MODIFICATION TO DUET SYSTEM

K050840 · Bioview , Ltd. · JOY · Aug 16, 2005 · Hematology

Device Facts

• Record ID: K050840
• Device Name: MODIFICATION TO DUET SYSTEM
• Applicant: Bioview , Ltd.
• Product Code: JOY · Hematology
• Decision Date: Aug 16, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5260
• Device Class: Class 2

Intended Use

The Duet™ 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 in the detection, classification and counting of cells of interest based on color, intensity, size, pattern, and shape. The Duet™ System is intended to detect: 1. Hematopoietic cells stained by Giemsa stain, Immunohistochemistry or ISH (with bright field and fluorescent) prepared from cell suspension. 2. Amniotic cells stained by FISH (using direct labeled DNA probes for chromosomes X, Y, 13, 18 and 21). 3. Cells in urine specimens, stained by FISH (using the Vysis UroVysion™ Bladder Cancer Recurrence Kit for chromosomes 3, 7, 17 and 9p21 locus), from subjects with transitional cell carcinoma of the bladder.

Device Story

Duet™ System is an automated scanning microscope and image analysis platform; automates slide screening; reduces time/labor. Inputs: cell samples on slides (bright field or fluorescent illumination). Operation: scans slides; captures images; classifies cells based on morphology, staining (Giemsa, IHC), and fluorescent signals. Output: gallery of captured targets; summary report. Used in laboratory settings; operated by pathologists/technicians. Workflow: user enters scan parameters; system performs automated scan; user reviews results, corrects classifications, and generates reports. Benefits: assists pathologist in detection/enumeration of cells; improves efficiency compared to manual microscopy.

Clinical Evidence

Bench testing only. Study 1: Comparison of Duet™ vs. manual scoring on 135-178 slides using Vysis UroVysion™ Kit. Results showed high correlation; Kappa agreement index 0.918 (p<0.0001); 96.2% agreement for FISH positive and 95.7% for FISH negative. Study 2: Reproducibility/repeatability study on 4 slides across 3 systems; 100% intra-system agreement and 91.7% inter-system agreement; 95.0% overall agreement.

Technological Characteristics

Automated scanning microscope and image analysis system. Supports bright field and fluorescent illumination. Connectivity: standalone. Standards: EN 61010-1, EN 61326-1, IEC 60601-1-4, EN-1441, ISO 14971. Software: automated image analysis for cell classification based on color, intensity, size, pattern, and shape.

Indications for Use

Indicated for use as an aiding tool to pathologists for detection, classification, and counting of cells in hematopoietic cell suspensions (Giemsa, IHC, ISH), amniotic cells (FISH for chromosomes X, Y, 13, 18, 21), and urine specimens from patients with transitional cell carcinoma of the bladder (FISH for chromosomes 3, 7, 17, 9p21).

Regulatory Classification

Identification

An automated cell-locating device is a device used to locate blood cells on a peripheral blood smear, allowing the operator to identify and classify each cell according to type. (Peripheral blood is blood circulating in one of the body's extremities, such as the arm.)

Predicate Devices

• Duet™ System (K030192, K040591)
• Vysis UroVysion™ Bladder Cancer Recurrence Kit (K011031, K033982)
• Vysis AutoVysion™ System (K041875)

Submission Summary (Full Text)

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# 510(K) SUMMARY

Duet™ system

# 510(k) Number K_050840

# Applicant's Name:

Bioview Ltd. 3 Pekeris St. Rehovot P.O.B. 4051, Nes Ziona 70400, Israel Tel: [phone] Fax: [phone]

#### Contact Person:

Dorit Winitz, Ph.D. Biomedical Strategy Ltd. 11 Menachem Begin Street. Ramat Gan 52521, Israel Tel: [phone] Fax: [phone] Mail: [e-mail]

#### Date Prepared:

March, 2005

#### Trade Name:

Duet™ System

# Classification Name:

Automated cell-location device and: Automated Fluorescence in situ Hybridization (FISH) Enumeration Systems

# Classification:

FDA has classified Automated cell-locating devices (product code JOY, I'DA Tias Chassillor No. 864.5260) and Automated Fluorescence In situ Hybridization

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(FISH) Enumeration Systems (product code NTH, Regulation No. 866.4700) as class II devices and they are reviewed by the Pathology and Immunology Panels, respectively.

#### Predicate Devices:

- · Duet™ System, cleared under K030192, and K040591 (Product code JOY)
- · Vysis UroVysion™ Bladder Cancer Recurrence Kit, cleared under K011031 and K033982 (Product code NOT)
- · Human manual visualization of urine specimens cells from subjects with transitional cell carcinoma of the bladder, probed by the UroVysion™ Kit by conventional microscope.
- · Vysis@ AutoVysion™ System, K041875 (product code NTH)

# Performance Standards:

No performance standards have been established for such device under Section 514 of the Federal Food, Drug, and Cosmetic Act. However, the Duet™ system complies with the following voluntary standards:

- . EN 61010-1
- # EN 61326-1
- IEC 60601-1-4 용
- EN-1441: Medical devices Risk Analysis. す
- ISO 14971 Medical Devices-Risk Management .

