(335 days)
The Leica FL400 is a surgical microscope accessory filter set for viewing fluorescence of fluorophores comprising an excitation filter for blue spectral range 380 mm - 430 nm and an observation filter comprising the long-wave blue, green, yellow and red spectrum in the spectral band greater than 444 nm.
The FL400 is a surgical microscope accessory used in fluorescent visualization of suspected grade III or IV gliomas during neurosurgery.
The Leica FL400 is a fluorescence accessory that consists of an excitation (illumination) filter module and an emission (observation) filter module that are intended to be inserted into the optical beam path of compatible Leica surgical operating microscopes models M525 and M530. The excitation filter (380 nm - 430 nm), when placed into the light path, provides a fluorescence excitation light system for use in conjunction with an approved fluorophore selective for grade III or IV malignant gliomas.
The emission filter is a long pass filter allowing light wavelengths greater than 444 nm to pass. The fluorophore emits light at a longer wavelength than the excitation light. Once passed through the emission filter module, a camera adapted to the surgical microscope detects the fluorescence signal, allowing the user to visualize the fluorophore in the open neurosurgery field.
The Leica FL400 is supplied with a test phantom to confirm proper pre-operative fluorescence set-up. The Leica FL400 Test Phantom offers multiple levels of fluorescence intensity, which provides the clinician with a visual assessment of the FL400 pre-operative set-up. The clinician is advised to confirm the fluorescence spots are visible to confirm functionality prior to utilization.
Here's a breakdown of the acceptance criteria and the study that proves the Leica FL400 meets those criteria, based on the provided text:
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Special Controls) | Reported Device Performance and How it Meets the Criteria |
|---|---|
| 1. Non-clinical performance testing demonstrates that the device performs as intended under anticipated conditions of use, and verify and validate filter specifications and functional characteristics, including: | Non-clinical bench testing was performed to verify device specifications for proper visualization of fluorescing agents. This testing addressed all the sub-points below. |
| (i) Spectrum and intensity of the illumination source; | - Spectrum of the Illumination Source: The irradiance spectrum (300 nm - 1100 nm, . mW/cm2) of the illumination source was measured and verified with a spectrometer prior to application of the excitation filter module. |
- Maximum Power and Irradiance of the Illumination Source: The maximum output power and irradiance were measured with a power meter at the end of the microscope light guide prior to application of the excitation filter module. |
| (ii) Spectrum of the excitation and emission filter modules when integrated in the surgical operating microscope; | - Irradiance Spectrum of the Excitation Light and Spectral Response of the Excitation Filter: The irradiance spectrum (300 nm - 1100 nm) of the illumination light, following passage through the excitation filter module, was measured at working distances of 30 cm (M525) and 35 cm (M530) with a spectrometer. The spectral response of the excitation filter was derived by dividing this by the illumination source spectrum without the filter. - Spectrum of the Emission Filter: The spectrum (300 nm – 1100 nm) of the emission filter when integrated in the surgical operating microscope was measured, including all coatings and optics. Transmission of the emission filter was calculated from white light remission spectra. |
| (iii) Excitation power and power density; | - Maximum Excitation Power and Power Density: The maximum power (mW) and power density (mW/cm²) of the excitation light was measured with a thermopile and UV diode at multiple working distances and zoom settings. These measurements were compared to excitation power densities observed in clinical trials assessing fluorophore efficacy. |
| (iv) Optical path loss from illumination source to objective lens or microscope camera; | - Optical Path Loss: Calculated by dividing the output signal measured at the microscope eyepiece (without emission filter) by the illumination signal measured at the microscope focal plane for the same zoom setting, using a reflection standard. |
| (v) Homogeneity of the excitation light at the focal plane; | - Homogeneity of the Excitation Light at the Focal Point: The reflected signal from a white sheet of paper was imaged by the surgical operating microscope camera, and the intensity profile was calculated to demonstrate homogeneity. |
| (vi) Fluorescence detection sensitivity; | - System Sensitivity: A diffusely reflecting and fluorescent silicone disc was positioned at 30 cm working distance. The device output spectrum was measured by a spectrometer at the microscope eyepiece for different zoom settings. The fluorescence/remission ratio was calculated. |
| (vii) Verification of calibration or pre-operative procedures; | - Pre-Operative Phantom Test: This test demonstrated that the Leica FL400 test phantom is suitable for pre-operative checks. The phantom, with 4 dots of different fluorophore concentrations, was imaged by the camera and observed through eyepieces at different working distances and zoom settings. |
| (viii) If camera-based, spectral sensitivity of the camera. | - Spectrum of Camera Filter: Measured to demonstrate that it can block near infrared and infrared leakage of excitation light to the camera. This implies the camera's filter sensitivity is appropriate for the system. |
Study Details
The provided document describes no clinical studies for the Leica FL400 itself. The special controls and the benefit-risk determination rely entirely on non-clinical/bench studies to demonstrate the device's technical performance and its compatibility with an existing, FDA-approved fluorophore (aminolevulinic acid hydrochloride - ALA HCl). The efficacy of ALA HCl was demonstrated in prior clinical studies for which the Leica FL400 effectively acts as a visualization system with compatible spectral characteristics.
Here's the information requested based on the provided text:
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Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- Test Set Sample Size: Not applicable. No clinical test sets were used for the Leica FL400 device performance. The bench tests involved various optical measurements and simulated scenarios (e.g., test phantom, white reflection standard).
- Data Provenance: Not applicable for clinical data. The non-clinical/bench testing was performed by the manufacturer, Leica Microsystems (Schweiz) AG. The source of the clinical data for ALA HCl is referenced as FDA's Center for Drug Evaluation and Research (CDER) under NDA 208630, which would generally be multi-national and prospective, but this pertains to the fluorophore, not the device's clinical performance.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
- Not applicable. As no clinical studies were performed for the Leica FL400, no experts were needed to establish ground truth for a clinical test set. The technical specifications and measurements from bench testing serve as the "ground truth" for the device's optical performance.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. There was no clinical test set requiring expert adjudication.
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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. An MRMC comparative effectiveness study was not done. The Leica FL400 is a hardware accessory (filter set), not an AI-assisted diagnostic tool.
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If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Not applicable. The Leica FL400 is not an algorithm. It's a filter set that requires a human neurosurgeon to interpret the visualized fluorescence through a microscope.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- For the Leica FL400, the "ground truth" for its performance is derived from physical measurements and engineering specifications obtained during bench testing. For example, measured spectra, power densities, and calculated optical path losses are compared to design specifications and relevant external data (e.g., fluorophore characteristics).
- The clinical efficacy of the fluorophore (ALA HCl) that the FL400 is designed to visualize was established based on clinical studies with ground truth likely derived from histopathology (for positive predictive value) and potentially adjudicated clinical follow-up/outcomes (for negative predictive value limitations), as described in the summary stating "PPV ranged from 96% to 98%" and "NPV ranged from 19% to 24%." However, this is for the drug, not the device.
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The sample size for the training set:
- Not applicable. The Leica FL400 is a hardware device (filter set), not an AI algorithm. There is no training set in this context.
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How the ground truth for the training set was established:
- Not applicable. There is no training 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.