BLUE 400
Device Facts
| Record ID | K211346 |
|---|---|
| Device Name | BLUE 400 |
| Applicant | Carl Zeiss Meditec, AG |
| Product Code | QFX · Neurology |
| Decision Date | Jul 22, 2022 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 882.4950 |
| Device Class | Class 2 |
Indications for Use
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 Story
BLUE 400 is a surgical microscope accessory (optical filter set) for Zeiss OPMI PENTERO 800/900 and KINEVO 900 microscopes; enables intraoperative fluorescence visualization of malignant glioma tissue. Input: white light illumination; device transforms light via excitation filter (400-470 nm, optimized 400-410 nm) and emission filter (430-800 nm, optimized 620-710 nm). Output: fluorescent image of protoporphyrin IX (PpIX) distribution in tissue. Used in neurosurgery by surgeons; requires software license installation on microscope to enable 'BLUE 400 mode' switching. Provides real-time visualization via eyepiece or camera interface; assists surgeons in identifying malignant tissue boundaries during resection, potentially improving tumor removal outcomes.
Clinical Evidence
No clinical data. Bench testing only. Performance verified via spectral measurements of illumination/excitation/emission filters, power density, optical path loss, homogeneity, and system sensitivity compared to predicate. Software verification performed per FDA guidance.
Technological Characteristics
Optical filter accessory set (Excitation and Emission filters). Integrates into Zeiss surgical microscopes (OPMI PENTERO 800/900, KINEVO 900). Requires software license for operation. Non-sterile. No patient-contacting materials. Spectral range: Excitation 400-470 nm (optimized 400-410 nm); Emission 430-800 nm (optimized 620-710 nm).
Indications for Use
Indicated for fluorescent visualization of suspected grade III and IV gliomas during neurosurgery in adult patients. Not evaluated for pediatric populations.
Regulatory Classification
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.
Special Controls
In combination with the general controls of the FD&C Act, the diagnostic neurosurgical microscope filter is subject to the following special controls: - (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; - Spectrum of the excitation and emission filter modules when integrated in the (ii) 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 pre-operative procedures; and - (viii)If camera-based, spectral sensitivity of the camera. - (2) Labeling must include: - Identification of the filter characteristics in conjunction with a compatible surgical (i) operating microscope, to include the following: - (A) Illumination spectrum and power density; and - (B) Excitation and emission filter spectra. - (ii) Instructions for calibration or pre-operative 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 - A warning that the device is not a standalone diagnostic. (v)
*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.
Predicate Devices
- Leica FL400 (DEN180024)
Submission Summary (Full Text)
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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)
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.
| Type of Use (Select one or both, as applicable) | |
|--------------------------------------------------------------------------------------|-----------------------------------------------|
| <span style="font-size: 10pt;">☑</span> 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 AG<br>Goeschwizer Strasse 51-52<br>D-07745 Jena<br>Germany |
|-------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Primary Correspondent | Maria Golovina<br>Head of Regulatory Affairs - USA<br>Carl Zeiss Meditec, Inc.<br>5300 Central Parkway Dublin, CA 94568<br>(925) 216-1078 Phone (925) 557-4259 Fax<br>E-mail: maria.golovina@zeiss.com (preferred) |
| Secondary Correspondent | Chaitali Gawde<br>Senior Regulatory Affairs Specialist<br>Carl Zeiss Meditec, Inc.<br>5300 Central Parkway Dublin, CA 94568<br>(925) 557-4202 Phone<br>E-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.
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.
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# 510(k) Summary
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.
#### INDICATIONS FOR USE ર.
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.
