The GenASIs ScanView System is an automated scanning microscope and image analysis system. It is intended for in vitro diagnostic use as an aiding tool to the pathologist or cytogeneticist in the detection, classification and enumeration of cells of interest based on color, intensity, size, pattern; and shape. The GenASIs ScanView System is indicated as an accessory to the following FDA cleared/approved devices to detect the following cell types:

CEP® X Spectrum Orange™/CEP® Y Spectrum Green™ DNA Probe Kit and is limited to the analysis of CEP XY probes via high magnification capture and analysis of interphase nuclei. CEP XY is indicated for use to assess the effectiveness of bone marrow transplantation in opposite-sex transplants.
Human breast cancer containing the HER-2/neu gene labeled in Red and the centromere of chromosome 17 labeled in Green via fluorescence in situ hybridization (FISH) in interphase nuclei from formalin-fixed, Paraffin embedded human breast cancer tissue specimens with Vysis® Path Vysion™ HER-2 DNA Probe kit. Results from the PathVysion™ Kit are intended for use as an adjunct to existing clinical and Pathologic information used as prognostic factors in stage II, node-positive breast cancer patients. The Path Vysion™ kit is further indicated as an aid to predict disease-free and overall survival in patients with stage II, node positive breast cancer, treated with adjuvant cyclophosphamide, doxorubicin, and 5fluorouracil (CAF) chemotherapy.
Cells in urine specimens, stained by fluorescence in situ hybridization (FISH) using Vysis UroVysion™ Bladder Cancer Kit to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus. from persons with hematuria suspected of having bladder cancer. The results are intended for use, in conjunction with and not in lieu of current standard diagnostic procedures, as an aid for initial diagnosis of bladder carcinoma in patients with hematuria and subsequent monitoring for tumor recurrence in patients previously diagnosed with bladder cancer.
Gene rearrangements involving the ALK gene (2p23) via fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tissue specimens, using Vysis® ALK (Anaplastic Lymphoma Kinase) Break Apart FISH Probe kit. The Vysis ALK Break Apart FISH Probe Kit is indicated to aid in identifying those patients eligible for treatment with XALKORI® (crizotinib). The GenASIs ALK System is an accessory to Vysis® ALK (Anaplastic Lymphoma Kinase) Break Apart FISH Probe kit.

The GenASIs ScanView System is to be used as an adjunctive automated enumeration tool in conjunction with manual visualization.

Device Description

The GenASIs ScanView System is an integrated digital imaging system constructed of an external microscope, motorized multi slide stage, camera, and a workstation. It is designed to acquire images of cells and enables identification and examination of cells of interest. Experts can view and scan cells and record the image, using both bright field and fluorescent illumination. The acquired images can be enhanced, archived, retrieved and printed. The automated microscope enables Z motion of the slide and the motorized stage enables its X-Y motions. The microscope also includes motorized filter turret containing fluorescence filters.

The system is designed to work with a manual or automated microscope and includes a dedicated, high powered microscope camera combined with state-of-the-art image analysis software for clinical and research oriented image analysis.

The system's modular platform enables automation of a wide range of laboratory selected assays in pathology and cytogenetics applications. This flexible solution may be adapted to the advanced automation and workflow needs of any laboratory or research institution. The system includes a fully automated computer-controlled microscope, motorized 9-slide stage and high powered microscope-camera. This platform also comes with a variety of additional components such as oil dispenser, automated fluorescent illumination control and state-of-the-art image analysis software for clinical and research oriented image analysis and automatic robotic slide loading system, enabling high throughput automated slide analysis for a wide range of pathology applications that provides a true "walk-away" functionality, scanning up to 81 slides consecutively without human intervention. These scanning capabilities presented with the GenASIs High Throughput platform offer an efficient way to optimally use the scanning and analysis system for uninterrupted scanning.

