BLUE 400 is an accessory of the surgical microscope and allows the fluorescence observation of fluorophores with an excitation peak between 400 mm and the fluorescence emission observation comprising the spectrum in a spectral band of 620 - 710 nm.

The ZEISS BLUE 400 is a surgical microscope accessory used in fluorescent visualization of suspected grade III and IV gliomas during neurosurgery.

Device Description

The BLUE 400 is an accessory to the Zeiss surgical microscopes (OPMI PENTERO 800, OPMI PENTERO 900, and KINEVO 900), intended to allow intraoperative viewing of malignant glioma tissue under fluorescence. The BLUE 400 accessory is entirely composed of optical filters: the "Excitation" filter and the "Emission" filters. The Excitation filter is designed to filter all light wavelengths except 400 - 470 nanometers and is optimized to pass light between 400 - 410 nanometers. The Emission filters are designed to filter all light wavelengths except 430 - 800 nanometers and is optimized to pass light between 620 - 710 nanometers.

When installed in the surgical microscopes (class I), the BLUE 400 introduces optical filters to the illumination and viewing optical paths. The BLUE 400 includes installation of a software license that facilitates use of the accessory. After the SW license is installed, the user has the option to switch from the normal white light mode of the surgical microscope to the BLUE 400 mode.

The BLUE 400 accessory, when installed in the surgical microscopes, is intended to be used in conjunction with an approved optical imaging agent that is excited mainly in the wavelength range of 400 – 410 nanometers and fluoresces in the wavelength range of 620 - 710 nanometers.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the BLUE 400 device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated in a quantitative manner (e.g., specific thresholds for irradiance or power). Instead, they are implied by the "Passed" result for each test, indicating that the device met the defined specifications for each performance parameter. The study is a bench performance test comparing the subject device (BLUE 400) to a predicate device (Leica FL400).

Test	Acceptance Criteria (Implied)	Reported Device Performance
Spectrum of the Illumination Source	Irradiance spectrum (250 nm - 1020 nm, mW/cm²) verified and assessed prior to excitation filter application.	Passed
Maximum Power and Irradiance of the Illumination Source	Maximum output power and irradiance measured and verified prior to excitation filter application.	Passed
Irradiance Spectrum of the Excitation Light and Spectral Response of the Excitation Filter	Irradiance spectrum (250 nm - 1020 nm) of illumination light after excitation filter passage measured; 50% decrease edges of blue excitation peak calculated.	Passed
Maximum Excitation Power and Power Density	Maximum power (mW) and power density (mW/cm²) of excitation light measured at various working distances and zoom settings and compared to the predicate device.	Passed
Optical Path Loss	Optical path loss calculated by dividing output signal (eyepiece without emission filter) by illumination signal (focal plane with spectrometer).	Passed
Spectrum of the Emission Filter	Spectrum (350 nm - 1050 nm) of the emission filter (integrated into microscope) measured; 50% edge of the spectrum calculated.	Passed
Homogeneity of the Excitation Light at the Focal Point	Intensity profile of reflected signal from white paper imaged by camera demonstrated homogeneity.	Passed
System Sensitivity	Fluorescence signal in the eyepiece of the subject device compared to the predicate device using a fluorescent target.	Passed
Pre-Operative Phantom Test	Suitability of the ZEISS BLUE 400 test phantom for pre-operative checks of KINEVO 900 and OPMI PENTERO 900 demonstrated via camera imaging and eyepiece observation.	Passed
Spectrum of Camera Filter	Spectrum at camera interface measured to demonstrate camera filter blocks near infrared and infrared leakage of excitation light.	Passed

2. Sample Size Used for the Test Set and Data Provenance

The document describes bench performance testing. Therefore, the "test set" in the traditional sense of patient data is not applicable. The testing involves:

Test Sets: The devices themselves (subject device BLUE 400 and predicate device Leica FL400) and various optical components (filters, light sources, specialized targets/phantoms).
Data Provenance: The tests were conducted internally by Carl Zeiss Meditec AG, as part of their 510(k) submission. This is a prospective bench study. No external data sources or patient data are mentioned.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Not applicable. This was a bench performance study assessing physical and optical properties, not a clinical study requiring expert interpretation of patient data to establish ground truth. The "ground truth" was established by the physical measurements and calculations against defined specifications.

