(24 days)
The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.
The Virtuoso™ System for IHC ER (SPI) is for digital read and image analysis applications. This particular Virtuoso system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody assay. The CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment). For prescription use only.
Note: The IHC ER (SP1) Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specimens stained for the presence of ER protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the quality of the immunohistochemical staining. If is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody used to assure the validity of the Virtuoso System for IHC ER Digital Read and Image Analysis scores.
The Virtuoso™ System is an instrument-plus-software system designed to assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemically stained histologic sections from formalin-fixed, paraffin-embedded normal and neoplastic tissues. The system consists of a slide scanner (iScan), computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Windows web browser-based user interface. Virtuoso is a web-based, end-to-end, digital pathology software solution that allows pathology laboratories to acquire, manage, view, analyze, share, and report digital images of pathology specimens. Using the Virtuoso software, the pathologist can view digital images, add annotations, make measurements, perform image analysis, and generate reports.
The iScan slide scanning device captures digital images of formalin-fixed, Hardware: paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide scanner, racks for loading glass slides, computer, scanner software, keyboard, mouse and monitor.
The Virtuoso software is designed to complement the routine workflow of a Software: qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.
Here's a breakdown of the acceptance criteria and the study details for the Virtuoso™ System for IHC ER (SP1), based on the provided document:
Acceptance Criteria and Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Digital Read vs. Manual Read | |
| Minimum Total Agreement (Overall Percent Agreement) ≥ 75% | 98.2% (93.7-99.5% CI) |
| Image Analysis Read vs. Manual Read | |
| Minimum Total Agreement (Overall Percent Agreement) ≥ 75% | 91.0% (84.2-95.0% CI) |
Study Details
2. Sample Size and Data Provenance
- Test Set Sample Size: 111 evaluable cases.
- Data Provenance: Not explicitly stated, but the study was conducted at "one site," which implies a single-center study. The text doesn't specify the country of origin, nor whether it was retrospective or prospective, though the nature of "available from the original study" and "blinding" suggests a retrospective analysis of previously collected samples.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: One pathologist.
- Qualifications: "one pathologist," no further specific qualifications (e.g., years of experience, subspecialty) are provided in the document.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. The study used a single pathologist to establish the manual microscopic read as the reference (ground truth). Discrepancies between the digital read/image analysis and the manual read were directly evaluated against this single reference, rather than being arbitrated by multiple experts.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- MRMC Study Done?: No. The study evaluated agreement of the system with one pathologist's manual reads and did not assess improvement of human readers with AI assistance. The study design involved the same pathologist scoring cases in three different ways (manual, digital, image analysis) in a blinded fashion.
6. Standalone Performance (Algorithm Only)
- Standalone Performance Done?: Yes, to an extent. The "Image Analysis Read" directly reflects the algorithm's performance, which was then compared to the manual read. The "digital read" also represents a form of standalone performance where the pathologist reviews the digital image without the algorithm's quantitative output. Both were compared to the manual microscopic read.
7. Type of Ground Truth Used
- Type of Ground Truth: Expert consensus (from a single pathologist) on manual microscopic examination. The document explicitly states, "The manual score (reference result) was compared to both the digital read result and the image analysis result."
8. Sample Size for the Training Set
- Training Set Sample Size: Not specified in this document. The document describes the validation study for the device. Information about the training set size would typically be found in the device's development or internal validation reports, not usually detailed in a 510(k) summary focused on demonstrating substantial equivalence.
9. How Ground Truth for the Training Set Was Established
- Ground Truth Establishment for Training Set: Not specified in this document. Similar to the training set size, the method for establishing ground truth for training data is usually part of the algorithm's development process and not typically detailed in this type of regulatory submission.
§ 864.1860 Immunohistochemistry reagents and kits.
(a)
Identification. Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.(b)
Classification of immunohistochemistry devices. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these devices are exempt from the premarket notification requirements in part 807, subpart E of this chapter. This exemption applies to IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding. These IHC's are used after the primary diagnosis of tumor (neoplasm) has been made by conventional histopathology using nonimmunologic histochemical stains, such as hematoxylin and eosin. Examples of class I IHC's are differentiation markers that are used as adjunctive tests to subclassify tumors, such as keratin.(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.
(3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section.
(c)
Date of PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the Federal Food, Drug, and Cosmetic Act is required for any device described in paragraph (b)(3) of this section before this device may be commercially distributed. See § 864.3.