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 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.

Device Description

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.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve X% agreement"). Instead, it focuses on demonstrating "substantial equivalence" through agreement percentages within and between pathologists and methods. The performance is presented as ranges and specific percentages.

Acceptance Criteria (Implied)	Reported Device Performance
Clinical Comparison: Agreement between manual microscopy and manual digital slide reading (same pathologist)	Range from 61.3% to 92.5% with 95% CI from 49.7% to 97.2%.
Clinical Comparison: Inter-Pathologist Agreement (Manual Microscopy)	Range from 76.3% to 91.3% with 95% CI from 65.4% to 96.4%.
Clinical Comparison: Inter-Pathologist Agreement (Manual Digital Slide Reading)	Range from 70.0% to 86.0% with 95% CI from 58.7% to 92.1%.
Analytical Performance (Intra-System Precision) - Calculated HER2 scores	100% agreement.
Analytical Performance (Intra-System Precision) - Cumulative percentages of 3+, 2+ and 1+ cells	Overall average standard deviation of 0.69% (max 2.46%) and average range of 1.22% (max 7.14%).
Analytical Performance (Inter-Day/Intra-System Precision) - Calculated HER2 scores	100% agreement.
Analytical Performance (Inter-Day/Intra-System Precision) - Cumulative percentages of 3+, 2+ and 1+ cells	Overall average standard deviation of 0.67% (max 2.43%) and average range of 1.68% (max 12.07%).
Analytical Performance (Inter-System Precision) - Calculated HER2 scores	100% agreement across all systems and all runs.
Analytical Performance (Inter-System Precision) - Cumulative percentages of 3+, 2+ and 1+ cells	Overall average standard deviation of 0.78% (max 2.41%) and average range of 1.93% (max 8.95%) when combining results from three ScanScope systems. Individual system st. dev. ranged from 0.57% to 0.69% and average range from 1.14% to 1.22%.
Analytical Performance (Intra-Pathologist Precision) - Manual Microscopy Outliers	2 outliers out of 40 scores (5%).
Analytical Performance (Intra-Pathologist Precision) - Manual Digital Slide Reading Outliers	3 outliers out of 40 scores (7.5%).
Analytical Performance (Inter-Pathologist Precision) - Manual Microscopy Outliers	3 outliers out of 24 scores (12.5%).
Analytical Performance (Inter-Pathologist Precision) - Manual Digital Slide Reading Outliers	5 outliers out of 24 scores (21%).

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size:
- Clinical Comparison Study: 180 formalin-fixed, paraffin-embedded breast tissue specimens.
- Precision/Reproducibility Study: 8 HER2 slides (with two slides per HER2 score 0, 1+, 2+, and 3+).
Data Provenance:
- Clinical Comparison Study: 80 specimens from a "first clinical site" and 100 specimens from a "second clinical site." The text does not specify the country of origin, but it implies a clinical setting within the US given the FDA submission. The study was prospective in the sense that the readings were done as part of the study, rather than re-analyzing existing interpretations. The specimens themselves might have been collected retrospectively from existing tissue banks.
- Precision/Reproducibility Study: The 8 HER2 slides were "sampled from one of the clinical sites." Similar to the above, the country of origin is not explicitly stated but implied to be within the US.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Clinical Comparison Study: Three (3) pathologists at each of the two clinical sites were used, totaling six pathologists for the study (3 per site). The qualifications are stated as "Pathologists," which implies they are medical doctors specialized in pathology. No specific experience level (e.g., 10 years) is given.
Precision/Reproducibility Study (for initial slide sampling): The "rounded average score of the manual microscopy scores provided by the three pathologists" was used to sample the 8 slides.
Precision/Reproducibility Study (Intra-Pathologist): One pathologist.
Precision/Reproducibility Study (Inter-Pathologists): Three pathologists.

4. Adjudication Method for the Test Set

The primary clinical comparison study used a "blinded manual examination" by individual pathologists. The agreement percentages are reported between pathologists and between methods (manual microscopy vs. digital reading for the same pathologist). There is no explicit mention of an adjudication method (like 2+1 or 3+1) to establish a single, definitive ground truth for each case by consensus or a senior expert for the entire test set. Instead, the study design allows for comparing agreement rates.