4. Adjudication Method for the Test Set

Not applicable. This was a direct measurement and comparison bench study, not a clinical study requiring adjudication of expert readings.

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

Not applicable. This device is an accessory (an optical filter) to a surgical microscope, not an AI or imaging diagnostic tool that would typically involve a multi-reader multi-case study for diagnostic accuracy or human performance improvement.

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

The device itself is an optical filter system for a surgical microscope. It does not have an "algorithm" in the sense of an AI or software that performs standalone interpretation. Its function is to modify light for improved visualization by a human surgeon. Therefore, standalone algorithm performance is not applicable. The document does mention Software verification testing was performed in accordance with FDA Guidance to demonstrate the software (for the license installation and mode switching) is performing as intended. This is analogous to a standalone performance check for the software component, but not for an interpretative algorithm.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

For the bench performance tests, the "ground truth" was established by:

Physical measurements: Using calibrated instruments like spectrometers, power meters, and thermopiles to measure optical properties (irradiance spectrum, power, density, emission spectrum).
Calculations: Such as calculating the 50% decrease edges of spectral peaks and optical path loss.
Comparison to predefined specifications: The results were evaluated against specific technical requirements and specifications for each test.
Comparison to a predicate device: For certain tests like maximum excitation power density and system sensitivity, the performance of the subject device was compared directly to the predicate device (Leica FL400).

8. The Sample Size for the Training Set

Not applicable. This is not a machine learning or AI-based device that requires a "training set."

9. How the Ground Truth for the Training Set Was Established

Not applicable. As above, there is no training set for this device.

Summary

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July 22, 2022

Carl Zeiss Meditec AG % Maria Golovina Head of Regulatory Affairs - USA 5300 Central Parkway Dublin, California 94568

Re: K211346

Trade/Device Name: BLUE 400 Regulation Number: 21 CFR 882.4950 Regulation Name: Diagnostic Neurosurgical Microscope Filter Regulatory Class: Class II Product Code: QFX Dated: June 16, 2022 Received: June 21, 2022

Dear Maria Golovina:

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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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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 (QS) 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 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,

Adam D. Pierce, Ph.D. Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine 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) K211346

Device Name BLUE 400

Indications for Use (Describe)

The ZEISS BLUE 400 is a surgical microscope accessory used in fluorescent visualization of suspected grade III and IV gliomas during neurosurgery.

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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In accordance with 21 CFR 807.92 the 510(k) Summary for the BLUE 400 is provided below.

SUBMITTER 1.

Applicant:	Carl Zeiss Meditec AGGoeschwizer Strasse 51-52D-07745 JenaGermany
Primary Correspondent	Maria GolovinaHead of Regulatory Affairs - USACarl Zeiss Meditec, Inc.5300 Central Parkway Dublin, CA 94568(925) 216-1078 Phone (925) 557-4259 FaxE-mail: maria.golovina@zeiss.com (preferred)
Secondary Correspondent	Chaitali GawdeSenior Regulatory Affairs SpecialistCarl Zeiss Meditec, Inc.5300 Central Parkway Dublin, CA 94568(925) 557-4202 PhoneE-mail: chaitali.gawde@zeiss.com
Date Prepared:	July 22, 2022

DEVICE 2.

Device Trade Name: BLUE 400 Classification: 21 CFR 882.4950 Diagnostic Neurosurgical Microscope Filter Regulatory Class: II Product Code: QFX

PREDICATE DEVICE 3.

Predicate Device: Leica FL400 (DEN180024) Classification: 21 CFR 882.4950 Diagnostic Neurosurgical Microscope Filter Regulatory Class: II Product Code: QFX

DEVICE DESCRIPTION 4.

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510(k) Summary

INDICATIONS FOR USE ર.

The ZEISS BLUE 400 is a surgical microscope accessory used in fluorescent visualization of suspected grade III and IV gliomas during neurosurgery.

SUBSTANTIAL EQUIVALENCE 6.

