Acquiring fluorescent images for the visual assessment of circulation as a method for the evaluation of tissue perfusion and related tissue microcirculation in hands.

Device Description

The Xiralite fluorescence imaging system X4 detects fluorescence signals in the defined field of view using a highly sensitive camera for signal detection and light emitting diodes (LEDs) for excitation. Fluorescence signals typically result from illumination of a specific fluorophore, the fluorescence dye indocyanine green (ICG), which is administered intravenously. Fluorescence signals are recorded at different periodical time points, thus the resulting images display an image sequence. The frame rate is between half a second and a few seconds, typically one second. The duration of the entire image acquisition is dependent on the pharmacokinetics of the administered fluorophore, with ICG typically six minutes.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the Xiralite Fluorescence Imaging System X4. The information focuses on demonstrating substantial equivalence to a predicate device rather than presenting formal acceptance criteria and a detailed study proving the device meets those criteria.

Therefore, much of the requested information regarding specific acceptance criteria, detailed study design, sample sizes, and ground truth establishment is not explicitly available in the provided document.

However, based on the available information, here's a structured response.

Acceptance Criteria and Device Performance:

The document does not explicitly state quantitative acceptance criteria for the device's performance in terms of metrics like sensitivity, specificity, or accuracy. The basis for acceptance is demonstrating substantial equivalence to a predicate device, the Spy Fluorescent Imaging System (K042961, K073088). The "performance" described is largely functional and qualitative, focusing on its ability to acquire fluorescence images for visual assessment of circulation.

Criterion Type	Acceptance Criteria (Not explicitly stated quantitatively, inferred from SE)	Reported Device Performance (Inferred from SE and clinical use feedback)
Intended Use Equivalence	Function as a fluorescence imaging system for visual assessment of circulation for tissue perfusion/microcirculation.	"yes, the intended use is largely identical" to predicate.
Indications for Use (hands)	Acquire fluorescence images for visual assessment of circulation in hands.	"yes, the intended use is largely identical" to predicate.
Patient Population	Applicable to a general patient population.	"yes, a part of the patient population is identical" to predicate.
Accuracy of Imaging	Display distribution of injected contrast dye (ICG) in the vascular system over time.	"yes" - same method as predicate. Functionally equivalent.
Safety	Meet mechanical, electrical, thermal safety, EMC, and biocompatibility standards; no adverse events.	Non-clinical tests show safety. 10,000+ patient exams without reported adverse events.
Effectiveness/Functionality	Provide fluorescence images for visual assessment of circulation and tissue perfusion.	Users conclude "the device works as intended by safely providing fluorescence images."
Linearity of Signal	Show linear dependence of measured signal intensities with fluorophore concentration.	A test showed "linear dependence of the measured signal intensities... with the concentration of the fluorophore ICG."

Study Details:

The provided document describes the basis for substantial equivalence rather than a formal, standalone clinical study with predefined acceptance criteria for AI performance. The "study" mentioned is primarily a collection of non-clinical tests and user feedback from European clinical use.

Sample size used for the test set and the data provenance:
- Test set sample size: Not applicable in the context of a formal performance study with a 'test set' in the AI sense.
- Data provenance: The document references "more than 10,000 patient exams" from "more than 35 systems... in clinical use in hospitals as well as in physician offices, mainly in Germany" since 2009. This data is retrospective from real-world clinical use.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. The "ground truth" here is the real-world clinical observations by healthcare professionals using the device, whose qualifications are generally described as "Health care professionals." The document does not specify a panel of experts for ground truth establishment for a test set.
Adjudication method for the test set: Not applicable. There was no formal adjudication process for a specific test set. The conclusion of performance and safety is based on user feedback and the absence of reported adverse events.
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 MRMC or human-in-the-loop study with AI assistance was described. The device itself is an imaging system, not an AI-powered diagnostic algorithm.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: The device is an imaging system, not an algorithm, so a standalone algorithm-only performance study is not relevant in this context. The non-clinical tests showed the functional performance of the device itself (e.g., linearity of signal, safety standards).
The type of ground truth used:
- For safety and functional performance: Adherence to consensus standards (mechanical, electrical, thermal safety, EMC, biocompatibility) and linearity of signal with ICG concentration.
- For effectiveness/intended use: User feedback from clinical operation and the absence of reported adverse events over 10,000+ patient exams over several years.
The sample size for the training set: Not applicable. This is not an AI-driven device requiring a training set.
How the ground truth for the training set was established: Not applicable.

