The Nautilus VF ECMO Oxygenator with integrated heat exchanger is intended to provide assisted long-term extracorporeal circulation and physiologic gas exchange (oxygenation and carbon dioxide removal) of the patient's blood for up to 48 hours in adult and pediatric adolescent patients with acute respiratory failure or acute cardiopulmonary failure, where other available treatment options have failed, and continued clinical deterioration is expected or the risk of death is imminent. The integrated heat exchanger is intended to heat or cool the blood as needed during use. Integrated fluid path pressure, temperature, and oxygen saturation monitoring is achieved by built-in sensor modules.

Device Description

The Nautilus™ ECMO oxygenators are diffusion membrane oxygenators used in extracorporeal life support procedures to oxygenate blood, remove carbon dioxide and regulate blood temperature. Blood enters the device and passes through both the heat exchange membrane, where temperature is adjusted, and the gas transfer membrane, where oxygen is added and carbon dioxide is removed.

The Nautilus™ VF ECMO Oxygenator device contains integrated sensors that connects to the VitalFlow Console (K230364) for the display of measured parameters. The following measured parameters are measured: inlet pressure, inlet oxygen saturation, outlet oxygen saturation, and outlet blood temperature. The difference between the inlet and outlet pressure, is calculated. The device is intended to be interconnected with a VitalFlow Console device that receives digital data from the oxygenator.

The oxygenator devices are single-use, nontoxic, non-pyrogenic, and not made from natural latex rubber materials.

AI/ML Overview

The provided FDA 510(k) summary for the Nautilus VF ECMO Oxygenator describes the device and its substantial equivalence to a predicate device. However, it does not contain information typically found in a study proving a device meets acceptance criteria within the context of AI/ML-powered medical devices.

This document is for a medical device (an oxygenator) and its associated monitoring components, not an AI/ML diagnostic or prognostic algorithm. Therefore, the questions related to AI/ML specific criteria (such as effect size of human readers with AI vs. without AI, ground truth establishment for training sets, number of experts for ground truth, etc.) are not applicable in this context.

Here's an analysis of the information that is present or can be inferred, formatted to address your questions where possible, and noting where information is missing or irrelevant to this type of device:

Device Acceptance Criteria and Performance

The document describes "Performance Evaluations" and "Special Controls" that were met to demonstrate substantial equivalence to the predicate device (Nautilus™ Smart ECMO Module (K191935) and Nautilus™ ECMO Oxygenator (K191935)). These act as the acceptance criteria for the device clearance.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria/Evaluation	Reported Device Performance
Performance Evaluations	Electrical Safety/EMC	Evaluated, demonstrated substantial equivalence.
	Software Validation	Evaluated, demonstrated substantial equivalence.
	Cybersecurity analysis	Evaluated, demonstrated substantial equivalence.
Special Controls	Technological Characteristics	Geometry and design parameters are consistent with intended use. Compatible with other ECLS devices. Oxygenator geometry is same as predicate. Electronic module modified but demonstrated equivalent performance.
	Biocompatibility	Demonstrated biocompatible for prolonged use per ISO 10993-1:2009 and GLP (21 CFR 58). No modifications to blood contact surfaces.
	Sterility and Shelf-life	Testing demonstrates sterility as provided, and maintenance of sterility, integrity, durability, and reliability over stated shelf-life.
	Non-clinical Performance	Substantial equivalence demonstrated by bench performance, mechanical integrity, electromagnetic compatibility, software, durability, reliability, and accuracy. Further demonstrated by EMC, software validation, and cybersecurity analysis.
	In vivo Evaluation	Demonstrates performance over long-term duration in a biologic test system. Summary of initial real-world clinical experience into ELSO registry was included. Original design's evaluation applicable as oxygenator design is unchanged.
	Labeling	Includes detailed summary of non-clinical evaluations, installation, setup, maintenance, changeout, adverse effects, and performance characteristics related to compatibility.

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

The document mentions "bench studies" for performance evaluations, and "in vivo evaluation" using a "biologic test system" and a "summary... described the initial real-world clinical experience... into the ELSO registry."

Sample Size for Bench Studies: Not specified. Bench studies typically involve a set number of device units for various tests (e.g., electrical, mechanical, software).
Sample Size for In Vivo Evaluation: Not specified, but refers to a "biologic test system" and "initial real-world clinical experience with the first records of clinical ECMO cases entered sequentially into the ELSO registry." The exact number of cases or subjects is not provided in this summary.
Data Provenance: The "ELSO registry" implies multi-center, international data, but the specific country of origin or whether it's retrospective/prospective is not detailed for the "real-world clinical experience" summary. The "biologic test system" would be a controlled lab setting.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not applicable and not provided for this type of medical device. The evaluation of an oxygenator focuses on its physical, chemical, electrical, and biological performance characteristics, not on diagnostic accuracy requiring expert interpretation or "ground truth" establishment in the way an AI algorithm for image analysis would.

