(192 days)
Not Found
No
The description focuses on manual examination of digital slides by a pathologist, with image analysis capabilities mentioned but not explicitly described as using AI/ML. The performance studies also focus on pathologist agreement and a separate image analysis algorithm, but there is no indication that this algorithm utilizes AI/ML. The "Mentions AI, DNN, or ML" section is marked "Not Found".
No.
Explanation: The device is described as an aid to the pathologist for diagnosis and assessment of therapy outcomes, but it does not directly administer treatment or function as a therapeutic modality itself.
Yes
The "Intended Use / Indications for Use" section explicitly states that the system is "intended for in vitro diagnostic use as an aid to the pathologist." It also mentions its use aid in the "detection and semi-quantitative measurement of HER-2/neu" for "management, prognosis and prediction of therapy outcomes of breast cancer," which are all diagnostic purposes.
No
The device description explicitly states that the ScanScope® System components include an automated digital microscope slide scanner, computer, color monitor, and keyboard, in addition to the software. This indicates it is a system with both hardware and software components, not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use Statement: The very first sentence of the "Intended Use / Indications for Use" section explicitly states: "It is intended for in vitro diagnostic use as an aid to the pathologist..."
- Clinical Context: The intended use describes the system's role in aiding pathologists in the display, detection, counting, and classification of tissues and cells of clinical interest. This directly relates to diagnosing or aiding in the diagnosis of diseases.
- Specific Application: The IHC HER2 Manual Read of Digital Slides application is specifically intended for use as an aid in the detection and semi-quantitative measurement of HER-2/neu, which is a crucial marker in the management, prognosis, and prediction of therapy outcomes for breast cancer. This is a clear clinical application.
- Accessory to an IVD: The application is also described as an accessory to the Dako HercepTest™, which is an FDA-approved IVD (indicated by the K number P980018). Accessories to IVDs are generally considered IVDs themselves when they are essential for the proper functioning and intended use of the primary IVD.
- Device Description: The device description reinforces its use in a clinical setting by mentioning its capabilities for digitizing microscope slides, storing and managing digital slide images, and supporting remote access for pathologists to make "clinically relevant decisions analogous to those they make using a conventional microscope."
- Performance Studies: The performance studies described are typical for IVD devices, focusing on method comparison with a predicate device and analytical performance (precision and reproducibility) in a clinical context.
In summary, the device's intended use, specific applications, role as an accessory to an existing IVD, and the nature of the performance studies all strongly indicate that it is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The ScanScope® 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 Manual Read of Digital Slides application is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER-2/neu (cerbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor. HER2 results are indicated for use as an aid in the management, prognosis and prediction of therapy outcomes of breast cancer.
The IHC HER2 Manual Read of Digital Slides application is intended for use as an accessory to the Dako HercepTest™ to aid the pathologist in the detection and semiquantitative measurement of HER-2/neu (cerbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor. 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. Note: The actual correlation of the Dako HercepTest™ to Herceptin® clinical outcome has not been established.
Product codes (comma separated list FDA assigned to the subject device)
NOT, OEO
Device Description
System: The ScanScope ® System is an automated digital slide creation, management, viewing and analysis system. The ScanScope® 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 facilities for annotating digital slides and entering and cditing metadata associated with digital slides, and facilities for image analysis of digital slides. Image analysis capabilities include the ability to detect and quantify characteristics useful to Pathologists, such as detecting and quantifying certain proteins revealed by immunohistochemical stains applied to histology specimens. The remote digital slide viewing capabilities of the system support reading digital slides on a computer monitor, enabling Pathologists to make clinically relevant decisions analogous to those they make using a conventional microscope. Specifically, the system supports the pathologist in the detection and semi-quantitative measurement of HER-2/neu (cerbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor.
Hardware Operation: The ScanScope® XT digital slide scanner creates high resolution, color digital slide images of entire glass slides in a matter of minutes. High numeric aperture 20x or 40x objectives, as found on conventional microscopes, are used to produce high-quality images. The ScanScope XT employs a linear-array scanning technique that generates digital slide images that have no tiling artifacts and that are essentially free from optical aberrations along the scanning axis.
