The Duet™ System is an automated scanning microscope and image analysis system. It is intended for in-vitro diagnosis use as an aiding tool to the pathologist in the detection, classification and counting of cells of interests based on particular color, intensity, size, pattern and shape.

The Duet™ System is intended to detect the following cell types:

Hematopoietic cells stained by Giemsa stain, Immunohistochemistry or ISH (with bright field and fluorescent) prepared from cell suspension.
Amniotic cells stained by FISH (using direct labeled DNA probes for chromosomes X, Y, 13, 18 and 21),

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.

AI/ML Overview

Here is the information about the acceptance criteria and the study that proves the device meets the acceptance criteria, based on the provided text:

1. A table of acceptance criteria and the reported device performance

Acceptance Criteria (Stated Goal)	Device Performance
Accuracy: To determine accuracy using the NCCLS-EP9 guideline for method comparison and bias estimation.	Correlation Coefficient: 0.9843 (between Duet™ test and manual method for amniotic fluid cell analysis).Slope: 0.9758Intercept: 2.2316
Precision (Intra-system): To determine precision within a single Duet™ system using the NCCLS-EP5 guideline.	Coefficient of Variation (CV): 0.15% (no clinically significant differences observed)
Precision (Inter-system): To assess differences between readings of the same slides by different Duet™ systems compared to repeated readings on the same system using ANOVA.	No clinically significant differences between systems.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Test Set Sample Size: 133 slides of Amniotic fluid cells from samples of 68 ongoing pregnancies were used for the accuracy study. A set of four slides was used for the precision study.
Data Provenance: The country of origin is not explicitly stated in the provided summary. The study appears to be prospective in nature, as it involved preparing slides and then examining them.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The document primarily compares the Duet™ system's performance to the "routine manual method" or "human manual visualization by conventional microscopes" as a predicate. It does not explicitly state the number of experts or their specific qualifications used to establish the ground truth for the test set. However, it implies that the "manual method" represents the established ground truth.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The document does not describe a specific adjudication method like 2+1 or 3+1. The ground truth for the comparative performance study for accuracy seems to be established by the "routine manual method". It implies a direct comparison rather than an adjudicated consensus.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

A multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described in the provided text. The study focused on comparing the device's performance against the "routine manual method," not on how human readers improve with AI assistance. The document states the Duet™ System is an "aiding tool to the pathologist," but the study described is a direct comparison to manual methods, not an assisted reading study.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone study was performed. The described "Comparison of the routine manual method and the Duet method" and the "Evaluation of precision performance" assess the Duet™ System's performance in its automated capacity without explicit human intervention in the classification and counting steps being measured against the manual method. The device's role is to "suggest classification of the cells," implying the evaluation of its automated capabilities, with the user then allowed to "correct them as needed" which is a post-analysis step.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The type of ground truth used for the accuracy study was implicitly derived from the "routine manual method" of analysis. This suggests that the results obtained by cytogeneticists or pathologists using conventional microscopes were considered the reference standard.

8. The sample size for the training set

The document does not explicitly state the sample size used for the training set of the Duet™ system. It mentions that the "Duet™ System software as a whole was fully validated during its development process," and "Performance studies were accomplished to validate that the software and the system as a whole comply with the new indication," but does not provide details about training data.

9. How the ground truth for the training set was established

The document implicitly states that changes were incorporated to support the new intended use, and the software was validated. However, it does not describe how the ground truth for any potential training set was established.

Summary

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SEP 1 6 2004

510(K) SUMMARY

Duet™ system

510(k) Number Ko4059 I /≤ /

Applicant's Name:

Bioview Ltd. 12 Hamada Street, Rehovot 76703, Israel Tel: 972-8-9366868 Fax: 972-8-9366869

Contact Person:

Dorit Winitz, Ph.D. At: Bioview Ltd. 12 Hamada Street, Rehovot 76703, Israel Tel: 972-8-9366868 Fax: 972-8-9366869 E-mail: vindavid@netvision.net.il

Date Prepared:

July, 2004

Trade Name:

Duet™ System

Classification Name:

Automated cell-location device

Classification:

The FDA has classified Automated cell-locating device as class II devices (product code 81 JOY, Regulation No. 864.5260) and they are reviewed by the Pathology Panel.