AI/ML Overview

Acceptance Criteria and Device Performance Study for GenASIs ALK System

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Analytical Performance (Method Comparison):
Overall agreement with manual method for positive/negative classification.	100% (95% CI: 98%-100%)
Negative percent agreement with manual method.	100% (95% CI: 97.5%-100%)
Positive percent agreement with manual method.	100% (95% CI: 89.1%-100%)
Precision/Reproducibility (Diagnosis - Positive/Negative):
Within-day/within-system concordance for positive vs. negative results.	100%
Between-days concordance for positive vs. negative results.	100%
Between-systems concordance for positive vs. negative results.	100%
Precision/Reproducibility (Quantitative - Mean % Positive Cells, SD, %CV): For positive specimens, demonstrate acceptable variability in % Positive Cells across different conditions.	Within-day/Within-System: - For manually counted 61%: Mean 56.9, SD 4.6, %CV 8.0 - For manually counted 52%: Mean 46.9, SD 5.9, %CV 12.6 - For manually counted 85%: Mean 79.6, SD 5.2, %CV 6.5 - For manually counted 18%: Mean 22.2, SD 2.9, %CV 13.2 - For manually counted 27%: Mean 26.7, SD 4.2, %CV 15.9 - For manually counted 31%: Mean 29.6, SD 5.7, %CV 19.2Between-Day: - For manually counted 61%: Mean 56.4, SD 3.7, %CV 6.7 - For manually counted 52%: Mean 47.5, SD 4.3, %CV 9.1 - For manually counted 85%: Mean 80.0, SD 3.8, %CV 4.8 - For manually counted 18%: Mean 25.2, SD 4.8, %CV 19.1 - For manually counted 27%: Mean 27.8, SD 3.8, %CV 13.6 - For manually counted 31%: Mean 32.6, SD 6.4, %CV 19.6Between-System: - For manually counted 61%: Mean 56.2, SD 3.1, %CV 5.5 - For manually counted 52%: Mean 46.1, SD 4.4, %CV 9.5 - For manually counted 85%: Mean 79.4, SD 3.5, %CV 4.5 - For manually counted 18%: Mean 24.4, SD 5.0, %CV 20.5 - For manually counted 27%: Mean 28.3, SD 4.1, %CV 14.4 - For manually counted 31%: Mean 32.2, SD 5.9, %CV 18.2Within-day/Within Repeatability for specimens around the cutoff (10-25%):- For manually counted 12%: Mean 11.6, SD 1.62, %CV 13.9- For manually counted 19%: Mean 18.6, SD 1.13, %CV 6.0- For manually counted 22%: Mean 19.7, SD 0.6, %CV 3.1- For manually counted 18%: Mean 17.6, SD 0.98, %CV 5.6- For manually counted 19%: Mean 19.6, SD 1.32, %CV 6.7

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

Sample Size: A total of 179 slides were used in the method comparison study for the test set. This included 9 cases within the equivocal zone (10-50%).
Data Provenance: The slides were archived formalin-fixed paraffin-embedded (FFPE) tissue specimens from patients with non-small cell lung cancer (NSCLC) that had been previously counted and analyzed manually within the last 6 months at four different clinical sites. Negative cases were selected sequentially from a known bank of negative samples. All available positive and equivocal slides during the comparison studies were included. Patients included in the study were negative for the EGFR test.

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

The document states that the ground truth for the test set was established by manual counting results that were performed "in the last 6 months" prior to the study. It does not explicitly state the number of experts used for these manual counts for each individual slide in the test set. However, the study involved four clinical sites, implying that multiple individuals performed these manual counts across the sites. The qualifications of these experts are not explicitly detailed beyond being the standard practice for "manual counting" in a clinical laboratory setting.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for the ground truth. It states that the GenAsIs ScanView operator had "no prior knowledge of the manual counting results." This implies that the manual counts served as the primary, pre-established reference standard against which the device's performance was compared, rather than a process of reaching consensus after the device results were obtained.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. The study compares the device's performance against pre-existing manual counts and assesses the device's own precision and reproducibility. There is no information provided about human readers improving with AI vs. without AI assistance. The GenASIs ALK System is described as an "adjunctive automated enumeration tool in conjunction with manual visualization," suggesting it is intended to assist, but the study design does not directly measure the effectiveness of this human-in-the-loop improvement.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, a standalone performance study was conducted. The "Analytical Performance" section (Table 1) directly compares the GenASIs ScanView results (algorithm only, as the operator had "no prior knowledge of the manual counting results") against the manual method. This demonstrates the algorithm's performance without direct human intervention in the result determination during the comparative phase. The "Precision/Reproducibility" studies also evaluate the device's standalone consistency.

7. Type of Ground Truth Used

The ground truth used was expert consensus / manual counting results performed by laboratory personnel at the clinical sites. These manual counts were established prior to the device's evaluation and served as the reference standard.

