The Evolve DS (delivery system) delivers INOMAX® (nitric oxide for inhalation) therapy gas into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath. It uses a specially designed Injector Module, which enables tracking of the gas delivery system waveforms and the delivery of a synchronized and proportional dose of NO. It may be used with ventilators and respiratory care devices for which the Evolve DS has been validated. The Evolve DS provides continuous integrated monitoring of inspired NO2 and NO with a comprehensive alarm system. The Evolve DS also provides monitoring and alarms for the drug delivery system.

The Evolve DS incorporates a battery that provides up to 4 hours of uninterrupted NO delivery in the absence of external power. The Evolve DS also incorporates an integrated electronic blender that functions as a backup delivery device to provide an adjustable INOmax dose with user supplied oxygen to a manual resuscitator or gas delivery system. The electronic blender incorporates a separate control and delivery pathway that serves as a redundant mechanism for nitric oxide delivery in the event of a main system fault.

The Evolve DS 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 Evolve DS is indicated for a maximum of 14 days use. The primary targeted clinical setting is the Neonatal Intensive Care Unit (NICU), and secondary targeted clinical setting is the transport of neonates.

Device Description

The EVOLVE Nitric Oxide (NO) Delivery System (DS) is used for administration and monitoring of INOMAX (nitric oxide for inhalation). It is comprised of a main delivery device (EVOLVE), an electronic blender (eINOblender) for backup use, and a Cart which holds the EVOLVE as well as INOMAX drug cylinders, an oxygen cylinder and miscellaneous parts.

The EVOLVE Nitric Oxide Delivery System utilizes Technology component technology to deliver Nitric Oxide gas to the patient. The components consist of a main delivery device (EVOLVE), an electronic blender (eINOblender) for backup use, and a Cart which holds the EVOLVE as well as INOMAX drug cylinders, an oxygen cylinder and miscellaneous parts. In this revision of the EVOLVE Nitric Oxide Delivery System, the changes to the device includes the labeling for compatibility with respiratory care devices.

AI/ML Overview

The provided FDA document describes a 510(k) premarket notification for the EVOLVE Nitric Oxide Delivery System. This submission is for an updated version of a previously cleared device (K240410 and K222930), primarily focusing on expanded labeling for compatibility with additional ventilator and breathing devices.

Therefore, the document does not contain information about acceptance criteria and a study that proves the device meets those criteria in the context of device performance, as it pertains to a labeling update for compatibility. Clinical studies were explicitly stated as "not applicable to this submission."

Here's a breakdown of what can be extracted based on your request, and what cannot:

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

This information is not provided in the document. The filing is for a change in labeling for compatibility with more ventilator devices, not for demonstrating new performance criteria for the core device. It implicitly relies on the original clearance for the device's performance specifications.

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

Sample size for test set: Not explicitly stated as a numerical value for patients or cases. The "test set" in this context refers to the additional ventilator and breathing devices with which compatibility was tested.
Data Provenance: The testing was "conducted across all platforms to demonstrate that the EVOLVE Nitric Oxide Delivery System performs within published specifications." This suggests laboratory or bench testing rather than clinical data from a specific geographic region or a prospective/retrospective study on human subjects.

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

This information is not provided. The testing described is focused on the device's functional performance and compatibility with other medical equipment, not on clinical interpretations that would require expert consensus for ground truth.

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

This information is not provided, as the nature of the "test set" does not involve clinical judgment requiring adjudication.

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 information is not applicable/provided. The device described is a nitric oxide delivery system, not an AI-assisted diagnostic or therapeutic device that would involve human readers or image interpretation.

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

This information is not applicable/provided for the same reasons as above. The device doesn't involve an algorithm in the sense of AI for diagnostic or interpretive tasks.

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

The "ground truth" for the compatibility testing appears to be the published specifications of the EVOLVE Nitric Oxide Delivery System and the functional operation of the connected ventilator devices. The testing aimed to demonstrate that the EVOLVE system "performs within published specifications" when used with the additional ventilators.

8. The sample size for the training set:

This is not applicable/provided. The submission is not for a machine learning or AI-based device that would typically have a training set.

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

This is not applicable/provided.

Summary of what is available from the document:

Device Name: EVOLVE Nitric Oxide Delivery System
Purpose of Submission: Updated labeling for compatibility with additional ventilator and breathing devices.
Testing Conducted: "Ventilator / Gas Delivery System Validation Test Protocol" was used to validate hazard mitigation and demonstrate performance within published specifications across various ventilator platforms. This was the same protocol used in previous clearances (K222930 and K240410).
Clinical Studies: Explicitly stated as "not applicable to this submission."
Predicate Device: EVOLVE Nitric Oxide Delivery System (K240410). The current device is considered substantially equivalent.

In conclusion, the supplied document does not describe the types of performance studies (e.g., diagnostic accuracy, clinical effectiveness) and associated acceptance criteria that would typically involve many of the points in your request. Instead, it focuses on technical compatibility validation for a medical device.

Summary

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January 3, 2025

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services seal on the left and the FDA acronym and name on the right. The FDA acronym is in a blue box, and the full name, "U.S. Food & Drug Administration," is in blue text.