#### Indications:

The Duet™ 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 in the detection, classification and counting of cells of interest based on color, intensity, size, pattern, and shape. The Duet™ System is intended to detect:

- 1. Hematopoietic cells stained by Giemsa stain, Immunohistochemistry or ISH (with bright field and fluorescent) prepared from cell suspension.
- 2. Amniotic cells stained by FISH (using direct labelcd DNA probes for chromosomes X, Y, 13, 18 and 21).
- 3. Cells in urine specimens, stained by FISH (using the Vysis UroVysion™ Bladder Cancer Recurrence Kit for chromosomes 3, 7, 17 and 9p21 locus), from subjects with transitional cell carcinoma of the bladder.

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#### Device Description:

The Duet™ System is a fully integrated imaging and scanning platform that automates time-consuming and difficult laboratory tasks of slide screening by making a significant reduction in time and labor currently required.

The Duet™ scans in high resolution and in full color cell samples at high speed both in bright light illumination and in fluorescent illumination.

Duet™ suggests classification of the cells according to their morphological features, their staining (Giemsa, IHC) and fluorescent signals, and allows the user to quickly examine the results, correct them as needed and generate a report summarizing the sample's data. The unique feature of the Duet system allows the presents combined presentation of morphological and specific staining information of the same cell, for all the cells of the sample.

# Substantial Equivalence:

#### Intended use

The intended use of the Duet™ System is expanded to include the indication of an aiding tool in the detection of aneuploidy for chromosomes 3, 7, 17 and loss of the 9p21 locus via FISH in Urine specimens from subjects with transitional cell carcinoma of the bladder, probed by the Vysis UroVysion™ Bladder Cancer Recurrence Kit

Detection, classification and counting of urine specimens from subjects with traditional cell carcinoma of the bladder, stained using the cleared Vysis UroVysion™ Bladder Cancer Recurrence Kit are routinely performed manually by cytogeneticist using conventional microscopes, according to the kit instructions.

The claim of an automated aiding tool for detection and enumeration of FISH signals is also claimed by the 510(k)-cleared Vysis AutoVysion™ System and the previously cleared Duet™ System.

The Duet™ System employs the same procedures as employed by human manual visualization using conventional microscopes. Additionally, the new intended use was supported by a comparative performance study demonstrating that the operation of the Duet™ System is safe and effective as an aiding tool in the detection of aneuploidy for chromosomes 3, 7, 17 and loss of the 9p21 locus via FISH in urine specimens from subjects with transitional cell carcinoma of the bladder, probed by the Vysis UroVysion™ Bladder Cancer Recurrence Kit, in comparison to manual microscopy.

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# Technological characteristics

The current Duet™ System is the same system as the 510(k)-cleared Duet™ System. No changes were incorporated to the system's hardware or software to support the new indication.

# Mode of Operation

Exactely as the cleared Duet™ System, the current Duet™ System provides two modes of operation:

- · Automatic scanning: provides a gallery of targets that the system captures for all identified cells.
- Manual scanning: provides interactive control over the microscope. . This enables a user-controlled scan of any slide under either bright field or fluorescent illumination.

The user of the current Duet™ Systems, enters the scan parameters, slide number, comments, and annotates the results in the same manner as done using the predicate devices and during standard human visualization of cytology slides. Similarly, final classification is performed by the operator.

A special task was designed for the use of the Duet™ System with the UroVysion™ Kit, defining filters, classes and stop criteria in accordance with the UroVysion™ Kit. In addition, specific instructions for scanning and analysis of the UroVysion™ Kit were added to the Duet™ User's manual. The performance studies described below confirms that any minor differences between the manual and the automated Duet™ System do not raise any issue of safety or efficacy.

# Performance characteristics of the Duet System:

Performance characteristics of the Duet System were verified by the following studies:

#### 내 Study 1 - Comparison of the Duet™ System method to manual scoring method

This study was performed to demonstrate the equivalency of the Duet™ method to the manual scoring method for detection and enumeration of slides probed by the Vysis Urovysion™ Bladder Cancer Recurrence Kit.

Total of 135 slides were probed using the Vysis UroVysion™ Bladder Cancer Recurrence Kit according to the manufacturer instructions (Vysis Inc., Downers Grove, IL). The slides were screened both manually and using the Duet™ system, while the slides at one of the laboratories were screened

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twice for each method. Statistical analysis was performed for each study separately and for the pooled results (178 slides).

The statistical analysis performed included acceptable accuracy analysis with calculation of positive/negative predictive values, combined with Kappa value for agreement level.

High correlation was found between the results of the manual method and the Duet™ Method, showing excellent accuracy in detecting both normal and abnormal samples, as defined by the manual method. The overall agreement level between both methods (described by Kappa agreement level index) was calculated to be 0.918 (P-value<0.0001), with 96.2% agreement in observing "FISH Positive" and 95.7% in observing "FISH negative". No significant differences were found between results from different sites.