Software Operation: The Spectrum™ software is a full-featured digital pathology information management system. The software runs on a server computer called a Digital Slide Repository (DSR), which stores digital slide images on disk storage such as a RAID array, and which hosts an SQL database that contains digital slide metadata. Spectrum includes a web application and services which encapsulate database and digital slide image access for other computers. The Spectrum server supports the capability of running a variety of digital slide image analysis algorithms on digital slides, and storing the results of analysis into the database. Spectrum also includes support for locally or remotely connected image workstation computers, which run digital slide viewing and analysis software provided as part of Spectrum.
Overview of System Operation: The laboratory technician or opcrator loads glass microscope slides into a specially designed slide carrier with a capacity of up to 120 slides. The scanning process begins when the operator starts the ScanScope® scanner and finishes when the scanner has completed scanning of all loaded slides. As each glass slide is processed, the system automatically stores individual "striped" images of the tissue contained on the glass slide and integrates the striped images into a single digital slide image, which represents a histological reconstruction of the entire tissue section. After scanning is completed, the operator is able to view, interpret and perform certain analytical tests on the digital slides.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Microscopic Digital Slide Images
Anatomical Site
Breast tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Pathologist / Clinical setting (implied by clinical workflow distribution)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A total of one-hundred and eighty (180) formalin-fixed, paraffin-embedded breast tissue specimens from two (2) clinical sites were used for this study; eighty (80) specimens from the first clinical site with an approximately equal distribution of slides for the different HER2 scores (0, 1+, 2+, 3+) and one-hundred (100) specimens from the second clinical site taken from their clinical operation, representing the typical workflow distribution of cases encountered in a clinical setting. All specimens were immunohistochemically stained using Dako's FDA approved HerceptTest™ (P980018).
Three (3) different Pathologists at cach clinical site performed a blinded manual examination of each glass slide using a conventional light microscope in accordance with the reagents' instructions for use. The Pathologists reported the HER2 scores of 0, 1+, 2+ or 3+ for cach of the glass slides examined. The glass slides from each of the two clinical sites respectively were scanned using a different ScanScope® scanner instrument. After a wash-out period of over one (1) week and subsequent randomization of the slides, the same three (3) Pathologists at each clinical site performed a blinded manual read of each digital slide displayed on a computer monitor using the ScanScope XT System's remote viewing capability. The Pathologists reported a HER2 score of 0, 1+, 2+ or 3+ for each of the digital slides corresponding to their respective clinical site.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Comparison studies:
Method comparison with predicate device:
The method comparison study was performed to compare the manual examination or “reading” of digital slides on a computer monitor (hereinafter characterized as “reading” of digital slides) to conventional manual microscopic examination of glass slides with respect to the quantification of HER2 expression in breast tissue.
Sample size: 180 formalin-fixed, paraffin-embedded breast tissue specimens (80 from first site, 100 from second site).
Key results: Statistical analyses are provided for a trichotomous categorization of the HER2 scores combining 0 and 1+ and leaving 2+ and 3+ uncombined. Percentage Agreement (PA) along with an exact 95% Confidence Interval (CI) are presented overall for all trichotomous HER2 score categories combined.
Manual Microscopy - Inter-Pathologists - Agreements:
Clinical site 1: Pathologist 1 v 2 PA 91.3% (82.8, 96.4); Pathologist 1 v 3 PA 77.5% (66.8, 86.1); Pathologist 2 v 3 PA 76.3% (65.4, 85.1).
Clinical site 2: Pathologist 1 v 2 PA 84.0% (75.3, 90.6); Pathologist 1 v 3 PA 82.0% (73.1, 89.0); Pathologist 2 v 3 PA 90.0% (82.4, 95.1).
Manual Digital Slide Reading - Inter-Pathologists - Agreements:
Clinical site 1: Pathologist 1 v 2 PA 70.0% (58.7, 79.7); Pathologist 1 v 3 PA 71.3% (60.0, 80.8); Pathologist 2 v 3 PA 71.3% (60.0, 80.8).