Summary

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mive

K130003

5 510(k) Summary

JAN 3 1 2014

[As Required by 21 CFR 807.92]

Manufacturer's Nameand Address:	mivenion GmbHRobert-Koch-Platz 410115 BerlinGermanyPhone: +49 30 6883792 0Fax: +49 30 6883792 99Mail: info@mivenion.com
Manufacturer ContactInformation:	Dr. Malte Bahnermivenion GmbHRobert-Koch-Platz 410115 BerlinGermanyPhone: +49 30 6883792 11Fax: +49 30 6883792 99Mail: bahner@mivenion.com
Date 510(k) SummaryPrepared:	2014 - 1 - 29
Proprietary Name:	Xiralite Fluorescence Imaging System X4
Common Name:	Fluorescence Angiographic System
Regulation Description:	Angiographic x-ray system
Regulation number:	21 CFR 892.1600
Product Code:	IZI OWN

· mivenion GmbH. Robert-Koch-Platz 4, 10115 Berlin, Germany

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Spy Fluorescent Imaging System (K042961, K073088), Legally Marketed Novadaq Technologies Inc. Predicate Devices: Device Description: The Xiralite fluorescence imaging system X4 detects fluorescence signals in the defined field of view using a highly sensitive camera for signal detection and light emitting diodes (LEDs) for excitation. Fluorescence signals typically result from illumination of a specific fluorophore, the fluorescence dye indocyanine green (ICG), which is administered intravenously. Fluorescence signals are recorded at different periodical time points, thus the resulting images display an image sequence. The frame rate is between half a second and a few seconds, typically one second. The duration of the entire image acquisition is dependent on the pharmacokinetics of the administered fluorophore, with ICG typically six minutes. Acquiring fluorescence images for the visual assessment Intended Use: of circulation as a method for the evaluation of tissue perfusion and related tissue microcirculation. Acquiring fluorescence images for the visual assessment Indications for Use: of circulation as a method for the evaluation of tissue perfusion and related tissue microcirculation in hands.

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Substantial Equivalence:
No.	Applicant DeviceXiralite Fluorescence Imaging System X4	Predicate DeviceSpy Fluorescent Imaging System	Equivalence to Spy FluorescentImaging System
2. Application
2.1	Intended Use	Acquiring fluorescent images for the visualassessment of circulation as an method forthe evaluation of tissue perfusion and relatedtissue microcirculation	Capturing and Viewing fluorescent images for thevisual assessment of blood flow as an adjunctivemethod for the evaluation of tissue perfusion, andflaps used in plastic-, micro- and reconstructivesurgical procedures;	yes, the intended use is largelyidentical
2.2	Indications forUse	Acquiring fluorescent images for the visualassessment of circulation as an method forthe evaluation of tissue perfusion and relatedtissue microcirculation in hands.	Capturing and Viewing fluorescent images for thevisual assessment of blood flow as an adjunctivemethod for the evaluation of tissue perfusion, andrelated tissue transfer circulation in tissue and freeflaps used in plastic-, micro- and reconstructivesurgical procedures; Intra-operative visualassessment of the coronary vasculature andbypass grafts during coronary artery bypass(CABG) surgery	yes, the intended use is largelyidentical
2.3	PatientPopulation	For use in all patients	Patients with vascular or reconstructive surgery	yes, a part of the patientpopulation is identical
2.4	Anatomicstructures	Vascular bed, including microcirculation(hands)	Vascular bed, including microcirculation (intra-operative)	yes
2.5	Environmentsof use	Hospital, outpatient clinic, specialist office	Hospital	yes, a part of the environments ofuse is identical

mivenion GmbH, Robert-Koch-Platz 4. 10115 Berlin. Germany

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K130003

No.		Applicant DeviceXiralite Fluorescence Imaging System X4	Predicate DeviceSpy Fluorescent Imaging System	Equivalence to Spy FluorescentImaging System
2.6	User group	Health care professionals	Health care professionals	yes
	5. Technology
5.1	Principle	Interaction of radiation source with contrast dye	Interaction of radiation source with contrast dye	yes
5.2	Method of...	displaying the distribution of an injected contrast dye in the vascular system, including microcirculation, over time	displaying the distribution of an injected contrast dye in the vascular system, including microcirculation, over time	yes
5.3	Detector	CCD camera	CCD camera	yes
5.4	Field of Viewsufficient forintended use	Yes, field of view of 1200cm2 (40cm x 30cm)sufficient for intended use	Yes, field of view of 56cm2 (7.5cm x 7.5cm)sufficient for intended use	yes
5.5	Penetrationdepthsufficient forintended use	Yes, penetration depth of light estimated to be 2 to 4cm in vivo, sufficient for intended use	Yes, penetration depth of light sufficient for intended use	yes
5.6	Contrast dyerequired	Yes (ICG)	Yes (ICG)	yes
5.7	Components	Radiation source, detector, signal processing	Radiation source, detector, signal processing	yes
5.8	Materials withpatientcontact	All materials with patient contact are biocompatible and can be disinfected	No patient contact	n/a

mivenion GmbH, Robert-Koch-Platz 4, 10115 Berlin, Germany

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Rationale for Substantial Equivalence: . . .