8. Sample Size for the Training Set

The document does not provide any information about the sample size used for the training set. It focuses solely on the validation study using the test set.

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

The document does not provide any information on how the ground truth for the training set was established, as details about a training set are not included in this submission summary.

Summary

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Image /page/0/Picture/0 description: The image shows the logo for Applied Spectral Imaging. The logo consists of the letters "ASI" in a stylized font, with the "A" and "S" overlapping. To the right of the letters is a thick, vertical black bar. Below the logo are the words "Applied Spectral Imaging" in a bold font, followed by the tagline "Bringing Details to Light" in a smaller font.

510(k) Summary

As required by section 807.92(c). February 5, 2013

510(K) Number A.

K122554

B. Purpose for Submission

Addition of the GenASIs ALK System Application to the GenASIs ScanView System (former name Scan View System).

The GenASIs ALK System Application is to perform automated fluorescence in situ hvbridization (FISH) detection and enumerationfor the Vysis® ALK (Anaplastic Lymphoma Kinase) Break Apart FISH Probe kit (List No. 06N38-020). The ALK Break Apart FISH Probe is FDA approved (P11012) and is designed to detect rearrangements involving the ALK gene (2p23) via fluorescence in situ hybridization (FISH) in formalinfixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tissue specimens to aid in identifying those patients eligible for treatment with XALKORI® (crizotinib).

Manufacturer and Instrument Name C.

C.1. Device Name

GenASIs ScanView System GenASI ALK System Application

Submitter's name C.2.

Name: Applied Spectral Imaging Ltd. 2 Ha Carmel St, New Industrial Zone, Yokneam 20691, Israel Tel: (972) 4 6547567, Fax: (972) 4 6547507

C.3. Submission contact person

Ilan Sharon P.O.B. 4414 (A-109), Caesarea 30889, Israel TEL: 972-52-8704904

Type of Test or Tests Performed D.

Performing automated fluorescence in situ hybridization (FISH) analysis for samples stained with Vysis ALK Break Apart FISH Probe Kit (List No. 06N38-020) to detect rearrangements involving the ALK gene (2p23) via fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded tissue specimen (FFPE). The test is aimed for analysis of non-small cell lung cancer (NSCLC) tissue specimens, to aid in identifying those patients eligible for treatment with XALKORI® (crizotinib).

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E. System Descriptions

Device description:

F. Regulatory Information

Device Classification

Product Code: NTH 21 CFR 866.4700 CFR section: Immunology Regulation name: . Trade Name: GenASIs ALK System Automated fluorescence in situ hybridization (FISH) Common Name: enumeration system. Class II Classification:

G. Intended Use

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color, intensity, size, pattern; and shape. The GenASIs ScanView System is indicated as an accessory to the following FDA cleared/approved devices to detect the following cell types: 1. CEP® X Spectrum Orange™/CEP® Y Spectrum Green™ DNA Probe Kit and is limited to the analysis of CEP XY probes via high magnification capture and analysis of interphase nuclei. CEP XY is indicated for use to assess the effectiveness of bone marrow transplantation in opposite-sex transplants.

Human breast cancer containing the HER-2/neu gene labeled in Red and the centromere of chromosome 17 labeled in Green via fluorescence in situ hybridization (FISH) in interphase nuclei from formalin-fixed. Paraffin embedded human breast cancer tissue specimens with Vysis® Path Vysion™ HER-2 DNA Probe kit. Results from the Path Vysion " Kit are intended for use as an adjunct to existing clinical and Pathologic information used as prognostic factors in stage II, node-positive breast cancer patients. The Path Vysion™ kit is further indicated as an aid to predict disease-free and overall survival in patients with stage II, node positive breast cancer, treated with adjuvant cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) chemotherapy.
Cells in urine specimens, stained by fluorescence in situ hybridization (FISH) using Vysis UroVysion™ Bladder Cancer Kit to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus, from persons with hematuria suspected of having bladder cancer. The results are intended for use, in conjunction with and not in lieu of current standard diagnostic procedures, as an aid for initial diagnosis of bladder carcinoma in patients with hematuria and subsequent monitoring for tumor recurrence in patients previously diagnosed with bladder cancer.
Gene rearrangements involving the ALK gene (2p23) via fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tissue specimens, using Vysis® ALK (Anaplastic Lymphoma Kinase) Break Apart FISH Probe kit. The Vysis ALK Break Apart FISH Probe Kit is indicated to aid in identifying those patients eligible for treatment with XALKORI® (crizotinib). The GenASIs ALK System is an accessory to Vysis® ALK (Anaplastic Lymphoma Kinase) Break Apart FISH Probe kit.