Attribute	Subject DeviceBLUE 400K211346	Predicate DeviceLeica FL400DEN180024	Equivalency Analysis
Indications for use	BLUE 400 is an accessory ofthe surgical microscope andallows the fluorescenceobservation of fluorophoreswith an excitation peakbetween 400 nm and 410 nmand the fluorescence emissionobservation comprising thespectrum in a spectral band of620 - 710 nm.	The Leica FL400 is a surgical microscope accessory filter setfor viewing fluorescence offluorophores comprising anexcitation filter for bluespectral range 380 nm – 430nm and an observation filtercomprising the long-waveblue, green, yellow and redspectrum in the spectral bandgreater than 444 nm.	Similar
	The ZEISS BLUE 400 is asurgical microscope accessoryused in fluorescentvisualization of suspectedgrade III and IV gliomasduring neurosurgery.	The FL400 is a surgicalmicroscope accessory used influorescent visualization ofsuspected grade III or IVgliomas during neurosurgery.
Intended Use	Patients undergoingneurological procedures.	Patients undergoingneurological procedures.	Identical
Type of Component	Accessory to themicroscope (Filter)	Accessory to the microscope(Filter)	Identical

Table 1. Subject to Predicate Device Comparison Table - Indications for Use

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Attribute	Subject DeviceK211346	Predicate DeviceDEN180024	EquivalencyAnalysis
Device name	BLUE 400	Leica FL400	Different
Manufacturer	Carl Zeiss Meditec AGGoeschwitzer Strasse 51-52D-07745 Jena, Germany	Leica Microsystems(Schweiz) AG	Different
Classification ProductCode	QFX	QFX	Identical
Regulation #	21 CFR 882.4950 (Diagnosticneurosurgical microscopefilter)	21 CFR 882.4950(Diagnostic neurosurgicalmicroscope filter)	Identical
FluorescenceExcitation SpectralWindow	400 nm - 430 nm	380 – 430 nm	Equivalent forfluorescence agent
Spectrum of theEmission Filter	430 - 800 nm	300 – 1100 nm	Equivalent fordetecting thefluorescence agent
Combination Device	No	No	Identical
Visualization Result	Fluorescent image ofdistribution of theaccumulated protoporphyrinIX (PpIX) in malignant tissueduring operation.	Fluorescent image ofdistribution of theaccumulated protoporphyrinIX (PpIX) in malignant tissueduring operation.	Identical
Visualization of Real-Time Images	Yes	Yes	Identical
Visualization onInterface/Display	Yes	Yes	Identical
Light Specifications –Type	White Light - Fluorescence	White Light – Fluorescence	Identical

Table 2. Subject to Predicate Device Comparison Table - Technical Characteristics

7. SUMMARY OF STUDIES

Sterilization and Shelf Life

The device is provided non-sterile. Cleaning instructions are provided in the user users to follow the cleaning procedures of the surgical operating microscope that the BLUE 400 is installed in. Shelf-Life is not applicable.

Biocompatibility

The device does not have patient-contacting materials; therefore, a biocompatibility assessment is not needed for this device.

Performance Testing - Bench

In order for BLUE 400 filter to work, it has to be installed onto a surgical microscope and a software license to the microscope has to be installed. Software verification testing was performed in accordance with FDA Guidance "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" to demonstrate that software is performing as intended.

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510(k) Summary

Non-clinical system testing provided an evaluation of the performance of the system relevant to each of the system specifications. The functional and system level testing showed that the defined specifications.

The testing was completed for the predicate and subject device and the performance of the subject device was compared to the predicate.

Finally, special controls testing has also been performed and met the defined specifications. The following special controls testing has been conducted with and without cover glass.