4. Adjudication method for the test set

This information is not applicable and not provided. Adjudication methods (like 2+1, 3+1) are typically used for establishing ground truth in clinical studies involving interpretation (e.g., by radiologists) where there might be disagreements, which is not the case for an oxygenator's performance evaluation.

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 as this is not an AI/ML-driven diagnostic or assistive device requiring human reader interaction.

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

This information is not applicable as this is not an AI/ML-driven device. The device has integrated sensors and connects to a console for display, so there's a human-in-the-loop for monitoring parameters, but it's not an AI algorithm.

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

For an oxygenator, "ground truth" would refer to established scientific and engineering principles, validated measurement techniques, and regulatory standards. For example:

Biocompatibility: Established by adherence to ISO 10993 standards.
Sterility: Validated sterilization methods and testing.
Performance (e.g., gas exchange, heat exchange): Measured against validated laboratory methods and established clinical ranges for physiological parameters (e.g., blood oxygenation, CO2 removal).
Safety (Electrical/EMC): Adherence to relevant IEC standards.
In vivo: Performance in a "biologic test system" and "real-world clinical experience" as mentioned, assessed against physiological outcomes.

8. The sample size for the training set

This information is not applicable as this is not an AI/ML-driven device with a "training set" in the machine learning sense. The device is hardware with integrated sensors and software components that are validated, not trained.

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

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

Summary

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October 4, 2023

Michigan Critical Care Consultants, Inc. (d.b.a MC3 Inc.) Martha Rumford VP Regulatory 2555 Bishop Circle West Dexter, Michigan 48130

Re: K232767

Trade/Device Name: Nautilus VF ECMO Oxygenator Regulation Number: 21 CFR 870.4100 Regulation Name: Extracorporeal Circuit And Accessories For Long-Term Respiratory/Cardiopulmonary Failure Regulatory Class: Class II Product Code: BYS Dated: September 7, 2023 Received: September 11, 2023

Dear Martha Rumford:

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.

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).

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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 OS 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 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-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,

Nicole M. Gillette -S

Nicole Gillette Assistant Director DHT2B: Division of Circulatory Support, Structural and Vascular Devices OHT2: Office of Cardiovascular Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

Submission Number (if known)

K232767

Device Name

Nautilus VF ECMO Oxygenator

Indications for Use (Describe)

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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Image /page/3/Picture/0 description: The image shows the logo for MC3 Cardiopulmonary. The logo consists of a red abstract symbol on the left, followed by the text "MC3" in large, bold, dark blue letters. Below "MC3" is the word "Cardiopulmonary" in a smaller, lighter blue font. The red symbol appears to be composed of three curved shapes arranged in a circular pattern.

510(k) Summary

Sponsor Information:
Owner/Applicant/Submitter:	Michigan Critical Care Consultants, Inc.(d.b.a. MC3 Inc.)2555 Bishop Circle WestDexter, MI 481301-734-995-9089Registration number: 3011468686
Contact Person:	Martha Rumford
Date Prepared:	Sept 5, 2023
Device Names/Classification:
Device Trade Name:	Nautilus™ VF ECMO Oxygenator
Device Common Name:	Oxygenator, Long Term Support Greater Than 6 hours
Regulation Name:	Extracorporeal circuit and accessories for long-termrespiratory/cardiopulmonary failure
Regulation Number:	21 CFR 870.4100
Product Code:	BYS
Predicate:	Nautilus™ Smart ECMO Module (K191935)Nautilus™ ECMO Oxygenator (K191935)

Indications for Use:

The Nautilus™ VF ECMO Oxygenator with integrated heat exchanger is intended to provide assisted extracorporeal circulation and physiologic gas exchange of the patient's blood for up to 48 hours in adult and pediatric adolescent patients with acute respiratory failure or acute cardiopulmonary failure, where other available treatment options have failed, and continued clinical deterioration is expected or the risk of death is imminent. The integrated heat exchanger is intended to heat or cool the blood as needed during use. Integrated fluid path pressure, temperature, and oxygen saturation monitoring achieved by built-in sensors.

Device Description:

The Nautilus™ VF ECMO Oxygenator device contains integrated sensors that connects to the VitalFlow Console (K230364) for the display of measured parameters. The following measured parameters are

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Image /page/4/Picture/0 description: The image shows the logo for MC3 Cardiopulmonary. The logo consists of a red abstract symbol on the left, followed by the text "MC3" in large, bold, dark blue letters. Below "MC3" is the word "Cardiopulmonary" in a smaller, lighter font, also in dark blue. The red symbol appears to be composed of three curved shapes arranged in a circular pattern.

measured: inlet pressure, inlet oxygen saturation, outlet oxygen saturation, and outlet blood temperature. The difference between the inlet and outlet pressure, is calculated. The device is intended to be interconnected with a VitalFlow Console device that receives digital data from the oxygenator.

The oxygenator devices are single-use, nontoxic, non-pyrogenic, and not made from natural latex rubber materials.