The GenASIs ScanView System is to be used as an adjunctive automated enumeration tool in conjunction with manual visualization.

Substantial Equivalence Information H.

#	Comparisonparameter	Proposed device:GenASIs ScanView System	Predicate device:ScanView System
1	510(k) number	K122554	K110345
2	Owner	Applied Spectral Imaging Ltd.	Applied Spectral Imaging Ltd.
3	Intended useandindicationsfor use.	The GenASIs ScanView System is anautomated scanning microscope and imageanalysis system. It is intended for in vitrodiagnostic use as an aiding tool to thepathologist or cytogeneticist in thedetection, classification and enumerationof cells of interest based on color.	The ScanView System is an automated scanningmicroscope and image analysis system. It isintended for in vitro diagnostic use as an aidingtool to the pathologist or cytogeneticist in thedetection, classification and enumeration of cellsof interest based on color, intensity, size, pattern;and shape. The ScanView is indicated as anl

1. Comparison of Predicate devices:

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Comparisonparameter	Proposed device:GenASIs ScanView System	Predicate device:ScanView System
	intensity, size, pattern; and shape. TheGenASIs ScanView System is indicated asan accessory to the following FDAcleared/approved devices to detect thefollowing cell types:	accessory to the following FDA cleared/approveddevices to detect the following cell types:
	1. CEP® X Spectrum Orange™/CEP® YSpectrum Green™ DNA Probe Kit and islimited to the analysis of CEP XY probesvia high magnification capture andanalysis of interphase nuclei. CEP XY isindicated for use to assess the effectivenessof bone marrow transplantation in.opposite-sex transplants.	1. CEP® X Spectrum Orange™/CEP® YSpectrum Green™ DNA Probe Kit and is limitedto the analysis of CEP XY probes via highmagnification capture and analysis of inrerphasenuclei. CEP XY is indicated for use to assess theeffectiveness of bone marrow transplantation inopposite-sex transplants.
	2. Human breast cancer containing theHER-2/neu gene labeled in Red and thecentromere of chromosome 17 labeled inGreen via fluorescence in situhybridization (FISH) in interphase nucleifrom formalin-fixed, Paraffin embeddedhuman breast cancer tissue specimens withVysis® Path Vysion™ HER-2 DNA Probekit. Results from the Path Vysion™ Kit areintended for use as an adjunct to existingclinical and Pathologic information used as.prognostic factors in stage II, node-positive breast cancer patients. The PathVysion™ kit is further indicated as an aidto predict disease-free and overall survivalin patients with stage II, node positivebreast cancer, treated with adjuvantcyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) chemotherapy.	2. Human breast cancer containing the HER-2/neu gene labeled in Red and the centromere ofchromosome 17 labeled in Green via fluorescencein situ hybridization (FISH) in interphase nucleifrom formalin-fixed, paraffin embedded humanbreast cancer tissue specimens with Vysis® PathVysion™ HER-2 DNA Probe kit. Results fromthe PathVysionM Kit are intended for use as anadjunct to existing clinical and pathologicinformation used as prognostic factors in stage II,node-positive breast cancer patients. The PathVysionT" kit is further indicated as an aid topredict disease-free and overall survival inpatients with stage II, node positive breast cancer,treated with adjuvant cyclophosphamide,doxorubicin, and 5- fluorouracil (CAF)chemotherapy.
	3. Cells in urine specimens, stained byfluorescence in situ hybridization (FISH)using Vysis UroVysion™ Bladder CancerKit to detect aneuploidy for chromosomes3, 7, 17, and loss of the 9p21 locus, frompersons with hematuria suspected ofhaving bladder cancer. The results areintended for use, in conjunction with andnot in lieu of current standard diagnosticprocedures, as an aid for initial diagnosisof bladder carcinoma in patients withhematuria and subsequent monitoring fortumor recurrence in patients previouslydiagnosed with bladder cancer.	3. Cells in urine specimens, stained byfluorescence in situ hybridization (FISH) usingVysis UroVysion™ Bladder Cancer Kit to detectaneuploidy for chromosomes 3, 7, 17, and loss ofthe 9p21.locus, from persons with hemnaturiasuspected of having bladder cancer. The resultsare intended for use, in conjunction with and notin licu of current standard diagnostic procedures,as an aid for initial diagnosis of bladdercarcinoma in patients with hemnaturia andsubsequent monitoring for tumor recurrence inpatients previously diagnosed with bladdercancer.
		paraffin-embedded (FFPE) non-small celllung cancer (NSCLC) tissue specimens, .	4. Gene rearrangements involving theALK gene (2p23) via fluorescence in situhybridization (FISH) in formalin-fixed	The ScanView System is to be used as anadjunctive automated enumeration tool inconjunction with manual visualization.
using Vysis® ALK (Anaplastic

