. Sample size used for the test set and the data provenance:

Sample Size: Not explicitly stated. The document only mentions "Ventilator Compatibility Testing." It does not specify how many different ventilators were tested, nor the duration or number of trials for each.
Data Provenance: This is a physical device test, not a data-driven AI test. Therefore, data provenance in the context of "country of origin of the data, retrospective or prospective" is not directly applicable. The testing was prospective, as it was conducted to support this specific 510(k) submission.

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 question is not applicable. This is a hardware/system performance test, not a clinical study involving human expert interpretation of medical images or data. "Ground truth" for this device would refer to known gas concentrations in the test setup, measured by calibrated reference instruments. Experts are not involved in establishing this type of ground truth.

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

This question is not applicable. Adjudication methods like 2+1 or 3+1 are used in clinical studies where human readers provide interpretations (e.g., radiologists interpreting images) and consensus is needed to establish ground truth. This is a bench test of a medical device's functional performance.

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

This question is not applicable. MRMC studies are specific to evaluating the impact of AI/ML algorithms on human reader performance, typically in diagnostic imaging. This submission concerns a physical medical device (nitric oxide delivery and monitoring system), not an AI algorithm assisting human readers.

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

This question is not applicable. The AeroNOx 2.0 is a physical device, not a standalone algorithm. While it contains internal algorithms for controlling gas delivery and monitoring, the "standalone performance" concept usually refers to an AI algorithm's diagnostic or predictive accuracy when operating independently of human clinicians. The document describes bench testing of the system's overall functionality.

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

For this device, the "ground truth" would be established by reference instruments or known gas mixtures used during the bench testing. For example, if testing NO concentration accuracy, the "ground truth" would be the precisely known concentration of NO in the test gas, measured by a highly accurate, calibrated lab-grade gas analyzer. It is not expert consensus, pathology, or outcomes data.

8. The sample size for the training set:

This question is not applicable, and potentially misleading. The term "training set" refers to data used to train AI/ML models. This device is a traditional electromechanical medical device, not an AI/ML product. It does not have a "training set" in the machine learning sense. Any calibration data used by the sensors or control systems would be part of the device's inherent design and calibration process, not a "training set."

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

This question is not applicable for the same reasons as #8.

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.

International Biomedical Amy Pieper Director of Regulatory Affairs 8206 Cross Park Drive Austin, Texas 78754

Re: K193481

Trade/Device Name: AeroNOx 2.0 Nitric Oxide Titration & Monitoring System Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: Class II Product Code: MRN Dated: February 7, 2020 Received: February 10, 2020

Dear Amy Pieper:

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 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for

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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 (QS) 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.

Todd Courtney Assistant Director DHT1C: Division of ENT, 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) K193481

Device Name

AeroNOx 2.0 Nitric Oxide Titration & Monitoring System

Indications for Use (Describe)

The AeroNOx 2.0 is intended to be used within a hospital or during air or ground transport outside the hospital.

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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Special 510(k): Device Modification AeroNOx 2.0 Nitric Oxide Titration & Monitoring System

K193481

510(k) SUMMARY

Submitter Information:

International Biomedical 8206 Cross Park Drive Austin, TX 78754 U.S.A.

Regulatory Affairs Contact: Amy Pieper Director of Regulatory Affairs (512) 873-0033 - phone (512) 873-9090 - fax

Date Summary Prepared: December 13, 2019

Device Identification:

Trade Name: AeroNOx 2.0 Nitric Oxide Titration & Monitoring System Common Name: Nitric Oxide Delivery System Regulatory Class: II Regulation: 868.5165 Product Code: MRN Panel: Anesthesiology

Predicate Device:

AeroNOx 2.0 Nitric Oxide Titration & Monitoring System (K093260)

Device Description:

The delivery component is designed to deliver a constant flow of nitric oxide gas into the main gas stream of a constant flow ventilator or a modified flow inflating manual resuscitator (see "AeroNOx Bagger" and "INOstat Bagger" below). The nitric oxide gas is titrated into the ventilator's gas delivery tubing at a point at least 30cm upstream of the gas analysis port to ensure adequate gas mixing prior to patient delivery.

The analysis component of the AeroNOx 2.0 is designed to measure nitric oxide, nitrogen dioxide and oxygen from the ventilator tubing or flow inflating manual resuscitator on the inspiratory side, prior to patient administration. The analysis system consists of one nitric oxide electrochemical cell, one nitrogen dioxide electrochemical cell, one galvanic oxygen sensor, and a pump to draw the gas sample from the ventilator's bulk gas flow for analysis within the block that mounts sensors.

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K193481

Special 510(k): Device Modification AeroNOx 2.0 Nitric Oxide Titration & Monitoring System

In addition, two variations of a modified flow inflating manual resuscitator are available to use as back-up systems in the event of ventilator failure. AeroNOx failure, or a combination of these two. Both resuscitators are disposable, single patient use devices. These are described below:

1. The "AeroNOx Bagger" flow inflating manual resuscitator is designed for use with the AeroNOx. It can be used completely independent of the ventilator.
1. The "INOstat Bagger" flow inflating manual resuscitator is designed to be used in conjunction with a regulator with a fixed output flow in order to supply a constant nitric oxide dose completely independent of the AeroNOx and ventilator.