Mallinckrodt Manufacturing LLC Jennifer Brett Senior Manager, Devices Global Regulatory Affairs 6603 Femrite Drive Madison, Wisconsin 53718

Re: K242578

Trade/Device Name: EVOLVE Nitric Oxide Delivery System Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: Class II Product Code: MRN, MRP, MRP, MRQ Dated: December 6, 2024 Received: December 6, 2024

Dear Jennifer Brett:

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 (the 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 available 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.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 medical devices and radiation-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-regulatory

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assistance/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,

Bradley Q. Quinn -S

Bradley Quinn Assistant Director DHT1C: Division of Anesthesia, Respiratory, and Sleep 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) K242578

Device Name EVOLVE Nitric Oxide Delivery System

Indications for Use (Describe)

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

In accordance with 21 CFR 807.92 the following summary of information is provided:

Submitter Information
Date:	01 Jan, 2025
Company:	Mallinckrodt Manufacturing, LLC6603 Femrite DriveMadison, Wisconsin 53718
Contact Person:	Jennifer BrettSenior Manager, Devices Global Regulatory Affairs
Email:	Jennifer.Brett@sbiopharma.com
Telephone:	+353 87 2851461
Secondary Contact Person:	David TruebloodSr. Director, Regulatory Affairs, Devices
Email:	David.Trueblood@sbiopharma.com
Telephone:	608-320-2755

Identification of the Device

Device Trade Name:	EVOLVE Nitric Oxide Delivery System
Common Name:	Nitric Oxide Administration Apparatus (primary)Nitric Oxide AnalyzerNitrogen Dioxide Analyzer
Classification Name:	Apparatus, Nitric Oxide Delivery, or Apparatus, NitricOxide Backup Delivery
Device Classification:	Class II – 21 CFR 868.5165
Product Code:	MRN (Primary), MRQ, MRP

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Predicate Device(s) K240410

Description of Device The EVOLVE Nitric Oxide (NO) Delivery System (DS) is used for administration and monitoring of INOMAX (nitric oxide for inhalation). It is comprised of a main delivery device (EVOLVE), an electronic blender (eINOblender) for backup use, and a Cart which holds the EVOLVE as well as INOMAX drug cylinders, an oxygen cylinder and miscellaneous parts.

Intended Use The Evolve DS (delivery system) delivers INOMAX® (nitric oxide for inhalation) therapy gas into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath. It uses a specially designed Injector Module, which enables tracking of the gas delivery system waveforms and the delivery of a synchronized and proportional dose of NO. It may be used with ventilators and respiratory care devices for which the Evolve DS has been validated. The Evolve DS provides continuous integrated monitoring of inspired NO2 and NO with a comprehensive alarm system. The Evolve DS also provides monitoring and alarms for the drug delivery system.

The Evolve DS incorporates a battery that provides up to 4 hours of uninterrupted NO delivery in the absence of external power. The Evolve DS also incorporates an integrated electronic blender that functions as a backup delivery device to provide an adjustable INOmax dose with user supplied oxygen to a manual resuscitator or gas delivery system. The electronic blender incorporates a separate control and delivery pathway that serves as a redundant mechanism for nitric oxide delivery in the event of a main system fault.

The Evolve DS must only be used in accordance with the indications, contraindications, 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 Evolve DS is indicated for a maximum of 14 days use. The primary targeted clinical setting is the Neonatal Intensive Care Unit

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(NICU), and secondary targeted clinical setting is the transport of neonates.

Determination of Substantial Equivalence

The modified EVOLVE Nitric Oxide Delivery System has the same intended use as the previously cleared EVOLVE Nitric Oxide Delivery System (K240410). All features are identical except those described in the table below.

Feature /Specification	EVOLVE Nitric OxideDelivery SystemK240410	EVOLVE Nitric Oxide Delivery Systemwith additional ventilator and breathingdevices
Labeling forcompatibility withventilator devices	A variety of neonatal,adult/ped, high frequencyand anesthesia ventilators,nasal CPAP and nasal highflow cannulas.	Additional ventilator devices and breathingdevices include:Airon pNeuton mini Coviden Newport HT70 Plus Dräger 3000/3000 plus Dräger Savina 300 Fisher & Paykel Healthcare Airvo 3 GE Healthcare Carescape R860 GE Healthcare Avance CS2/Aisys CS2 Getinge Servo-air 4.0 Nihon Kohden NKV-330 Smiths Medical ParaPAC 200/200D Vyaire Avea Vyaire Bellavista 1000/1000e Vyaire ReVel

Comparison to Predicate Device

Summary of Non-Clinical Tests

In the original EVOLVE Nitric Oxide Delivery System 510(k) [K222930], the Ventilator / Gas Delivery System Validation Test Protocol was accepted, and the outcomes were used as

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justification on clearance of the submission. The Ventilator / Gas Delivery System Validation Test Protocol was used to validate the hazards identified from risk input were mitigated. This same protocol was subsequently used for ventilator validations as part of K240410 and this submission. Testing was conducted across all platforms to demonstrate that the EVOLVE Nitric Oxide Delivery System performs within published specifications. Ultimately, the requirements necessary for the operation of the EVOLVE Nitric Oxide Delivery System passed.

Summary of Clinical Tests

This section is not applicable to this submission. The subject of this premarket submission, EVOLVE Nitric Oxide Delivery System with updated labeling to interface with additional ventilator and breathing devices, did not require clinical studies to support substantial equivalence.

Conclusion

Mallinckrodt Manufacturing, LLC considers the EVOLVE Nitric Oxide Delivery System to be as safe and as effective as the predicate device, with performance substantially equivalent 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.”