Nonclinical tests Testing in vitro testing:

Clinical tests In vivo testing: The comparison of the devices presented in the enclosed table demonstrates the substantial equivalence between the Xiralite fluorescence imaging system X4 and the predicate device. Like in most imaging procedures, the acquired images of the Xiralite fluorescence imaging system X4 as well as the images from the predicate device does not display a specific disease, but anatomical structures and their alteration by disease. The anatomical structure displayed by both devices is the vasculature, including the small vessels comprising the microcirculation. To enable this, both devices use the physical interaction of the output of a radiation source with a contrast dye injected into the vasculature. The generated radiation is focused on an anatomical region and displays the in vivo distribution of the contrast dye in the individual patient. All three devices are meant to be used solely by health care professionals.

Non-clinical tests of the Xiralite fluorescence imaging system X4, covering mechanical, electrical and thermal safety, electromagnetic compatibility and biocompatibility, performed in accredited laboratories, have shown that the device is safe. These tests are performed according to consensus standards, therefore providing information with regard to the predicate devices, which were also tested according to the same applicable standards. Therefore, these tests provide further evidence of substantial equivalence in addition to the features presented in the enclosed table.

Furthermore we performed a test to show a linear dependence of the measured signal intensities of fluorescence optical imaging with the Xiralite fluorescence imaging system X4 with the concentration of the fluorophore ICG. The shown linearity of the measured fluorescence signal intensity further supports substantial equivalence with the predicate device Philips Integris Systems, Release 2.

The Xiralite fluorescence imaging system X4 has a CE mark as a medical device for the European Union. Since 2009, more than 35 systems have been in clinical use in hospitals as well as in physician offices, mainly in Germany. On these systems, more than 10.000 patient exams have been performed without reported adverse events attributable to the Xiralite fluorescence

mivenion GmbH, Robert-Koch-Platz 4, 10115 Berlin, Germany

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imaging system X4.

The feedback from users concludes that the device works as intended by safely providing fluorescence images for the visual assessment of circulation as a method for the evaluation of tissue perfusion and related tissue microcirculation.

According to the available feedback from current clinical users in Europe and the lack of reported adverse events attributable to the Xiralite fluorescence imaging system X4 it can be concluded that the Xiralite fluorescence imaging system X4 is a safe medical device and performs as intended, namely by providing fluorescence images for the visual assessment of circulation as a method for the evaluation of tissue perfusion and related tissue microcirculation. Overall, it does not pose any new questions regarding safety or effectiveness conspared to the predicate device.

Conclusion:

As presented in the substantial equivalence comparison chart, the Xiralite fluorescence imaging system X4 and the predicate device have similar technological characteristics, and any minor differences do not raise different questions of safety or efficacy, as described in this submission. Furthermore, the Xiralite fluorescence imaging system X4 is at least as safe as the predicate device and performs as intended. This leads to the conclusion of substantial equivalence between the Xiralite fluorescence imaging system X4 and the predicate device.

mivenion GmbH, Robert-Koch-Platz 4, 10115 Berlin, Germany

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image contains the text "Public Health Service" in a bold, sans-serif font. The text is arranged vertically, with "Public Health" on the first line and "Service" on the second line. The text appears to be extracted from a document or sign.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

January 31, 2014

Mivenion GmbH Dr. Malte L. Bahner Managing Director Robert-Koch-Platz 4 Berlin, Germany, 10115

Re: K130003

Trade/Device Name: Xiralite Fluorescence Imaging System X4 Regulation Number: 21 CFR 892.1600 Regulation Name: Angiographic x-ray system Regulatory Class: Class II Product Code: IZI, OWN Dated: January 27, 2014 Received: January 30, 2014

Dear Dr. Bahner:

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. 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 (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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Page 2 - Dr. Malte L. Bahner

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

David Krause -S

for

Binita S. Ashar, M.D., M.B.A., F.A.C.S. Acting Director Division of Surgical Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.

510(k) Number (if known) K130003

Device Name

Xiralite Flourescence Imaging System X4

Indications for Use (Describe)

Acquiring fluorescent images for the visual assessment of circulation as a method for the evaluation of tissue perfusion and related tissue microcirculation in hands.

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)

. * 2 * ($ A 10)

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FORM FDA 3881 (1/14) For BSA

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Regulation Number and Section

§ 892.1600 Angiographic x-ray system.

(a)
Identification. An angiographic x-ray system is a device intended for radiologic visualization of the heart, blood vessels, or lymphatic system during or after injection of a contrast medium. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.