Performance Evaluations:

Evaluation and testing were executed to demonstrate the substantial equivalence of the subject devices. Performance assessments for substantial equivalence were accomplished through bench studies that included the following evaluations:

Electrical Safety/EMC ●
Software Validation ●
Cyber security analysis

Substantial Equivalence:

Substantial equivalence analysis includes comparison to the Nautilus™ Smart ECMO Module (Predicate).

Special Controls met for the Nautilus™ oxygenators are:

. Technological Characteristics: Geometry and design parameters are consistent with the device's intended use in extracorporeal life support procedures. The subject device is designed to be compatible with other extracorporeal circuit devices and accessories. Geometry and design parameters of the oxygenator are the same for the Nautilus Smart and Nautilus VF oxygenators. The electronic module of the Nautilus Smart (hardware and software) included for monitoring the circuit parameters have been modified for the Nautilus VF Oxygenator and demonstrated to perform equivalently.
. Biocompatibility: The subject device is demonstrated to be biocompatible for prolonged use in circulating blood in accordance with ISO 10993-1:2009 and in accordance with GLP (21 CFR 58). There were no modifications to the blood contact surfaces or design.
. Sterility and Shelf-life: Testing demonstrates the sterility of the subject device as provided and that it maintains its sterility, integrity, durability, and reliability over the stated shelf-life of the device.
. Non-clinical Performance: Substantial equivalence is demonstrated by performance characteristics on the bench, mechanical integrity, electromagnetic compatibility, software, durability, reliability, and accuracy. Substantial equivalence is demonstrated by performance characteristics of electromagnetic compatibility and software validation, as well as an additional analysis for cybersecuity.
. In vivo Evaluation: In vivo evaluation demonstrates the subject device's performance over a long-term duration of use in a biologic test system. In addition to in-vivo study, a summary was prepared that described the initial real-world clinical experience of the device with the first records of clinical ECMO cases entered sequentially into the ELSO registry. This in vivo

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Image /page/5/Picture/0 description: The image contains the logo for MC3 Cardiopulmonary. The logo consists of a red abstract symbol on the left, followed by the text "MC3" in large, bold, dark blue letters. Below "MC3" is the word "Cardiopulmonary" in a smaller, lighter font, also in dark blue. The red symbol appears to be composed of three curved shapes arranged in a circular pattern.

evaluation of the original design remains applicable to the Nautilus VF Oxygenator because the oxygenator design is unchanged while the non-patient contacting components were modified.

Labeling: The Instructions for Use includes a detailed summary of the non-clinical evaluations pertinent to the device's use in an extracorporeal circuit. Adequate instructions are included with respect to installation, circuit setup, maintenance during a procedure, changeout, adverse effects, and performance characteristics relevant to compatibility among different devices and accessories in the circuit.

Conclusion:

The Nautilus™ VF ECMO Oxygenators are substantially equivalent to the Predicate device with respect to intended use, design, materials of construction, principles of operation, performance and specifications. The risks of this device are mitigated by meeting the Special Controls required by the regulation, 21 CFR 870.4100.

Regulation Number and Section

§ 870.4100 Extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure.

(a)
Identification. An extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary support (>6 hours) is a system of devices and accessories that provides assisted extracorporeal circulation and physiologic gas exchange of the patient's blood in patients with acute respiratory failure or acute cardiopulmonary failure, where other available treatment options have failed, and continued clinical deterioration is expected or the risk of death is imminent. The main devices and accessories of the system include, but are not limited to, the console (hardware), software, and disposables, including, but not limited to, an oxygenator, blood pump, heat exchanger, cannulae, tubing, filters, and other accessories (e.g., monitors, detectors, sensors, connectors).(b)
Classification —Class II (special controls). The special controls for this device are:(1) The technological characteristics of the device must ensure that the geometry and design parameters are consistent with the intended use, and that the devices and accessories in the circuit are compatible;
(2) The devices and accessories in the circuit must be demonstrated to be biocompatible;
(3) Sterility and shelf-life testing must demonstrate the sterility of any patient-contacting devices and accessories in the circuit and the shelf life of these devices and accessories;
(4) Non-clinical performance evaluation of the devices and accessories in the circuit must demonstrate substantial equivalence of the performance characteristics on the bench, mechanical integrity, electromagnetic compatibility (where applicable), software, durability, and reliability;
(5) In vivo evaluation of the devices and accessories in the circuit must demonstrate their performance over the intended duration of use, including a detailed summary of the clinical evaluation pertinent to the use of the devices and accessories to demonstrate their effectiveness if a specific indication (patient population and/or condition) is identified; and
(6) Labeling must include a detailed summary of the non-clinical and in vivo evaluations pertinent to use of the devices and accessories in the circuit and adequate instructions with respect to anticoagulation, circuit setup, performance characteristics with respect to compatibility among different devices and accessories in the circuit, and maintenance during a procedure.