#### SUBSTANTIAL EQUIVALENCE 6.
| Attribute | Subject Device<br>BLUE 400<br>K211346 | Predicate Device<br>Leica FL400<br>DEN180024 | Equivalency Analysis |
|---------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------|
| Indications for use | BLUE 400 is an accessory of<br>the surgical microscope and<br>allows the fluorescence<br>observation of fluorophores<br>with an excitation peak<br>between 400 nm and 410 nm<br>and the fluorescence emission<br>observation comprising the<br>spectrum in a spectral band of<br>620 - 710 nm. | The Leica FL400 is a surgical microscope accessory filter set<br>for viewing fluorescence of<br>fluorophores comprising an<br>excitation filter for blue<br>spectral range 380 nm – 430<br>nm and an observation filter<br>comprising the long-wave<br>blue, green, yellow and red<br>spectrum in the spectral band<br>greater than 444 nm. | Similar |
| | The ZEISS BLUE 400 is a<br>surgical microscope accessory<br>used in fluorescent<br>visualization of suspected<br>grade III and IV gliomas<br>during neurosurgery. | The FL400 is a surgical<br>microscope accessory used in<br>fluorescent visualization of<br>suspected grade III or IV<br>gliomas during neurosurgery. | |
| Intended Use | Patients undergoing<br>neurological procedures. | Patients undergoing<br>neurological procedures. | Identical |
| Type of Component | Accessory to the<br>microscope (Filter) | Accessory to the microscope<br>(Filter) | Identical |
Table 1. Subject to Predicate Device Comparison Table - Indications for Use
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| Attribute | Subject Device<br>K211346 | Predicate Device<br>DEN180024 | Equivalency<br>Analysis |
|-----------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------|
| Device name | BLUE 400 | Leica FL400 | Different |
| Manufacturer | Carl Zeiss Meditec AG<br>Goeschwitzer Strasse 51-52<br>D-07745 Jena, Germany | Leica Microsystems<br>(Schweiz) AG | Different |
| Classification Product<br>Code | QFX | QFX | Identical |
| Regulation # | 21 CFR 882.4950 (Diagnostic<br>neurosurgical microscope<br>filter) | 21 CFR 882.4950<br>(Diagnostic neurosurgical<br>microscope filter) | Identical |
| Fluorescence<br>Excitation Spectral<br>Window | 400 nm - 430 nm | 380 – 430 nm | Equivalent for<br>fluorescence agent |
| Spectrum of the<br>Emission Filter | 430 - 800 nm | 300 – 1100 nm | Equivalent for<br>detecting the<br>fluorescence agent |
| Combination Device | No | No | Identical |
| Visualization Result | Fluorescent image of<br>distribution of the<br>accumulated protoporphyrin<br>IX (PpIX) in malignant tissue<br>during operation. | Fluorescent image of<br>distribution of the<br>accumulated protoporphyrin<br>IX (PpIX) in malignant tissue<br>during operation. | Identical |
| Visualization of Real-<br>Time Images | Yes | Yes | Identical |
| Visualization on<br>Interface/Display | Yes | Yes | Identical |
| Light Specifications –<br>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 the<br>Illumination Source | The irradiance spectrum (250 nm - 1020 nm,<br>mW/cm^2) of the illumination source was<br>measured and verified with a spectrometer. These<br>measurements were assessed prior to application of<br>the excitation filter module. | Passed |
| Maximum Power and<br>Irradiance of the<br>Illumination Source | The maximum output power and irradiance of<br>illumination sources were measured and verified<br>with a power meter at the end of the microscope<br>light guide. These measurements were assessed<br>prior to application of the excitation filter module. | Passed |
| Irradiance Spectrum of<br>the Excitation Light and<br>Spectral Response of the<br>Excitation Filter | The irradiance spectrum (250 nm - 1020 nm) of the<br>illumination light, following passage through the<br>excitation filter module, was measured at a working<br>distance of 30 cm with a spectrometer. The edges at<br>50% decrease of the blue excitation peak were<br>calculated respectively. | Passed |
| Maximum Excitation<br>Power and Power<br>Density | The maximum power (mW) and power density<br>(mW/cm^2) of the excitation light was measured<br>with a thermopile, at multiple different working<br>distances (22.5 - 30 cm) and zoom settings,<br>including the maximum and minimum zoom.<br>The power density measurements of the subject<br>device were compared to the predicate device. | Passed |
| Optical Path Loss | To determine the overall detectable light output and<br>the total losses in relation to device working<br>distance and zoom setting, optical path loss was<br>calculated by dividing the output signal measured at<br>the microscope eyepiece (without emission filter)<br>by the illumination signal measured with a<br>spectrometer at the microscope focal plane for the<br>same zoom setting. A reflection standard (white<br>silicon remission disc) was used at a working<br>distance of 35 cm. | Passed |
| Spectrum of the<br>Emission Filter | The spectrum (350 nm - 1050 nm) of the emission<br>filter 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 spectroradiometer<br>to include all the coating and optics that affects the<br>spectrum of the observation path. For this test the<br>excitation filter was removed, and a reflection<br>standard was used at the device focal plane with<br>different zoom settings. To compare the light that<br>passes the observation optics and emission filter,<br>the 50% edge of the spectrum was calculated. | Passed |
| Homogeneity of the<br>Excitation Light at the<br>Focal Point | The reflected signal from a white sheet of paper<br>positioned at 30 cm working distance was imaged<br>by the surgical operating microscope camera and<br>the intensity profile was calculated to demonstrate<br>the homogeneity of the excitation light. | Passed |
| System Sensitivity | As a diffusely reflecting and fluorescent disc the<br>ZEISS BLUE 400 fluorescent target was used and<br>positioned at a microscope working distance of 22.5<br>cm. The zoom setting was chosen to lead to the<br>same image size of the target for all three devices. | Passed |
| | The fluorescence signal in the eyepiece of the<br>subject device was compared to the predicate<br>device. | |
| Pre-Operative Phantom<br>Test | This test was conducted to demonstrate that the<br>ZEISS BLUE 400 test phantom is suitable for the<br>pre-operative checks of the KINEVO 900 and<br>OPMI PENTERO 900. The phantom has one<br>fluorescent area and was imaged by the surgical<br>microscope camera. The same test was repeated by<br>observation through the microscope eyepiece. | Passed |
| Spectrum of Camera<br>Filter | The spectrum at the camera interface was measured<br>with a spectroradiometer to demonstrate that<br>camera filter can block near infrared and infrared<br>leakage 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.
