The Nitronox Plus is intended to provide a mixture of N20/02, on demand, to a conscious, spontaneously breathing patient. The Nitronox Plus is designed for use with adult and pediatric patients and is not intended to be used with infants or neonates.

Device Description

The Nitronox Plus is a portable "on demand" analgesia system used to deliver a mixture of nitrous oxide and oxygen gases to a conscious, spontaneously breathing patient. The device is designed for use with adult and pediatric patients and is not intended to be used with infants or neonates. It is only for use in a healthcare setting by healthcare professionals. The Nitronox Plus is available in three models which differ only in adjustability and maximum ratio of nitrous oxide that can be delivered. The Nitronox Plus features a 0-70% N2O adjustable model, 0-50% N2O adjustable model, and 50% N2O/50% O2 fixed model.

The Nitronox Plus is a pneumatic system. Oxygen and nitrous oxide are supplied to the device through flexible hoses. Inlet gas is regulated and equalized through the use of an oxygen piloted dual diaphragm regulator. The inlet pressure of both gases and the mixed gas pressure are displayed on the front panel of the device through the use of pressure gauges. The device is designed to function with a medical breathing circuit and face mask or mouthpiece accessory.

Delivery of mixed gas starts with a patient's demand; upon inhalation through a face mask or mouthpiece, a demand valve opens and supplies mixed gas to the patient through the connected Medical Breathing Circuit. In adjustable models, the healthcare professional is able to set the desired concentration through the use of a control knob on the front panel. Mixed gas is supplied through the breathing circuit until inhalation ceases.

The Nitronox Plus contains several safety features. Pneumatically powered alarms for both gas inlets alert the user when either gas supply begins to deplete. The device will also maintain delivery of the set concentration with depleting oxygen pressure. Once the oxygen pressure drops below a certain threshold, the device will allow ambient air to be delivered through an Emergency Air Intake valve. The device also features a key lock to control the nitrous oxide gas supply, allowing healthcare professionals to prevent unauthorized use of the device.

AI/ML Overview

The provided text describes the safety, operational, and performance requirements for the Nitronox Plus breathing gas mixer, but it does not provide a specific table of acceptance criteria or detailed results of a study proving the device meets those criteria, especially at the level of detail requested for AI/diagnostic studies. Instead, it broadly states that performance testing was conducted and demonstrates the device meets "all design input requirements."

Therefore, many of the requested details cannot be extracted from this document, as it focuses on establishing substantial equivalence to a predicate device rather than presenting a detailed performance study with specific metrics, sample sizes, and ground truth methodologies relevant to AI or diagnostic devices.

However, I can provide what can be inferred from the text based on its content about non-clinical performance testing.

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

The document does not provide a specific table of quantitative acceptance criteria or detailed reported device performance values. It generally states that "performance testing was conducted to verify performance characteristics, safety features, capabilities compared to the predicate device, and biocompatibility." The "reported device performance" is essentially that the device "meets all design input requirements, including functional, operational, and performance requirements."

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

This information is not explicitly provided in the document. The testing described is "non-clinical performance testing," which typically involves bench testing, engineering verification, and validation, rather than clinical studies with human subjects or data sets.

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 applicable and is not provided. The "ground truth" in this context would likely refer to engineering specifications and measurements, not expert consensus on diagnostic images.

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

This information is not applicable and is not provided. Adjudication methods are typically used in clinical trials or studies involving expert review, which is not the type of testing described here.

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

No such study was conducted or is mentioned in the document. This is a breathing gas mixer, not an AI or diagnostic imaging device.

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 physical breathing gas mixer, not a software algorithm. Its "performance" is inherently standalone in that it functions according to its design specifications.

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

The "ground truth" for this device would be established through engineering specifications, validated test methods, and measurement standards for gas mixtures, pressure regulation, alarm functionality, and other specified device characteristics. The document implies that these standards were used in the "performance testing."

8. The sample size for the training set

This information is not applicable as the device is not an AI model requiring a training set.

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

This information is not applicable as the device is not an AI model.

Summary of available information regarding the acceptance criteria and study:

The document states that "performance testing was conducted to verify performance characteristics, safety features, capabilities compared to the predicate device, and biocompatibility; validate reprocessing activities; and ensure usability of the device to meet patient needs when used as intended."

The study proving the device meets its acceptance criteria is referred to as "non-clinical performance testing."

Acceptance Criteria (Implied): The device "meets all design input requirements, including functional, operational, and performance requirements." These requirements would likely include specifications for N2O/O2 mixture accuracy, pressure regulation (45-60 psi input, low pressure mixed gas output), alarm activation thresholds (e.g., N2O/O2 input below 35 psi), demand valve responsiveness, and the proper functioning of safety features like the O2 piloted system, DISS fittings, and the Emergency Air Intake Valve.
Reported Device Performance: "The results of performance testing demonstrate that the Nitronox Plus meets all design input requirements..." and "Performance testing supports the conclusion that the subject device is as safe and effective as the predicate device, and therefore the two devices are substantially equivalent."