Clinical site 2: Pathologist 1 v 2 PA 86.0% (77.6, 92.1); Pathologist 1 v 3 PA 79.0% (69.7, 86.5); Pathologist 2 v 3 PA 77.0% (67.5, 84.8).
Manual Microscopy vs. Digital Slide Reading - same Pathologist - Agreements:
Clinical site 1: Pathologist 1 PA 61.3% (49.7, 71.9); Pathologist 2 PA 71.3% (60.0, 80.8); Pathologist 3 PA 92.5% (84.4, 97.2).
Clinical site 2: Pathologist 1 PA 85.0% (76.5, 91.4); Pathologist 2 PA 84.0% (75.3, 90.6); Pathologist 3 PA 89.0% (81.2, 94.4).
The percent agreements between the pathologists' manual microscopy and manual read of digital slides ranged from 61.3% to 92.5% with confidence bounds from 49.7% to 97.2%; the inter-pathologists agreements for manual microscopy ranged from 76.3% to 91.3% with confidence bounds from 65.4% to 96.4%.
The inter-pathologists agreements for the manual read of digital slides ranged from 70.0% to 86.0% with confidence bounds from 58.7% to 92.1%; the interpathologists agreements for manual microscopy ranged from 76.3% to 91.3% with confidence bounds from 65.4% to 96.4%.
Analytical Performance:
Precision/Reproducibility:
This precision study was not done on the manual read of the digital slides but using Aperio’s IHC HER2 image analysis algorithm.
Sample size: Eight HER2 slides (two slides per HER2 score 0, 1+, 2+ and 3+).
Intra-System: The eight HER2 slides were scanned 10 times on the same ScanScope system. Image analysis results show perfect agreement (100%) for calculated HER2 scores and overall average standard deviation of 0.69% (maximum 2.46%) and average range (maximum – minimum) of 1.22% (maximum 7.14%) for cumulative percentages of 3+, 2+ and 1+ cells across all runs.
Inter-Day/Intra-System: The eight HER2 slides were scanned on the same ScanScope system over 20 times on different days. Image analysis results show perfect agreement (100%) for calculated HER2 scores and overall average standard deviation of 0.67% (maximum 2.43%) and average range of 1.68% (maximum 12.07%) for cumulative percentages of 3+, 2+ and 1+ cells across all runs.
Inter-System: The same eight HER2 slides were scanned 10 times on three different ScanScope systems. Image analysis results show perfect agreement (100%) for calculated HER2 scores across all systems and all runs. Image analysis results on each of the three ScanScope systems show an overall average standard deviation of 0.69%, 0.59% and 0.57% (maximum 2.46%, 1.65%, 1.34%) and average range of 1.22%, 1,14% and 1.20% (maximum 7.14%, 5.09%, 4.70%) for the cumulative percentages of 3+, 2+ and 1+ cells respectively over all runs. Combined image analysis results across the three ScanScope systems show an overall average standard deviation of 0.78% (maximum 2.41%) and average range of 1.93% (maximum 8.95%) respectively for the cumulative percentages of 3+, 2+ and 1+ cells over all runs.
Intra-Pathologist: One pathologist read the same eight HER2 slides 5 times using manual microscopy and 5 times using a manual read of digital slides.
Key results: Manual microscopy results show 2 outliers out of 40 scores (5%) and manual read of digital slides results show 3 outliers out of 40 scores (7.5%).
Inter-Pathologists: Three pathologists read the same eight HER2 slides using manual microscopy and using manual read of digital slides. This used data from the clinical comparison to manual microscopy study.
Key results: Manual microscopy results show 3 outliers out of 24 scores (12.5%) and manual read of digital slides results show 5 outliers out of 24 scores (21%).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Percentage Agreement (PA) and 95% Confidence Interval (CI) for trichotomous HER2 score categories.