Test	Test Method Summary	Results
Spectrum of theIllumination Source	The irradiance spectrum (250 nm - 1020 nm,mW/cm^2) of the illumination source wasmeasured and verified with a spectrometer. Thesemeasurements were assessed prior to application ofthe excitation filter module.	Passed
Maximum Power andIrradiance of theIllumination Source	The maximum output power and irradiance ofillumination sources were measured and verifiedwith a power meter at the end of the microscopelight guide. These measurements were assessedprior to application of the excitation filter module.	Passed
Irradiance Spectrum ofthe Excitation Light andSpectral Response of theExcitation Filter	The irradiance spectrum (250 nm - 1020 nm) of theillumination light, following passage through theexcitation filter module, was measured at a workingdistance of 30 cm with a spectrometer. The edges at50% decrease of the blue excitation peak werecalculated respectively.	Passed
Maximum ExcitationPower and PowerDensity	The maximum power (mW) and power density(mW/cm^2) of the excitation light was measuredwith a thermopile, at multiple different workingdistances (22.5 - 30 cm) and zoom settings,including the maximum and minimum zoom.The power density measurements of the subjectdevice were compared to the predicate device.	Passed
Optical Path Loss	To determine the overall detectable light output andthe total losses in relation to device workingdistance and zoom setting, optical path loss wascalculated by dividing the output signal measured atthe microscope eyepiece (without emission filter)by the illumination signal measured with aspectrometer at the microscope focal plane for thesame zoom setting. A reflection standard (whitesilicon remission disc) was used at a workingdistance of 35 cm.	Passed
Spectrum of theEmission Filter	The spectrum (350 nm - 1050 nm) of the emissionfilter when integrated in the surgical operating	Passed
510(k) Summary &text-align: left;">K211346 Page 7 of 7
Test	Test Method Summary	Results
	microscope was measured with a spectroradiometerto include all the coating and optics that affects thespectrum of the observation path. For this test theexcitation filter was removed, and a reflectionstandard was used at the device focal plane withdifferent zoom settings. To compare the light thatpasses the observation optics and emission filter,the 50% edge of the spectrum was calculated.	Passed
Homogeneity of theExcitation Light at theFocal Point	The reflected signal from a white sheet of paperpositioned at 30 cm working distance was imagedby the surgical operating microscope camera andthe intensity profile was calculated to demonstratethe homogeneity of the excitation light.	Passed
System Sensitivity	As a diffusely reflecting and fluorescent disc theZEISS BLUE 400 fluorescent target was used andpositioned at a microscope working distance of 22.5cm. The zoom setting was chosen to lead to thesame image size of the target for all three devices.	Passed
	The fluorescence signal in the eyepiece of thesubject device was compared to the predicatedevice.
Pre-Operative PhantomTest	This test was conducted to demonstrate that theZEISS BLUE 400 test phantom is suitable for thepre-operative checks of the KINEVO 900 andOPMI PENTERO 900. The phantom has onefluorescent area and was imaged by the surgicalmicroscope camera. The same test was repeated byobservation through the microscope eyepiece.	Passed
Spectrum of CameraFilter	The spectrum at the camera interface was measuredwith a spectroradiometer to demonstrate thatcamera filter can block near infrared and infraredleakage of excitation light to the camera.	Passed

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510(k) Summary

BLUE 400 has not been evaluated to support the use of the device in a pediatric patient population.

CONCLUSION 8.

The indications for use of the subject device, BLUE 400, are equivalent to the indications for use of the predicate device, Leica FL400. The technological characteristics and risk profile of the subject device are similar to the predicate device. Based on the similarities of the indications for use, technological characteristics, and the results of the non-clinical performance testing, the BLUE 400 filter is substantially equivalent to the legally marked predicate device, Leica FL400.

Regulation Number and Section

§ 882.4950 Diagnostic neurosurgical microscope filter.

(a)
Identification. A diagnostic neurosurgical microscope filter is a device intended for use during neurosurgery to visualize fluorescence and enhance visualization of tissue associated with a specific disease or condition.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use, and verify and validate filter specifications and functional characteristics, including the following:
(i) Spectrum and intensity of the illumination source;
(ii) Spectrum of the excitation and emission filter modules when integrated in the surgical operating microscope;
(iii) Excitation power and power density;
(iv) Optical path loss from illumination source to objective lens or microscope camera;
(v) Homogeneity of the excitation light at the focal plane;
(vi) Fluorescence detection sensitivity;
(vii) Verification of calibration or preoperative procedures; and
(viii) If camera-based, spectral sensitivity of the camera.
(2) Labeling must include:
(i) Identification of the filter characteristics in conjunction with a compatible surgical operating microscope, to include the following:
(A) Illumination spectrum and power density; and
(B) Excitation and emission filter spectra.
(ii) Instructions for calibration or preoperative checks to ensure device functionality prior to each use;
(iii) Instructions for use with compatible surgical operating microscopes, external light sources, and cameras;
(iv) A warning that the device should only be used with fluorophores approved for use within the specified spectral ranges; and
(v) A warning that the device is not a standalone diagnostic.