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#	Comparisonparameter	Proposed device:GenASIs ScanView System	Predicate device:ScanView System
		Lymphoma Kinase) Break Apart FISHProbe kit. The Vysis ALK Break ApartFISH Probe Kit is indicated to aid inidentifying those patients eligible fortreatment with XALKORI® (crizotinib).The GenASIs ALK System is an accessoryto Vysis® ALK (Anaplastic LymphomaKinase) Break Apart FISH Probe kit.
		The GenASIs ScanView System is to beused as an adjunctive automatedenumeration tool in conjunction withmanual visualization.
4	Probe Kit(for GenASIsALK System)	Vysis® ALK Break Apart FISH Probe Kit(List No. 06N38-020).	Vysis UroVysionTM Bladder Cancer Kit
5	TechnicalMethod	Fluorescence in situ hybridization FISH,an adjunctive automated enumeration toolin conjunction with manual visualization.	Fluorescence in situ hybridization FISH, anadjunctive automated enumeration tool inconjunction with manual visualization.
6	Target Area(for GenASIsALK System)	Formalin-fixed, paraffin-embedded humannon-small cell lung cancer tissue specimen	Cells in urine specimens
7	ImageSpecialResolution	1280 X 1024 pixels	1280 X 1024 pixels
8	DeviceComponents	Automated microscope,PC, keyboard andcontrol panel, colormonitor, CCD Camera,and motorized stage	Automated microscope,PC, keyboard andcontrol panel, colormonitor, CCD Camera,and motorized stage
9	SoftwareVersion	GenASIs ScanView Version 7.0	ScanView Version 6.0
10	SoftwareApplications	• Control of man-machineInterface.• Scan, Capture, Reviewand images analysis• Handling the images display, storage andcommunication.	• Control of man-machineInterface.• Scan, Capture, Reviewand images analysis• Handling the images display, storage andcommunication.

2. Substantial Equivalence discussion

Similarities:

Both the proposed GenASIs ScanView system and legally cleared ScanView System (K110345) are platforms for IVD medical devices and laboratory test systems. Both systems use automated scanning microscope, CCD camera, image analysis software tools, storage media and display monitor as an aiding tool to the pathologist or cytogeneticist, in the detection, classification and enumeration of cells of interest based on color, intensity, size, pattern and shape.

The proposed GenASIs ScanView system and legally cleared ScanView System (K110345) predicate device are both adjunctive automated enumeration tools for FISH.

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Differencés:

The legally cleared Scan View System (K110345) is using software version 6.0 while proposed GenASIs ScanView system is using software version 7.0 that includes same applications and tools but has improved features, corrected bugs and is using improved SQL data base for storage (CDM). Additionally the proposed device includes ALK flow capability implemented by using the same FISH and spot counting tools. The legally cleared ScanView System is for use with Vysis UroVysion™ Bladder Cancer Kit, the proposed GenASIs ScanView system is additionally indicated for using Abbott's FDA approved (P110012) Vysis ALK Break Apart FISH Probe Kit (Vysis ALK Break Apart FISH Probe Kit (List No. 06N38-020)) to detect rearrangements involving the ALK gene (2p23) via fluorescence in situ hybridization (FISH) in formalin-fixed paraffinembedded (FFPE) non-small cell lung cancer (NSCLC) tissue specimens, to aid in identifying those patients eligible for treatment with XALKORI® (crizotinib).

I. Special Control/ Guidance Document Referenced (if applicable)

The following Special Control and guidance documents are used in the preparation of the 510(K) submission:

"Class II Special Controls Guidance Document: Automated Fluorescence in situ Hybridization (FISH) Enumeration Systems" 23 May 2005.
Guidance for Industry and FDA Staff: "Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests"; March 2007.
"Guidance for the Content of Premarket Submission for Software Contained in Medical Device", CDRH, May 2005.