For the precision studies, "outliers are defined as scores that are different from the median values of the scores provided by the pathologist over 5 runs" (Intra-Pathologist) or "scores that are different from the median values of the scores provided by the three pathologists in this study" (Inter-Pathologist). This is a method for identifying discrepancies, not necessarily for adjudicating a final ground truth for each case for the purpose of primary performance metrics.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

Was an MRMC study done? Yes, a form of MRMC study was performed in the "Comparison studies: a. Method comparison with predicate device." It involved multiple readers (pathologists) and multiple cases (180 specimens). It compared two reading methods: manual microscopy and manual digital slide reading.
Effect Size of AI assistance: The device (ScanScope XT System) is described as an "automated digital slide creation, management, viewing and analysis system." However, the "IHC HER2 Manual Read of Digital Slides application" specifically tested in the clinical comparison is for manual examination of digital slides by a pathologist. The document explicitly states: "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 ... by manual examination of the digital slide...".

Therefore, this study does not measure the effect size of AI assistance on human readers. It rather evaluates the equivalence of reading digital slides on a monitor to reading physical slides under a microscope.

While there is a mention of "Aperio's IHC HER2 image analysis algorithm" within the precision/reproducibility section, that part of the study was not for clinical comparison or human reader improvement, but to objectively quantify system variability separate from pathologist variability. The clinical comparison specifically focuses on the manual read function of the digital slides by pathologists.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, a standalone performance assessment was conducted for the device's analytical capabilities in terms of image analysis on HER2 scores. This specifically evaluated "Aperio's IHC HER2 image analysis algorithm" (not the manual reading by pathologists). The precision studies (Intra-System, Inter-Day/Intra-System, Inter-System) were done using this algorithm, with results showing 100% agreement for calculated HER2 scores and very low standard deviations/ranges for cellular percentages. This demonstrates the performance of the algorithm without human intervention for specific analytical tasks, separate from the clinical "manual read" study.

7. The Type of Ground Truth Used

Clinical Comparison Study (for the comparison itself): The ground truth for the comparison was essentially established by the pathologists' manual microscopic examination of the glass slides. The digital readings were compared against this traditional method, which serves as the established clinical standard. There isn't an "absolute" or "independent" ground truth like pathology reports from excisional biopsies or patient outcomes explicitly stated for each case in the comparison data. The predicate device for substantial equivalence also relies on manual microscopic assessment.
Precision/Reproducibility Study (for sampling): The 8 slides used for precision studies were sampled based on the "rounded average score of the manual microscopy scores provided by the three pathologists," implying a consensus-based approach derived from expert readings.

8. The Sample Size for the Training Set

The document does not explicitly state a sample size for a "training set." The clinical study described is a comparison study and precision study, not a study for training or validating an AI model for clinical decision-making with direct human-in-the-loop assistance. While the text mentions "Aperio's IHC HER2 image analysis algorithm," it doesn't provide details on how this algorithm was trained or validated.

9. How the Ground Truth for the Training Set Was Established

Since no specific training set and its ground truth establishment are detailed for an AI model for clinical use in this submission, this information is not available in the provided text. The "ground truth" referenced for the analytical precision studies of the algorithm is inherent in its design to quantify cell features and use a scoring scheme mimicking pathologists' manual approaches.

Summary

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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, operatorintervention)

510k Summary – 510k-2 - Rev26Nov2007 – final

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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 HER2software 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

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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 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

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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).

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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 5	Slide 7
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.

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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

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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	S3	S4	S5	S6	S7	S8
P1	0	0	1	2	2	3	3
P2	0	1	1	2	2	3	3
P3	1	1	0	2	2	3	3
Average	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	S3	S4	S5	S6	S7	S8
P1	1	1	1	3	3	3	3
P2	1	1	2	3	3	3	3
P3	1	1	0	2	2	3	2
Average	1	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 ....

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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

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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

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Indications for Use

510(k) Number (if known): K071671

Device Name: ScanScope® System

Indications for Use:

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.

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

Regulation Number and Section

§ 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.