(106 days)
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 (NICU), and secondary targeted clinical setting is the transport of neonates.
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.
This submission is for an updated labeling for compatibility with additional ventilator and breathing devices for the EVOLVE Nitric Oxide Delivery System, not a new device or a software-driven diagnostic. Therefore, the detailed information about acceptance criteria, device performance, sample sizes, expert involvement, and ground truth establishment typically required for AI/ML device studies is not available in this document.
The document primarily focuses on demonstrating substantial equivalence to a previously cleared device (K222930) by evaluating the impact of new ventilator compatibility labeling.
Here's an analysis based on the provided text, addressing the requested points where information is available or applicable:
1. A table of acceptance criteria and the reported device performance
The document does not provide a specific table of acceptance criteria and reported device performance in the context of an algorithmic diagnostic. Instead, it refers to the performance of the overall EVOLVE Nitric Oxide Delivery System, which is a hardware-based medical device.
The "Summary of Non-Clinical Tests" section mentions:
"The Mallinckrodt Ventilator / Gas Delivery System Validation Test Protocol was used to validate the hazards identified from risk input were mitigated. Testing was conducted across all platforms to demonstrate that the EVOLVE DS performs within published specifications. Ultimately, the requirements necessary for the operation of the EVOLVE Nitric Oxide Delivery System passed."
This indicates that the acceptance criteria were likely related to the device working within its published specifications when interfaced with the new ventilators, and the reported device performance was that it "passed" these requirements. However, specific quantitative metrics are not provided.
| Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|
| Device performs within published specifications when used with additional ventilator devices. | "Ultimately, the requirements necessary for the operation of the EVOLVE Nitric Oxide Delivery System passed." |
| Hazards identified from risk input are mitigated. | Validation testing confirmed mitigation. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
This information is not applicable and therefore not provided in the document. The study was a non-clinical validation test of device compatibility, not a clinical study on patient data.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This information is not applicable. The "ground truth" here would be the functional performance of the device and its compatibility with ventilators, established through engineering and technical validation rather than expert clinical consensus on diagnostic outcomes.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not applicable. Adjudication methods like 2+1 or 3+1 are typically used in clinical studies with human readers to resolve discrepancies in diagnoses or interpretations. This was a non-clinical validation.
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, an MRMC comparative effectiveness study was not done. The submission is not for an AI device or a diagnostic requiring human reader interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
No, a standalone algorithm performance study was not done. This device is a hardware delivery system, not an algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" used for this non-clinical validation was the functional performance of the device and its compatibility with the listed ventilators according to its published specifications and safety requirements. This would be established through engineering tests and measurements, rather than clinical ground truth types like pathology or expert consensus.
8. The sample size for the training set
This information is not applicable. There is no training set as it's not an AI/ML device.
9. How the ground truth for the training set was established
This information is not applicable, as there is no training set.
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Image /page/0/Picture/0 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 & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. Food & Drug Administration".
May 28, 2024
Malinckrodt Manufacturing LLC Jennifer Brett Senior Manager, Devices Global Regulatory Affairs 6603 Femrite Drive Madison, Wisconsin 53718
Re: K240410
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, MRQ Dated: April 29, 2024 Received: April 29, 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.
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 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.
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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,
Bradley Q. Quinn -S
Bradley Quinn Assistant Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthesia Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
Submission Number (if known)
Device Name
EVOLVE Nitric Oxide Delivery System
Indications for Use (Describe)
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 (NICU), and secondary targeted clinical setting is the transport of neonates.
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
In accordance with 21 CFR 807.92 the following summary of information is provided:
| Submitter Information | |
|---|---|
| Date: | 28 May, 2024 |
| 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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K22930 Predicate Device(s)
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.
The Evolve DS (delivery svstem) delivers INOMAX® Intended Use (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.
Technology The EVOLVE Nitric Oxide Delivery System utilizes 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 only changes to the device includes the labeling for compatibility with respiratory care device.
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 (K222930). All features are identical except those described in the table below.
| Feature /Specification | EVOLVE Nitric OxideDelivery SystemK222930 | 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 include:Coviden Puritan Bennet 840 Drager VN500 Getinge Flow-i/e/c Hamilton-C3 Hamilton-C6 Hamilton-G5 Hamilton-C1/T1 Vyaire LTV 1200 Smiths Medical BabyPac 100 |
Comparison to Predicate Device (original device)
Summary of Non-Clinical Tests
In the EVOLVE Nitric Oxide Delivery System 510(k) [K222930], the Ventilator / Gas Delivery System Validation Test Protocol was accepted, and the outcomes were used as justification on clearance of the submission.
The Mallinckrodt Ventilator / Gas Delivery System Validation Test Protocol was used to validate the hazards identified from risk input were mitigated. Testing was conducted across all platforms to demonstrate that the EVOLVE DS performs within published specifications.
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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.
§ 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.”