J. Performance Characteristics

The following information of the device performance characteristics are based on ASI testing and experiments, using the Vysis® ALK™ FISH probe kit. The operators should be aware of the limitations derived from the following performance characteristics:

a. Analytical Performance:

Slides containing formalin-fixed paraffin-embedded (FFPE) tissue specimens from patients with non-small cell lung cancer (NSCLC) were hybridized with the FDA approved Vysis ALK Break Apart FISH Probe Kit according to the manufacturer's instructions.

At each clinical site, archived slides from NSCLC tissue specimens, previously counted and analyzed manually in the last 6 months, were used for the test. Negative cases were selected sequentially from a known bank of negative samples. All positive and equivocal slides that were available during the period of the comparison studies were used for the analysis in

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order to have an adequate number of slides in each of the categories.

Patients with NSCLC that were negative for the EGFR test were included in the study. At four clinical sites, a total of 179 slides including 9 cases in the equivocal zone (10-50%) were analyzed. The GenASIs Scan View operator had no prior knowledge of the manual counting results. Method comparison results for all four sites combined are presented below in Table 1:

Table 1: Method Comparison of GenASIs ScanView vs. Manual Method – All sites combined

			Manual Method
		Negative	Positive	Total
GenASIs	Negative	ব		147
Scan View	Positive
Method	l otal		c	179

Overall agreement: 100%% (95% CI: 98%-100%) Negative percent agreement: 100% (95% CI: 97.5%-100%) Positive percent agreement: 100% (95% CI: 89.1%-100%)

b. Precision/Reproducibility:

A panel of 10 slides chosen by the manual counting results, 4 of which were negative (<10%), 3 equivocal (10-50%) and 6 positive (>50%) were evaluated for repeatability and reproducibility of diagnosis (positive/negative) for the following:

· Within-day/within system: each one of the slides was evaluated three times on the same system on the same day.
· Between days: slides were assessed on three separate days on the same system (interval between assessments was at least five days).
· Between systems: three GenASIs ScanView ALK Systems were used at three different sites by three different operators.

Diagnoses over different days and systems were 100% concordant for positive vs. negative results, as were within-day results. Both repeatability and reproducibility in the study were 100%.

Mean percent positive cells, standard deviation and % coefficient of variation for each study are presented in Table 2 below. For the negative specimens %CV values are not applicable as a higher degree of variance is to be expected in negative or low positive specimens due to the fewer signals.

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PanelMember	%PositiveCellsCountedManually	Within-day/Within-System			Between-Day			Between-System
		Mean %PositiveCells	SD	%CV	Mean %PositiveCells	SD	%CV	Mean %PositiveCells	SD	%CV
1	61	56.9	4.6	8.0	56.4	3.7	6.7	56.2	3.1	5.5
2	52	46.9	5.9	12.6	47.5	4.3	9.1	46.1	4.4	9.5
3	85	79.6	5.2	6.5	80.0	3.8	4.8	79.4	3.5	4.5
4	0	0.9	1.0	N/A	1.2	0.8	N/A	1.1	0.7	N/A
5	0	1.3	1.3	N/A	0.8	1.1	N/A	1.1	1.1	N/A
6	0	0.6	0.7	N/A	0.5	0.5	N/A	0.7	0.7	N/A
7	0	0.6	1.0	N/A	0.9	0.8	N/A	0.8	0.8	N/A
8	18	22.2	2.9	13.2	25.2	4.8	19.1	24.4	5.0	20.5
9	27	26.7	4.2	15.9	27.8	3.8	13.6	28.3	4.1	14.4
10	31	29.6	5.7	19.2	32.6	6.4	19.6	32.2	5.9	18.2

Table 2: Repeatability and reproducibility analysis by panel member

An additional panel of 5 equivocal specimens around the cutoff (10-25%) were tested for repeatability within-day/within-system. Results are presented in Table 3 below:

Panel Member	% Positive CellsCounted Manually	Mean%Positive Cells	SD	%CV
1	12	11.6	1.62	13.9
2	19	18.6	1.13	6.0
3	22	19.7	0.6	3.1
4	18	17.6	0.98	5.6
5	19	19.6	1.32	6.7

Table 3: Within-day/Within Repeatability for specimens around the cutoff

c. Linearity

Not applicable

d. Carryover:

Not applicable

e. Interfering Substances:

Not applicable

3. Other Supportive Instrument Performance Data Not Covered Above:

Not applicable

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K. Proposed Labeling

Labeling was prepared in accordance with the requirements of 21 CFR Part 809.10.