Standard Deviation and Range for cumulative percentages of 3+, 2+, and 1+ cells in precision studies.
Outlier percentage.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
510(k) Summary of Substantial Equivalence Aperio Technologies, Inc. (ScanScope® XT System)
21 CFR 807.92(a):
DEC 2 8 2007
21 CFR 807.92(a) (1):
Submitter's name and address:
Aperio Technologies, Inc. 1430 Vantage Court, Suite 106 Vista, CA 92081
Submitter's telephonc and fax numbers:
Phone: (760) 304-6211 Fax: (760) 304-6211
Contact person:
Kim L. Bloom Manager of Regulatory Affairs Aperio Technologies, Inc. 1430 Vantage Court, Suite 106 Vista, CA 92081 kbloom@aperio.com
Date this 510(k) summary was prepared:
November 26, 2007
21 CFR 807.92(a)(2):
| Trade Name of Device: | ScanScope® System |
|---|---|
| Regulatory Section: | 21 CFR 864.1860 Immunohistochemistry reagents and kits |
| Classification: | Class II |
| Product Code: | NOT (microscope, automated, image analysis, operator |
| intervention) |
510k Summary – 510k-2 - Rev26Nov2007 – final
1
21 CFR 807.92(a)(3): Legally marketed predicate device to which substantial equivalence is claimed:
| Predicate Device: | Automated Cellular Imaging System ("ACIS") and ACIS HER2
software application |
|-------------------|----------------------------------------------------------------------------------|
| Manufacturer: | ChromaVision Medical Systems, Inc. |
Predicate Device k#: K032113
21 CFR 807.92(a)(4): Description of the device that is the subject of this premarket notification:
System: The ScanScope ® System is an automated digital slide creation, management, viewing and analysis system. The ScanScope® 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 facilities for annotating digital slides and entering and cditing metadata associated with digital slides, and facilities for image analysis of digital slides. Image analysis capabilities include the ability to detect and quantify characteristics useful to Pathologists, such as detecting and quantifying certain proteins revealed by immunohistochemical stains applied to histology specimens. The remote digital slide viewing capabilities of the system support reading digital slides on a computer monitor, enabling Pathologists to make clinically relevant decisions analogous to those they make using a conventional microscope. Specifically, the system supports the pathologist in the detection and semi-quantitative measurement of HER-2/neu (cerbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor.
Hardware Operation: The ScanScope® XT digital slide scanner creates high resolution, color digital slide images of entire glass slides in a matter of minutes. High numeric aperture 20x or 40x objectives, as found on conventional microscopes, are used to produce high-quality images. The ScanScope XT employs a linear-array scanning technique that generates digital slide images that have no tiling artifacts and that are essentially free from optical aberrations along the scanning axis.
Software Operation: The Spectrum™ software is a full-featured digital pathology information management system. The software runs on a server computer called a Digital Slide Repository (DSR), which stores digital slide images on disk storage such as a RAID array, and which hosts an SQL database that contains digital slide metadata. Spectrum includes a web application and services which encapsulate database and digital slide image access for other computers. The Spectrum server supports the capability of
2
running a variety of digital slide image analysis algorithms on digital slides, and storing the results of analysis into the database. Spectrum also includes support for locally or remotely connected image workstation computers, which run digital slide viewing and analysis software provided as part of Spectrum.
Overview of System Operation: The laboratory technician or opcrator loads glass microscope slides into a specially designed slide carrier with a capacity of up to 120 slides. The scanning process begins when the operator starts the ScanScope® scanner and finishes when the scanner has completed scanning of all loaded slides. As each glass slide is processed, the system automatically stores individual "striped" images of the tissue contained on the glass slide and integrates the striped images into a single digital slide image, which represents a histological reconstruction of the entire tissue section. After scanning is completed, the operator is able to view, interpret and perform certain analytical tests on the digital slides.
21 CFR 807.92(a)(5): Intended use and labeled indications for use:
The ScanScope® 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 Manual Read of Digital Slides application is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER-2/neu (cerbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor. HER2 results are indicated for use as an aid in the management, prognosis and prediction of therapy outcomes of breast cancer.