This is a substantial equivalence (510(k)) submission, which focuses on demonstrating that a new device is "as safe and effective" as a legally marketed predicate device, rather than providing detailed clinical efficacy trial data, which would be typical for a PMA submission or for AI/diagnostic devices. The "study" here is a set of "non-clinical performance tests" that show the device functions according to its engineering and safety specifications, aligning with the predicate device's performance profile (where applicable, and noting differences and new features).

Summary

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April 22, 2021

Parker Hannifin % Dave Yungvirt CEO Third Party Review Group, LLC 25 Independence Blvd Warren, New Jersey 07059

Re: K202480

Trade/Device Name: Nitronox Plus Regulation Number: 21 CFR 868.5330 Regulation Name: Breathing gas mixer Regulatory Class: Class II Product Code: BZR Dated: August 26, 2020 Received: August 28, 2020

Dear Dave Yungvirt:

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,

for 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) K202480

Device Name Nitronox Plus

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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X Prescription Use (Part 21 CFR 801 Subpart D)

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

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న్. 510(k) Summary

Parker Hannifin Nitronox Plus (per 21CFR 807.92)

5.1. Submitter/510(k) Holder

Parker Hannifin CorporationPrecision Fluidics Division245 Township Line RoadHatfield, Pennsylvania 19440Phone: 215-723-4000	Contact: Andrew Ellinger,Product Development EngineerContact Phone: 215-660-8175Contact Email: andrew.ellinger@parker.comDate Prepared: May 1, 2020
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5.2. Device Name

Proprietary Name:	Nitronox Plus
Common Name:	Breathing gas mixer
Classification Name:	Mixer, breathing gases, anesthesia inhalation
Classification Regulation:	21 CFR 868.5330
Classification Panel:	Anesthesiology
Product Code:	BZR
Device Class:	Class II

5.3. Predicate Device

Nitronox Pre-Set 50/50 Nitrous Oxide/Oxygen Gas Mixer (K760766)

5.4. Device Description

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5.5. Indications for Use

The Nitronox Plus is intended to provide a mixture of N20/O2, on demand, to a conscious, spontaneously breathing patient. The Nitronox Plus is designed for use with adult and pediatric patients and is not intended to be used with infants or neonates.

The Indications for Use statement for the Nitronox Plus is not identical to the predicate device; however, the differences do not alter the intended therapeutic use of the device. Modifications made to enhance gas delivery functionality do not significantly change the key functional technology and operational characteristics of the device, nor do they affect the safety and effectiveness of the device relative to the predicate. Both the subject and predicate devices are intended to deliver mixtures of N20/02, on demand, to a conscious, spontaneously breathing patient.

Summary of Technological Characteristics Compared to the Predicate Device 5.6.

The Nitronox Plus (subject device) is a redesigned version of the Nitronox HD originally cleared by FDA under submission K760766 (predicate device). The key technological characteristics of the Nitronox Plus are based on well-established technology that uses springs, diaphragms, valves, orifices, and other pneumatic mechanisms to regulate the pressure and flow of gases. The subject device is similar to the predicate device regarding:

Force-balancing system consisting of diaphragms, springs, and poppet valves ●
Gas mixing through tapered valve stems and orifices ●
Pneumatic "whistle" alarms
Bourdon tube gauges ●
Demand valve to only deliver gas upon patient inhalation

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The major technological differences between the subject device and predicate device include:

Adjustable mixture ratio .
. Low inlet pressure alarms
Emergency air intake valve .
. Key lock feature

A summary comparison of the subject and predicate devices is provided below:

Characteristic	Subject:Nitronox Plus	Predicate:Nitronox (K760766)	Comparison
Intended Use	Provide a mixture of N2O/O2, ondemand, to a conscious,spontaneously breathing patient. TheNitronox Plus is designed for usewith adult and pediatric patients andis not intended to be used withinfants or neonates.	Provide 50/50% N2O/O2 mixture, ondemand, to a conscious,spontaneously breathing patient.	Similar
TargetPopulation	Adult and pediatric patients. Notintended to be used with infants orneonates	Spontaneous breathing patientsrequiring pain relief.	Similar
Prescription orOver-the-Counter Use	Prescription Use	Prescription Use	Same
Anatomical Site	Gas is to be inhaled through themouth and nose region.	Gas is to be inhaled through themouth and nose region.	Same
Where used	To be used by healthcareprofessionals in a healthcare setting.	Dentistry, Emergency Departments,Ambulances, Obstetrics,Physiotherapy. Nursing. SpecialistProcedures, and Podiatry.	Similar
Operatingprinciple	Pneumatic, demand flow system.	Pneumatic, demand flow system.	Same
Energy used	Compressed oxygen/nitrous oxidegas.	Compressed oxygen/nitrous oxidegas.	Same
Energydelivered	Low pressure mixed gas.	Low pressure mixed gas.	Same
Gas inputpressure	45-60 psi.	45-60 psi.	Same
Gas regulationmechanism	Oxygen Piloted Regulator with dualdiaphragms.	Oxygen Piloted Regulator with dualdiaphragms.	Same
Gas delivery	Proportional to patient's demand.	Proportional to patient's demand.	Same
Gas mixing	Oxygen and nitrous oxide areequalized and mixed at variableratios.	Oxygen and nitrous oxide areequalized and mixed at a fixed 50%ratio.	Different
Alarms	Audible alarm sounds when:- N2O input is below 35 psi;- O2 input is below 35 psi.	Audible alarm is triggered if oxygenmixture pressure rises above 40 psi.	Different
Security feature	Key Lock allows healthcareprovider to turn device ON/OFF; inthe "OFF" position device will notdeliver nitrous oxide gas; with thekey turned in the "ON" position,mixed gas can be supplied.	None.	New Feature
Characteristic	Subject:Nitronox Plus	Predicate:Nitronox (K760766)	Comparison
Accessories	- Medical Breathing Circuit;- Face mask;- Mouth Piece;- Oxygen & nitrous oxide supplyhose;- Oxygen & nitrous oxide;- E-stand mobile cart;- Two Cylinder Cart;- Wall arm mount;	- Medical Breathing Circuit;- Face mask;- Mouth Piece;- Oxygen & nitrous oxide supplyhose;- Oxygen & nitrous oxide;- E-stand mobile cart;- Two Cylinder Cart;- Wall arm mount;	Same
Pressureregulation	Force-balanced system ofdiaphragms/poppets/springs	Force-balanced system ofdiaphragms/poppets/springs	Same
Gas mixingmechanism	Adjustable dual stem/orifice	Factory set dual stem/orifice	Different
Demandmechanism	Demand Valve	Demand Valve	Same
Gauge type	Bourdon Tube	Bourdon Tube	Same
Alarm type	Pneumatic whistle	Pneumatic whistle	Same
Safety Features	O2 Piloted System: Shut off mixeroutput if O2 pressure drops.	O2 Piloted System: Shut off mixeroutput if O2 pressure drops.	Same
	DISS fittings to preventmisconnection of gas supply.	DISS fittings to preventmisconnection of gas supply.	Same
	Activated only via patientinspiratory effort (self-administration principle).	Activated only via patientinspiratory effort (self-administration principle).	Same
	In the event of N2O supply failure,100% O2 will be supplied.	In the event of N2O supply failure,100% O2 will be supplied.	Same
	Dual diaphragms prevent reversegas flow between supplies.	Dual diaphragms prevent reversegas flow between supplies.	Same
	Audible alarm for low inlet pressure.	Audible alarm for increased mixpressure.	Different
	Emergency Air Intake Valve, if O2pressure is lost patient can breatheambient air.	None.	New Feature
	Key lock system preventsunauthorized use of device.	None.	New Feature

Side-by-Side Comparison of the Subject and Predicate Devices

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Summary of Non-clinical Performance Testing as Basis for Substantial 5.7. Equivalence

The results of performance testing demonstrate that the Nitronox Plus meets all design input requirements, including functional, operational, and performance requirements. Performance testing was conducted to verify performance characteristics, safety features, capabilities compared to the predicate device, and biocompatibility; validate reprocessing activities; and ensure usability of the device to meet patient needs when used as intended. The results of the performance testing support the conclusion that the subject device is substantially equivalent to the predicate device.

Risk management processes were applied throughout product development. Results of the comprehensive risk analysis conclude that the benefits associated with the design modifications for new and enhanced safety systems exceed any residual risk. The remaining risks are acceptable when weighed against the benefits provided to patients when using the device. None of the residual risks outweigh the benefits of using the Nitronox Plus system for its intended use.

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5.8. Conclusions

The indications for use, principles of operation, and technological characteristics of the subject device are similar to the predicate device. Differences between the subject and predicate devices are limited to minor differences in the technology used to adjust the mixture ratio, triggering conditions of audible alarms, and addition of the emergency air intake and key lock safety features. Performance testing supports the conclusion that the subject device is as safe and effective as the predicate device, and therefore the two devices are substantially equivalent.

Regulation Number and Section

§ 868.5330 Breathing gas mixer.

(a)
Identification. A breathing gas mixer is a device intended for use in conjunction with a respiratory support apparatus to control the mixing of gases that are to be breathed by a patient.(b)
Classification. Class II (performance standards).