(154 days)
BLUE 400 and BLUE 400 S are accessories to the surgical microscope and allow the fluorescence observation of fluorophores with an excitation peak between 400 nm and the fluorescence emission observation comprising the spectrum in a spectral band of 620 - 710 nm.
The ZEISS BLUE 400 and BLUE 400 S are surgical microscope accessories used in fluorescent visualization of suspected grade III and IV gliomas during neurosurgery.
The BLUE 400 and BLUE 400 S are fluorescence accessories to qualified surgical microscopes, intended to allow intraoperative viewing of malignant glioma tissue grade III and IV under fluorescence. The overall system is comprised of excitation (illumination) and emission (observation) filters to detect fluorescence and are optimized in conjunction with the drug to pass light between 620 – 710 nanometers. The BLUE 400 S filters allow the surgical microscope to produce excitation light in a wavelength range covering at least 400 - 410 nanometers that excites an approved optical imaging agent and enables the surgeon to observe the emitted fluorescent signal in the oculars or on a display. Fluorescence of marked brain tissue helps visualization of tissue associated with Grade III & IV glioma during neurosurgeries.
Compared to the blue visualization of the surrounding non-fluorescent tissue in the BLUE 400 image, BLUE 400 S is designed to visualize the surrounding nonfluorescent tissue more similar to white light impression, while tumor visualization of grade III and IV glioma remains consistent. With the visualization of non-fluorescent anatomy in an almost white light impression, BLUE 400 S is expected to allow PplX visualization with less frequent switching between fluorescence and white light imaging modes.
BLUE 400 and BLUE 400 S can be installed only into qualified ZEISS surgical microscopes. For these accessories to be used with a qualified ZEISS surgical microscope, the critical components of the surgical microscope need to fulfill the clinically relevant parameters for the Indications for Use of BLUE 400 and BLUE 400 S.
The provided FDA 510(k) summary (K240215) describes the Carl Zeiss Meditec AG BLUE 400 and BLUE 400 S accessories to surgical microscopes for fluorescent visualization of grade III and IV gliomas.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The submission primarily focuses on demonstrating substantial equivalence to a predicate device (BLUE 400, K211346) through technical and performance testing, rather than defining explicit clinical acceptance criteria in terms of sensitivity, specificity, or other diagnostic measures for identifying gliomas. The acceptance criteria used are in the form of "Passed" results for various technical and functional tests.
| Test Description | Acceptance Criteria (Implied by "Passed" result) | Reported Device Performance |
|---|---|---|
| Brightness of the fluorescence ocular image | Image brightness of ZEISS fluorescence target at ocular plane at 250 mm working distance meets specified target. (Specific value not provided here, but "Passed") | Passed |
| Irradiance | Excitation light density in the object plane meets specified target. (Specific value not provided here, but "Passed") | Passed |
| Spatial resolution of the ocular image | Spatial resolution measured with test target in white light mode at min/max magnification and 200mm working distance meets specified target. (Specific value not provided here, but "Passed") | Passed |
| Excitation wavelength (of the microscope) | Excitation wavelength range of PpIX (400 nm to 410 nm) is covered by both BLUE 400 and BLUE 400 S options. (Specific quantitative range achieved for subject device: BLUE 400: 400-430nm; BLUE 400 S: 398-457nm for 50% edges) | Passed |
| Excitation filter | Optical filter specification of excitation filter meets requirements. | Passed |
| Emission wavelength (of the microscope - ocular image) | Design review/measurement of spectrum at ocular plane meets requirements. (Specific quantitative range achieved for subject device: BLUE 400: >450nm; BLUE 400 S: 540-728nm for 50% edges) | Passed |
| Emission wavelength (of the microscope - video image) | Design review/measurement of spectrum at ocular plane meets requirements. | Passed |
| Emission filter | Optical filter specification of emission filter meets requirements. | Passed |
| Non-mirrored video image | Visual inspection with test target in white light mode confirms non-mirrored image. | Passed |
| Non-rotated video image | Visual inspection with test target in white light mode confirms non-rotated image. | Passed |
| Non-deformed video image | Visual inspection of geometric distortions of a test target with a circle in white light mode shows no significant deformation. | Passed |
| Centered video image | Visual inspection and measurement with a test target in white light mode confirms centered image. | Passed |
| Photometric resolution of video image | Grey value resolution test with photometric resolution test target in white light mode meets requirements. | Passed |
| Signal-to-noise ratio of the video image (sensitivity) | Signal-to-noise ratio of video image of a fluorescent target at a given signal value meets requirements. | Passed |
| Latency of the video image | Video latency in white light mode meets requirements. | Passed |
| Spatial resolution of the video image | Spatial resolution measured with test target in white light mode meets requirements. | Passed |
| Spectrum of the Illumination Source (TS1) | Irradiance spectrum (250 nm - 1020 nm, mW/cm²) of illumination source measured and verified with spectrometer prior to excitation filter module application. | Passed |