The IHC HER2 Manual Read of Digital Slides application is intended for use as an accessory to the Dako HercepTest™ to aid the pathologist in the detection and semiquantitative measurement of HER-2/neu (cerbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor. 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. Note: The actual correlation of the Dako HercepTest™ to Herceptin® clinical outcome has not been established.
21 CFR 807.92(a)(6): Technological characteristics:
The design, construction, energy source and other characteristics of the ScanScope® System candidate device are considered to be substantially equivalent to the relevant
3
features of the predicate device. A summary of the technological characteristics of the ScanScope® System candidate device in comparison to the predicate device follows:
Method of cell detection. The method of cell detection is by colorimetric pattern recognition by microscopic examination of prepared cells by size, shape, hue and intensity as observed by a computer-automated, microscopic digital slide scanner system and/or by visual observation by a health care professional.
System Components. The system components comprising the ScanScope® System candidate device are substantially equivalent to those in the predicate device; i.e., a computer-automated digital microscope slide scanner, computer, color monitor, and keyboard.
Energy Source. The electrical service is 100vAC - 240vAC, 50Hz/60 Hz, 2 amp, which is similar to the predicate device electrical service requirements.
21 CFR 807.92(b): 510(k) summaries for those premarket submissions in which determination of substantial equivalence is also based on an assessment of performance data shall contain the following information:
21 CFR 807.92(b)(1): Brief discussion of nonclinical tests submitted, referenced or relied on in this premarket notification:
There are no nonclinical tests submitted, referenced or relied on in this submission.
21 CFR 807.92(b)(2): Brief discussion of clinical tests submitted, referenced or relied on in this premarket notification:
Comparison studies:
a. Method comparison with predicate device:
The method comparison study was performed to compare the manual examination or "reading" of digital slides on a computer monitor (hereinafter characterized as "reading" of digital slides) to conventional manual microscopic examination of glass slides with respect to the quantification of HER2 expression in breast tissue.
A total of one-hundred and eighty (180) formalin-fixed, paraffin-embedded breast tissue specimens from two (2) clinical sites were used for this study; eighty (80) specimens from the first clinical site with an approximately equal distribution of slides for the different HER2 scores (0, 1+, 2+, 3+) and one-hundred (100) specimens from the second clinical site taken from their clinical operation, representing the typical workflow distribution of cases encountered in a clinical setting. All specimens were immunohistochemically stained using Dako's FDA approved HerceptTest™ (P980018).
4
Three (3) different Pathologists at cach clinical site performed a blinded manual examination of each glass slide using a conventional light microscope in accordance with the reagents' instructions for use. The Pathologists reported the HER2 scores of 0, 1+, 2+ or 3+ for cach of the glass slides examined. The glass slides from each of the two clinical sites respectively were scanned using a different ScanScope® scanner instrument. After a wash-out period of over one (1) week and subsequent randomization of the slides, the same three (3) Pathologists at each clinical site performed a blinded manual read of each digital slide displayed on a computer monitor using the ScanScope XT System's remote viewing capability. The Pathologists reported a HER2 score of 0, 1+, 2+ or 3+ for each of the digital slides corresponding to their respective clinical site.
Statistical analyses are provided for a trichotomous categorization of the HER2 scores combining 0 and 1+ and leaving 2+ and 3+ uncombined. Percentage Agreement (PA) along with an exact 95% Confidence Interval (CI) are presented overall for all trichotomous HER2 score categories combined.
| Pathologist 1 v 2 | Pathologist 1 v 3 | Pathologist 2 v 3 | ||||
|---|---|---|---|---|---|---|
| PA | PA 95% CI | PA | PA 95% CI | PA | PA 95% CI | |
| Clinical site 1 | 91.3% | (82.8, 96.4) | 77.5% | (66.8, 86.1) | 76.3% | (65.4, 85.1) |
| Clinical site 2 | 84.0% | (75.3, 90.6) | 82.0% | (73.1, 89.0) | 90.0% | (82.4, 95.1) |
Manual Microscopy - Inter-Pathologists - Agreements.