Conclusion L.

Based on the above, it is Applied Spectral Imaging's opinion that the proposed GenASIs System is substantially equivalent in terms of design, principles, and performance characteristics and is shown to be safe & effective for its intended use.

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Image /page/9/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is an emblem of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 7, 2013

Applied Spectral Imaging Ltd. Ilan Sharon P.O.B. 4414 (A-109) Caesarea 30889, Israel

Re: K122554

Trade/Device Name: GenASIs ScanView System, GenASI ALK System Regulation Number: 21 CFR 866.4700 Regulation Name: Automated fluorescence in situ hybridization (FISH) enumeration systems . Regulatory Class: Class II Product Code: NTH Dated: February 6, 2013 Received: February 7, 2013

Dear Mr. Sharon:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you; however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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

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Page 2 - Ilan Sharon

comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807): labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go.to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Reena Pihilips-S

for

Maria M. Chan, Ph.D.

Director

Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health

Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K122554

Device Name: GenASIs ScanView System

Indications for Use:

CEP® X Spectrum Orange™/CEP® Y Spectrum Green™ DNA Probe Kit and is limited to the analysis of CEP XY probes via high magnification capture and analysis of interphase nuclei. CEP XY is indicated for use to assess the effectiveness of bone marrow transplantation in opposite-sex transplants.
Human breast cancer containing the HER-2/neu gene labeled in Red and the centromere of chromosome 17 labeled in Green via fluorescence in situ hybridization (FISH) in interphase nuclei from formalin-fixed, Paraffin embedded human breast cancer tissue specimens with Vysis® Path Vysion™ HER-2 DNA Probe kit. Results from the PathVysion™ Kit are intended for use as an adjunct to existing clinical and Pathologic information used as prognostic factors in stage II, node-positive breast cancer patients. The Path Vysion™ kit is further indicated as an aid to predict disease-free and overall survival in patients with stage II, node positive breast cancer, treated with adjuvant cyclophosphamide, doxorubicin, and 5fluorouracil (CAF) chemotherapy.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Reena Philip

Division Sign-Off

Office of In Vitro Diagnostics and Radiological Health

510(k) K122554

Page 1 of 2

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Indications for Use

510(k) Number (if known): K122554

Device Name: GenASIs ScanView System

Indications for Use: Continued from last page.

Cells in urine specimens, stained by fluorescence in situ hybridization (FISH) using Vysis UroVysion™ Bladder Cancer Kit to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus. from persons with hematuria suspected of having bladder cancer. The results are intended for use, in conjunction with and not in lieu of current standard diagnostic procedures, as an aid for initial diagnosis of bladder carcinoma in patients with hematuria and subsequent monitoring for tumor recurrence in patients previously diagnosed with bladder cancer.
Gene rearrangements involving the ALK gene (2p23) via fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tissue specimens, using Vysis® ALK (Anaplastic Lymphoma Kinase) Break Apart FISH Probe kit. The Vysis ALK Break Apart FISH Probe Kit is indicated to aid in identifying those patients eligible for treatment with XALKORI® (crizotinib). The GenASIs ALK System is an accessory to Vysis® ALK (Anaplastic Lymphoma Kinase) Break Apart FISH Probe kit.

The GenASIs ScanView System is to be used as an adjunctive automated enumeration tool in conjunction with manual visualization.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Reina Philip

Division Sign-Off

Office of In Vitro Diagnostics and Radiological Health

510(k) K122554

Page 2 of 2

Regulation Number and Section

§ 866.4700 Automated fluorescence

in situ hybridization (FISH) enumeration systems.(a)
Identification. An automated FISH enumeration system is a device that consists of an automated scanning microscope, image analysis system, and customized software applications for FISH assays. This device is intended for in vitro diagnostic use with FISH assays as an aid in the detection, counting and classification of cells based on recognition of cellular color, size, and shape, and in the detection and enumeration of FISH signals in interphase nuclei of formalin-fixed, paraffin-embedded human tissue specimens.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Automated Fluorescencein situ Hybridization (FISH) Enumeration Systems.” See § 866.1(e) for the availability of this guidance document.