| Maximum Power and Irradiance of the Illumination Source (TS2) | Maximum output power and irradiance of illumination sources measured and verified with power meter at end of microscope light guide prior to excitation filter module application. | Passed |
| Irradiance Spectrum of the Excitation Light and Spectral Response of the Excitation Filter (TS3) | Irradiance spectrum (250 nm - 1020 nm) of illumination light after excitation filter module measured; 50% decrease edges of blue excitation peak calculated and found acceptable. | Passed |
| Maximum Excitation Power and Power Density (TS4) | Maximum power (mW) and power density (mW/cm²) of excitation light measured at multiple working distances/zoom settings. Subject device measurements comparable to predicate device. | Passed |
| Optical Path Loss (TS5) | Detectable light output and total losses in relation to device working distance and zoom setting, calculated by dividing output signal at eyepiece by illumination signal at focal plane for the same zoom setting, found acceptable. | Passed |
| Spectrum of the Emission Filter (TS6) | Spectrum (350 nm – 1050 nm) of emission filter integrated in surgical microscope measured; 50% edge of spectrum calculated and found acceptable. | Passed |
| Homogeneity of the Excitation Light at the Focal Point (TS7) | Reflected signal from white sheet of paper at 30 cm working distance imaged, and intensity profile calculated to demonstrate homogeneity of excitation light, found acceptable. | Passed |
| System Sensitivity (TS8) | BLUE 400: Fluorescence signal in eyepiece for ZEISS BLUE 400 fluorescent target at 22.5 cm working distance comparable to predicate device. BLUE 400 S: Ratio of reconstructed fluorescence signal to reconstructed remission spectrum (corresponding to fluorescence to emission light ratio) found acceptable. (Specific details of "acceptable" criteria are not provided) | Passed |
| Pre-Operative Phantom Test (TS9) | ZEISS BLUE 400 test phantom (with one fluorescent area) suitable for pre-operative checks of a surgical microscope; imaged by camera and observed through eyepiece. | Passed |
| Spectrum of the Camera Filter (TS10) | Spectrum at camera interface measured to demonstrate camera filter blocks near infrared and infrared leakage of excitation light to the camera. | Passed |
| Special Controls Testing | Performance with and without cover glass met defined specifications. | Passed |
2. Sample Size Used for the Test Set and Data Provenance
The document describes non-clinical performance testing (bench testing) using "ZEISS fluorescence target," "spatial test target," "photometric resolution test target," "test target with a circle," "white sheet of paper," and "ZEISS BLUE 400 test phantom."
- Sample Size: Not explicitly stated for each test, but implied to be sufficient for bench validation of optical and system parameters. These are physical components being tested, not patient samples.
- Data Provenance: The tests are described as bench/non-clinical system testing. This indicates the data was generated in a lab setting by the manufacturer (Carl Zeiss Meditec AG, Germany, based on manufacturer details). It is not derived from patient data.
- Retrospective/Prospective: Not applicable as it's bench testing, not clinical studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Not applicable. This submission relies on technical bench testing against predefined engineering specifications and comparison to a legally marketed predicate device. The "ground truth" for these tests is the physical measurement of optical properties and system functions, validated against engineering requirements, not clinical expert consensus on patient data.
4. Adjudication Method for the Test Set
- Not applicable. Adjudication methods like "2+1" or "3+1" are typically used in clinical studies for establishing ground truth (e.g., determining disease presence in an image) based on multiple readers. This submission describes bench testing where the outcome is a "Passed" result based on meeting physical specifications.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not done. The submission focuses on non-clinical technical equivalence and performance of the device's optical and system functions. It does not evaluate human reader performance with or without AI assistance. The device itself (BLUE 400/BLUE 400 S) is a filter accessory, not an AI-powered diagnostic tool aiming to improve reader interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- No, a standalone algorithm performance study was not done. This device is an accessory to a surgical microscope. It enhances visualization for a human surgeon; it is not a standalone algorithm that provides diagnoses or interpretations. The software verification testing mentioned is for the device's control software, not a diagnostic algorithm.
7. The Type of Ground Truth Used
- The "ground truth" for the performance testing is engineering specifications and measurements of optical, electrical, and mechanical properties. For example, excitation wavelength range is validated against the known excitation peak of PpIX, and image properties (resolution, brightness, lack of deformation) are validated against defined standards for surgical microscopes. The comparison to the predicate device also serves as a benchmark for equivalence.
8. The Sample Size for the Training Set
- Not applicable. The BLUE 400 and BLUE 400 S are physical filter accessories for a surgical microscope, not an AI/machine learning device that requires a training set. The software mentioned is for the device's operation and control, not for image analysis or diagnostic inference that would necessitate a training set.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. As the device is not an AI/ML system requiring a training set, there is no ground truth established for such a set.
§ 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.