Intended Use:

The AeroNOx 2.0 is intended to provide a constant controlled concentration of nitric oxide in breathing gas by delivering a constant controlled flow of nitric oxide into the inspiratory limb of a mechanical ventilator that operates using a continuous constant flow of fresh gas into the inspiratory limb of the ventilator. The AeroNOx 2.0 is also intended to be used with a flow inflating manual ventilator (an AeroNOx accessory), by introducing controlled flows of nitric oxide into the fresh gas flow to the manual ventilator. It is also intended to monitor nitric oxide, nitrogen dioxide, and oxygen concentrations in the breathing gas. The AeroNOx 2.0 is intended to be used within a hospital or during air or ground transport outside the hospital.

Substantial Equivalence:

The AeroNOx 2.0 is substantially equivalent to the AeroNOx 2.0 Nitric Oxide Titration & Delivery System that is currently marketed with regards to intended use, safety and effectiveness.

The intended use of the AeroNOx 2.0 is unchanged from the predicate device

	Proposed (K193481)	Predicate
	AeroNOx 2.0 Nitric Oxide Titration &Monitoring System	K093260/A001 AeroNox 2.0 Nitric OxideTitration & Monitoring System
Indications forUse	The AeroNOx 2.0 is intended to provide aconstant controlled concentration of nitricoxide in breathing gas by delivering aconstant controlled flow of nitric oxideinto the inspiratory limb of a mechanicalventilator that operates using acontinuous constant flow of fresh gas intothe inspiratory limb of the ventilator. TheAeroNOx 2.0 is also intended to be usedwith a flow inflating manual ventilator(an AeroNOx accessory), by introducingcontrolled flows of nitric oxide into the	The AeroNOx 2.0 is intended to provide aconstant controlled concentration of nitricoxide in breathing gas by delivering aconstant controlled flow of nitric oxide intothe inspiratory limb of a mechanicalventilator that operates using a continuousconstant flow of fresh gas into theinspiratory limb of the ventilator. TheAeroNOx 2.0 is also intended to be usedwith a flow inflating manual ventilator (anAeroNOx accessory), by introducingcontrolled flows of nitric oxide into the

	fresh gas flow to the manual ventilator. It is also intended to monitor nitric oxide, nitrogen dioxide, and oxygen concentrations in the breathing gas. The AeroNOx 2.0 is intended to be used within a hospital or during air or ground transport outside the hospital.	fresh gas flow to the manual ventilator. It is also intended to monitor nitric oxide, nitrogen dioxide, and oxygen concentrations in the breathing gas. The AeroNOx 2.0 is intended to be used within a hospital or during air or ground transport outside the hospital.
Environment for Use	Hospital or Air/Ground Transport	Hospital or Air/Ground Transport
Patient Population	Neonatal	Neonatal
Prescriptive	Yes	Yes
Patient Connection	None	None
	NO Sensor: Electro-chemical Sensor integrated into device	NO Sensor: Electro-chemical Sensor integrated into device
Operation Characteristics	NO2 Sensor: Electro-chemical Sensor integrated into device	NO2 Sensor: Electro-chemical Sensor integrated into device
	O2 Sensor: Galvanic Sensor integrated into device	O2 Sensor: Galvanic Sensor integrated into device
Inlet Pressure	14 to 155 Bar	14 to 155 Bar
Outlet Pressure/Connection Type	1.7 to 2.4 Bar/CGA 626	1.7 to 2.4 Bar/CGA 626
Power Rating	100-240 VAC @ 50/60 Hz, 3A	100-240 VAC @ 50/60 Hz, 3A
D/C Battery Backup	Yes	Yes
Electrical Safety	IEC 60601-1IEC 60601-1-2IEC 60601-1-6IEC 60601-1-8IEC 60601-1-12	IEC 60601-1IEC 60601-1-2IEC 60601-1-6IEC 60601-1-8IEC 60601-1-12
Case (Exterior) Materials	Plastic (Cast Urethane)	Plastic (Cast Urethane)
Internal Airway Path Materials	Tygon tubing; stainless steel	Tygon tubing; stainless steel
Accessory Materials	Polypropylene Tubing; Tygon tubing; Stainless Steel Hose/Regulator	Polypropylene Tubing; Tygon tubing; Stainless Steel Hose/Regulator

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Page 3 of 4

K193481 Special 510(k): Device Modification AeroNOx 2.0 Nitric Oxide Titration & Monitoring System

Modification:

The modification is to add additional ventilators to the list of approved ventilators with which the AeroNOx 2.0 can be used. No device modifications have been made from the predicate device. AeroNOx 2.0 has the same fundamental scientific technology and intended use as the predicate device.

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K193481

Special 510(k): Device Modification AeroNOx 2.0 Nitric Oxide Titration & Monitoring System

Bench Testing:

The following tests were performed based on the labeling modification to add additional ventilators to the Operator's Manual.

. Ventilator Compatibility Testing
The AeroNox 2.0 met all the performance requirements as outlined above and thus can be found to be substantially equivalent to the predicate devices.

Conclusion:

The modified AeroNOx 2.0 has the following similarities to the previous AeroNOx 2.0 model that already has 510(k) clearance:

. The same intended use
Use the same operating principle ●
Incorporate the same basic design and electronic circuitry ●
Incorporate the same materials ●

In summary, the AeroNOx 2.0 is substantially equivalent to the AeroNOx Nitric Oxide Titration & Delivery System that is currently marketed with regards to intended use, safety and effectiveness.

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.”