(91 days)
The Aperio ePathology eIHC IVD System is an automated digital slide creation, management, viewing and analysis system. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting and classification of tissues and cells of clinical interest based on particular color, intensity, size, pattern and shape.
The IHC HER2 Image Analysis application is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in formalin-fixed, paraffin-embedded neoplastic tissue.
The IHC HER2 Image Analysis application is intended for use as an accessory to the Dako HercepTest™ to aid in the detection and semi-quantitative measurement of Her2/neu (c-erbB-2) in formalin-fixed, paraffin-embedded neoplastic tissue. When used with the Dako HercepTest™, it is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN®(Trastuzumab) treatment is being considered.
The IHC ER Image Analysis application is intended for use as an aid to the pathologist in the detection and quantitative measurement of ER (Estrogen Receptor) in formalin-fixed paraffin-embedded neoplastic tissue.
The IHC PR Image Analysis application is intended for use as an aid to the pathologist in the detection and quantitation measurement of PR (Progesterone Receptor) in formalin-fixed, paraffin-embedded neoplastic tissue.
lt is indicated for use as an aid in the management, prognosis, and prediction of therapy outcomes of breast cancer.
The Aperio ePathology eIHC IVD System ("System") is an automated digital slide creation, management, viewing and analysis system. The Aperio ePathology eIHC IVD System components consist of an automated digital microscope slide scanner, computer, color monitor, keyboard and digital pathology information management software. The system capabilities include digitizing microscope slides at high resolution, storing and managing the resulting digital slide images, retrieving and displaying digital slides, including support for remote access over wide-area networks, providing tools for annotating digital slides and entering and editing data associated with digital slides, and tools for image analysis of digital slides. Image analysis capabilities include the ability to quantify characteristics useful to Pathologists, such as measuring and scoring immunohistochemical stains applied to histology specimens, including the Dako HerceptTest™, Dako ER/PR, which reveal the presence of proteins such as Human Epidermal growth factor Receptor 2 (HER2), ER (Estrogen Receptor) protein and PR (Progesterone Receptor) protein expression.
Below summarizes the acceptance criteria and study information for the Aperio ePathology eIHC IVD System, specifically for its HER2, ER, and PR Image Analysis applications.
1. Table of Acceptance Criteria and Reported Device Performance
For IHC HER2 Image Analysis:
| Acceptance Criteria (Agreement with Predicate Device) | Reported Device Performance (Exact 95% Lower Confidence Interval) |
|---|---|
| Percent agreement (trichotomous: 0 & 1+, 2+, 3+) | Passed acceptance criteria |
For IHC ER and PR Image Analysis:
| Acceptance Criteria (Agreement with Predicate Device) | Reported Device Performance (Exact 95% Lower Confidence Interval) |
|---|---|
| Percent agreement (dichotomous: Positive vs Negative at 1% and 10% thresholds) | Passed acceptance criteria |
2. Sample Size and Data Provenance for Test Set
- Sample Size: Not explicitly stated for either HER2 or ER/PR. The document mentions "slides represented the range of HER2 scores (0, 1+, 2+ and 3+)" and "slides represented the range of ER and PR scores that are observed clinically."
- Data Provenance: The samples were "Paraffin embedded breast tissue slides prepared with the appropriate Dako HER2 IHC test kit" and "Paraffin embedded breast tissue slides prepared with the appropriate Dako ER and PR IHC test kits." The origin (e.g., country) is not specified. The studies were internal system performance tests, implying a retrospective nature where pre-existing clinical samples were used.
3. Number of Experts and Qualifications for Ground Truth
- The document states that the HER2, ER, and PR scores obtained from the updated ScanScope systems were "evaluated for concordance with the scores obtained from the predicate device." This suggests the predicate device's scores served as the reference for comparison, rather than human experts directly establishing ground truth for the test set in these specific performance studies.
- No information is provided about the number or qualifications of experts directly establishing ground truth for the test set used in the system performance testing. The predicate device's output was the reference.
4. Adjudication Method
- Not applicable as the comparison was against the predicate device's scores, not human expert consensus requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done. The studies described were system-level performance tests evaluating the updated ScanScope instruments against a predicate device.
- Therefore, no effect size of human readers improving with AI vs. without AI assistance is provided. The device is intended as an "adjunctive computer-assisted methodology to assist the reproducibility of a qualified pathologist."
6. Standalone Performance Study
- Yes, a standalone study (algorithm-only performance) was conducted. The "System Performance Testing" described for both HER2 and ER/PR evaluated the "accuracy of the HER2 image analysis algorithm on the updated ScanScope instruments" and "accuracy of the ER and PR image analysis algorithms on the updated ScanScope instruments," respectively, by comparing their output against the predicate device's scores.
7. Type of Ground Truth Used
- For the system performance testing, the ground truth used was the scores obtained from the legally marketed predicate device (ScanScope XT). The updated ScanScope models' results were evaluated for concordance with the predicate device's scores.
8. Sample Size for the Training Set
- The document does not provide information regarding the sample size specifically used for training the image analysis algorithms. The described studies are performance evaluations of the already developed algorithms.
9. How Ground Truth for Training Set was Established
- The document does not provide information on how the ground truth for the training set was established. The focus of this submission is on the direct comparison of the updated devices' performance to the predicate device.
§ 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.