| Pathologist 1 v 2 | Pathologist 1 v 3 | Pathologist 2 v 3 | ||||
|---|---|---|---|---|---|---|
| PA | PA 95% CI | PA | PA 95% CI | PA | PA 95% CI | |
| Clinical site 1 | 70.0% | (58.7, 79.7) | 71.3% | (60.0, 80.8) | 71.3% | (60.0, 80.8) |
| Clinical site 2 | 86.0% | (77.6, 92.1) | 79.0% | (69.7, 86.5) | 77.0% | (67.5, 84.8) |
Manual Digital Slide Reading - Inter-Pathologists - Agreements.
| Pathologist 1 | Pathologist 2 | Pathologist 3 | ||||
|---|---|---|---|---|---|---|
| PA | PA 95% CI | PA | PA 95% CI | PA | PA 95% CI | |
| Clinical site 1 | 61.3% | (49.7, 71.9) | 71.3% | (60.0, 80.8) | 92.5% | (84.4, 97.2) |
| Clinical site 2 | 85.0% | (76.5, 91.4) | 84.0% | (75.3, 90.6) | 89.0% | (81.2, 94.4) |
Manual Microscopy vs. Digital Slide Reading - same Pathologist - Agreements.
The percent agreements between the pathologists' manual microscopy and manual read of digital slides ranged from 61.3% to 92.5% with confidence bounds from 49.7% to 97.2%; the inter-pathologists agreements for manual microscopy ranged from 76.3% to 91.3% with confidence bounds from 65.4% to 96.4%.
The inter-pathologists agreements for the manual read of digital slides ranged from 70.0% to 86.0% with confidence bounds from 58.7% to 92.1%; the interpathologists agreements for manual microscopy ranged from 76.3% to 91.3% with confidence bounds from 65.4% to 96.4%.
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Analytical Performance:
a. Precision/Reproducibility:
This precision study was not done on the manual read of the digital slides but using Aperio's IHC HER2 image analysis algorithm. The image analysis algorithm detects and quantifies the same cell features and uses the same scoring scheme as the pathologists reading IHC HER2 slides and was used to quantify objectively the variability of the digital slides provided by the ScanScope systems.
Eight HER2 slides with two slides per HER2 score 0. 1+, 2+ and 3+were sampled from one of the clinical sites to be used in a suite of precision studies. The slides were sampled in sequential order using the rounded average score of the manual microscopy scores provided by the three pathologists.
| Slide | Slide 2 | Slide 3 | Slide 4 | Slide 5 | Slide 6 | Slide 7 | Slide 8 | |
|---|---|---|---|---|---|---|---|---|
| Pathologist | ||||||||
| Pathologist 2 | ||||||||
| Pathologist 3 | ||||||||
| Average | 1 - 2017 - 11 | 11 - 1 - 2 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 | 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. | 1.1.1.1.1. Start 2018 12 12 13.5 1.5 6.6 1.3 1. |
HER2 scores provided by 3 Pathologists for the sampled slides.
Separate studies were conducted to analyze the system introduced variability separately from the variability introduced by the pathologists. Pathologist precision studies werc only performed to be able to put the system variability into perspective to the variability introduced by the pathologists.
System precision studies used the same tumor regions for analysis over all runs to climinate the influence by the pathologists. Pathologist precision studies used the same digital slides to eliminate the influence of the system.
The precision studies analyzed the changes in the system response by extending the analysis of the HER2 score to the underlying cumulative percentages of 3+, 2+ and 1+ cells on which the HER2 score calculations are based. Cumulative percentages of 3+, 2+ and 1+ cells are defined as the percentages of 3+ cells, 3+ and 2+ cells and 3+, 2+ and 1+ cells.
Note that only the accuracy of the HER2 scores was evaluated in the Clinical Comparison to Manual Microscopy.