The comparison between the Duet™ method and the manual microscopy method demonstrated that the Duet™ system is effective and suitable for distinguishing between FISH negative and FISH positive urine specimens from subjects with transitional cell carcinoma of the bladder, probed by the Vysis UroVysion Bladder Cancer recurrence Kit.

#### Study 2 - Evaluation the performance of the Duet™ System in 트 terms of reproducibility and repeatability, within a system and across systems.

The reproducibility and repeatability analysis was performed to evaluate the precision of the Duet™ System in the detection and enumeration of transitional cell carcinoma of the bladder, probed by the Vysis UroVysion Bladder Cancer recurrence Kit.

The experiment included four (4) slides, such that each slide was analyzed on three (3) different systems and three (3) times on one of these systems. The slides were selected to cover the range of the intended use, namely, to include two (2) negative slides, one (1) positive and one (1) near the medical decision cutoff. The experiment was performed by two (2) operators at Bio View Lab, in cooperation with Meir Hospital, Kfar Saba, Israel.

System reliability, measured by its consistency, in terms of reproducibility and repeatability, was demonstrated by calculating the percentage of agreement between measurements. A high, value indicates a small variance between different runs on the same machine, relative to the differences between machines. The calculated results of the variance within the measurements using the same Duet™ system revealed 100% agreement (12 out of 12), while 91.7% (11 out of 12) agreement between systems was revealed. The overall agreement level was found to be 95.0%. Therefore it

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can be concluded that the Duet™ System had proven to have high values of both repeatability and reproducibility.

# Conclusion:

Bioview Ltd. believes that the Duet™ System is substantially equivalent to the combination of its predicate devices in terms of Intended Use, Indications for Use, technological characteristics and mode of operation. Any minor differences between the Duet™ System and its predicate devices do not raise new safety or effectiveness issues, based on the performance results and the analysis of similarities and differences presented above.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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AUG 1 6 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Bioview Ltd. c/o Dorit Winitz, Ph.D. Biomedical Strategy Ltd. 11 Menachem Begin Street Ramat Gan, 52521 Israel

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k050840 Re:

Trade/Device Name: Duet™ system Regulation Number: 21 CFR 864.5260 Regulation Name: Automated cell-locating device Regulatory Class: Class II Product Code: JOY Dated: March 28, 2005 Received: April 13, 2005

Dear Dr. Winitz:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your bection 910(t) fee device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the encreativent of the enactment date of the Medical Device Amendments, or 10 conninered pror to May 20, 1978, in ecordance with the provisions of the Federal Food, Drug, de rices that have been require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, morelore, mains of the Act include requirements for annual registration, listing of general controls pro rise ring 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), if your doviee is classified al controls. Existing major regulations affecting your device it indy be subject to back as 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 1 teast be advised that 1 1971 brissian that your device complies with other requirements of the Act that I Dr. Has intact a and regulations administered by other Federal agencies. You must or any 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). requirements as bet form in the in marketing your device as described in your Section 510(k) rms icter will anon your to ought finding of substantial equivalence of your device to a legally premative notification ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' device to proceed to the market.

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Page 2 -

If you desire specific information about the application of labeling requirements to your device, If you destro specific infortion and advertising of your device, please contact the Office of In of quostions on the promie Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CER Part 807.97). Tou may obtain other general information on your responsibilities under the Act from the rou may outlif only. Beller generational and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

lobatz Beckeyh

Robert L. Becker, Jr., MD, Pa 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

Koso Sup 510(k) Number (if known):

Device Name:

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Indications for Use: The Duet™ System is an automated scanning microscope and image analysis system. It is intended for in-vitro diagnostic usc as an aiding tool to the pathologist in the detection, classification and counting of cells of interest based on color, intensity, size, pattern, and shape. The Duet™ System is intended to detect:

- by Giemsa stain. Hematopoietic cells ﺳﮯ ﻧﮩﯿﮟ ﻧﮩﯿﮟ ﮨﮯ ﺍﻭﺭ ﺍﺱ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗﮫ ﺍﺳﺘﻌﻤﺎﻝ ﮐﮯ ﺳﺎﺗ Immunohistochemistry or ISH (with bright field and fluorescent) prepared from ccll suspension.
- Amniotic cells stained by FISH (using direct labeled DNA 2. probes for chromosomes X, Y, 13, 18 and 21).
- Cells in urine specimens, stained by FISH (using the Vysis 3. UroVysion™ Bladder Cancer Recurrence Kit for chromosomes 3, 7, 17 and 9p21 locus), from subjects with transitional cell carcinoma of the bladder.

Prescription Use イ (Part 21 C.F.R. 801 Subpart D) AND/OR

Over-The-Counter Use (Part 21 C.F.R. 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Division/Sign-Off

Office of In Vitro Diagnostic Device

Evaluation and Safety

510(k) K050840 7-10