Intra-System
The eight HER2 slides were scanned 10 times on the same ScanScope system. The image analysis results show perfect agreement (100%) for the calculated HER2 scores and an overall average standard deviation of 0.69% (maximum 2.46%) and average range (maximum – minimum) of 1.22% (maximum 7.14%) for the cumulative percentages of 3+, 2+ and 1+ cells (range from 0.0 to 100.0%) across all runs.
6
Inter-Day/Intra-System
The eight HER2 slides were scanned on the same ScanScope system over 20 times on different days. The image analysis results show perfect agreement (100%) for the calculated HER2 scores and an overall average standard deviation of 0.67% (maximum 2.43%) and average range of 1.68% (maximum 12.07%) for the cumulative percentages of 3+, 2+ and 1+ cells across all runs.
Inter-System
The same eight HER2 slides were scanned 10 times on three different ScanScope systems. The image analysis results show perfect agreement (100%) for the calculated HER2 scores across all systems and all runs. The image analysis results on each of the three ScanScope systems show an overall average standard deviation of 0.69%, 0.59% and 0.57% (maximum 2.46%, 1.65%, 1.34%) and average range of 1.22%, 1,14% and 1.20% (maximum 7.14%, 5.09%, 4.70%) for the cumulative percentages of 3+, 2+ and 1+ cells respectively over all runs. The image analysis results of the three ScanScope systems combined show an overall average standard deviation of 0.78% (maximum 2.41%) and average range of 1.93% (maximum 8.95%) respectively for the cumulative percentages of 3+, 2+ and 1+ cells over all runs.
The following table shows the cumulative percentages of 3+, 2+ and 1+ cells (%) for image analysis of the eight HER2 slides (#S) for the three ScanScope systems.
| S#1 | S#2 | S#3 | S#4 | S#5 | S#6 | S#7 | S#8 | |
|---|---|---|---|---|---|---|---|---|
| 3+ | ||||||||
| % | 3+ | |||||||
| % | 3+ | |||||||
| % | 3+ | |||||||
| % | 3+ | |||||||
| % | 3+ | |||||||
| % | 3+ | |||||||
| % | 3+ | |||||||
| % | ||||||||
| 3+, 2+ | ||||||||
| % | 3+, 2+ | |||||||
| % | 3+, 2+ | |||||||
| % | 3+, 2+ | |||||||
| % | 3+, 2+ | |||||||
| % | 3+, 2+ | |||||||
| % | 3+, 2+ | |||||||
| % | 3+, 2+ | |||||||
| % | ||||||||
| 3+, 2+, 1+ | ||||||||
| % | 3+, 2+, 1+ | |||||||
| % | 3+, 2+, 1+ | |||||||
| % | 3+, 2+, 1+ | |||||||
| % | 3+, 2+, 1+ | |||||||
| % | 3+, 2+, 1+ | |||||||
| % | 3+, 2+, 1+ | |||||||
| % | ||||||||
| ScanScope #1 | 0.0 | 0.0 | 0.0 | 0.1 | 13.7 | 1.7 | 39.5 | 50.5 |
| ScanScope #1 | 0.0 | 0.0 | 0.9 | 1.1 | 58.1 | 50.7 | 73.9 | 51.5 |
| ScanScope #1 | 1.6 | 0.0 | 25.9 | 11.7 | 99.7 | 97.5 | 99.8 | 95.5 |
| ScanScope #2 | 0.0 | 0.0 | 0.0 | 0.0 | 14.0 | 1.6 | 41.5 | 51.3 |
| ScanScope #2 | 0.0 | 0.0 | 0.9 | 1.2 | 60.1 | 51.6 | 74.1 | 51.9 |
| ScanScope #2 | 1.7 | 0.0 | 25.9 | 11.7 | 99.7 | 97.3 | 99.8 | 95.5 |
| ScanScope #3 | 0.0 | 0.0 | 0.0 | 0.1 | ||||
| ScanScope #3 | 0.0 | 0.0 | 0.7 | 1.0 | ||||
| ScanScope #3 | 1.6 | 0.0 | 25.0 | 11.4 |
7
Intra-Pathologist
One pathologist read the same eight HER2 slides 5 times using manual microscopy and 5 times using a manual read of digital slides on a computer monitor. Between reads, the pathologist respected a wash-out period of over four days.
The manual microscopy results show 2 outliers out of 40 scores (5%) and the manual rcad of digital slides results show 3 outliers out of 40 scores (7.5%). Outliers are defined as scores that are different from the median values of the scores provided by the pathologist over 5 runs of the method.
Inter-Pathologists
Three pathologists read the same eight HER2 slides using manual microscopy and using a movel read of digital slides on a computer monitor (used the data from the clinical comparison to manual microscopy study).
The following table shows the HER2 Scores [0, 1, 2, 3] given by the three Pathologists (P1, P2, P3) in the comparison study using manual microscopy for the eight HER2 Slides (S1, S2, ... S8).
| R# | S1 | S2 | S3 | S4 | S5 | S6 | S7 | S8 |
|---|---|---|---|---|---|---|---|---|
| P1 | 0 | 0 | 0 | 1 | 2 | 2 | 3 | 3 |
| P2 | 0 | 0 | 1 | 1 | 2 | 2 | 3 | 3 |
| P3 | 1 | 0 | 1 | 0 | 2 | 2 | 3 | 3 |
| Average | 0 | 0 | 1 | 1 | 2 | 2 | 3 | 3 |
The following table shows the HER2 Scores [0, 1, 2, 3] given by the three Pathologists (P1, P2, P3) in the comparison study using the manual read of the digital slides for the eight HER2 Slides (S1, S2, ... S8).
| R# | S1 | S2 | S3 | S4 | S5 | S6 | S7 | S8 |
|---|---|---|---|---|---|---|---|---|
| P1 | 1 | 0 | 1 | 1 | 3 | 3 | 3 | 3 |
| P2 | 1 | 0 | 1 | 2 | 3 | 3 | 3 | 3 |
| P3 | 1 | 0 | 1 | 0 | 2 | 2 | 3 | 2 |
| Average | 1 | 0 | 1 | 1 | 3 | 3 | 3 | 3 |
The manual microscopy results show 3 outliers out of 24 scores (12.5%) and the manual read of digital slides results show 5 outliers out of 24 scores (21%). Outliers are defined as scores that are different from the median values of the scores provided by the three pathologists in this study.
21 CFR 807.92(b)(3): Conclusions drawn from the nonclinical and clinical tests:
Based on the results of the clinical studies described in this 510(k) submission, it is concluded that the ScanScope System device is as safe and effective (therefore substantially equivalent) as the predicate device as an aid in the assessment of specimens from breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered.
... End of 510(k) Summary ....
8
Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is black and white.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 2 8 2007
Aperio Technologies C/O Perry Johnston 1430 Vantage Court Suite 106 Vista, California 92081
Re: K071671
Trade/Device Name: Scanscope XT System Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry Reagents and Kits Regulatory Class: Class II Product Code: OEO Dated: June 18, 2007 Received: June 19, 2007
Dear Mr. Johnston:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter
9
Page 2 - Aperio Technologies
will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometrics' (OSBs') Division of Postmarket Surveillance at (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Robert Beckerf
Robert L Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
10
Indications for Use
510(k) Number (if known): K071671
Device Name: ScanScope® System
Indications for Use:
The ScanScope® 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 Manual Read of Digital Slides application is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER-2/neu (c-erbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor. HER-2 results are indicated for use as an aid in the management, prognosis and prediction of therapy outcomes of breast cancer.
The IHC HER2 Manual Read of Digital Slides application is intended for use as an accessory to the Dako HercepTest™ to aid the pathologist in the detection and semi-quantitative measurement of HER-2/neu (cerbB-2) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for HER-2 receptors on a computer monitor. 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. Note: The actual correlation of the Dako HercepTest™ to Herceptin® clinical outcome has not been established.
Prescription Use X (21 CFR Part 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Division Sigh-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K071671