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Predicate Device:

· Duet™ System, manufactured by BioView, cleared under K030192
· BandView, manufactured by Applied Spectral Imaging, cleared under K012103.
· Human manual visualization by conventional microscope.

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
. EN-1441: Medical devices – Risk Analysis.
. ISO 14971 Medical Devices-Risk Management

Indications:

The Duet™ Sysetm is intended to detect the following cell types:

1. Hematopoietic cells stained by Giemsa stain, Immunohistochemistry or ISH (with bright field and fluorescent) prepared from cell suspension.
1. Amniotic cells stained by FISH (using direct labeled DNA probes for chromosomes X, Y, 13, 18, and 21).

Device Description:

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

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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 additional indication of amniotic fluid detection, claimed for the a Duet™ System in addition to the previous cleared indications was already claimed for the predicate BandView system.
트 Detection, classification and counting of amniotic fluid cells after FISH are routinely performed manually by cytogeneticist using conventional microscopes.

The Duet™ System employs the same procedures for the detection of amniotic fluid cells after FISH (using direct labeled DNA probes for chromosomes X, Y, 13, 18, and 21) as employed by human manual visualization using conventional microscopes. Additionally, the new amniotic fluid indication was supported by a comparative performance study demonstrating that the operation of the Duet™ System is effective and suitable for the distinction between normal and abnormal amniotic fluid cells in comparison to manual microscopy.

Technological characteristics

The current Duet™ System is the same system as the 510(k)-cleared Duet™ System to which only some non-significant changes were incorporated mainly to support its new intended use. No change in hardware specifications was incorporated.

The Duet™ system, like its predicate devices, is software controlled and includes features such as: acquisition of images, views, editing, relocation, enhancement capabilities, automatic/manual counting and classification, printing, export of images and backups.

The main changes incorporated to the Duet™ System software include the following:

1. An automatic fluorescent scanning of Amniocentesis slides. This option was incorporated in order to support the new indication of the system.
1. Scanning each field of view with several fluorescent filters instead of only one, generating and displaying a combined image for each field of view. The ability to scan each field with only one filter, as was possible with the cleared Duet™ System is still an option in the current device.

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All other minor changes that where incorporated into the software as compared to the cleared Duet™ System are described in details in the System's User's Manual, and in the Duet™ System SRS and SDD documents.

The risks that may be associated with each change were analyzed and after application of the mitigation methods, were found to be acceptable. The mitigation methods employed to contain these risks are standard software process and implementation procedures.

The Duet™ System software as a whole was fully validated during its development process. The results of the comprehensive validation of the software are presented in the System Test Report document.

Performance studies were accomplished to validate that the software and the system as a whole comply with the new indication. The Performance characteristics of the Duet System are described in the following section.

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.

Performance characteristics of the Duet System:

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

Comparison of the routine manual method and the Duet method: The NCCLS-EP9, Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline, was used to determine accuracy. A set of 133 slides of Amniotic fluid cells was prepared using direct labeled DNA probes for chromosomes X, Y, 13, 18, 21 (Vysis, Downers Grove, IL, USA) from samples of 68 ongoing pregnancies. These slides were examined by the routine manual method and by analysis using the Duet System.

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Scatter plots for tested value versus the comparative value and bias plot of the deltas between the values of the Duet™ test and the manual method versus the values of the manual method were performed.

The correlation coefficient was 0.9843 with a slope of 0.9758 and an intercept of 2.2316.

Evaluation of precision performance within a system and across systems: NCCLS-EP5, Evaluation of Precision Performance of Clinical Chemistry Devices: Approved Guideline was used to determine precision. A set of four slides was analyzed, with each slides analyzed on three different systems and three times on one of these systems. The experiment was performed over a period of 14 days.

Intra-system precision showed no clinically significant differences with a Coefficient of Variation (CV) of 0.15%.

ANOVA was used to assess the differences between readings of the same slides by different systems compared to repeated readings of the same system. There were no clinically significant differences between the Duet™ System inter-system precision analyses.

Conclusion

The Duet™ system is substantially equivalent to the combination of the cleared Duet™ System, the BandView system and the human manual procedure of visualization by conventional microscope, in terms of intended use and Indications for Use. The Duet™ System is substantial equivalent in it technological characteristics and mode of operation to the cleared Duet™ System. Any minor differences in technological characteristics between the Duet™ System and its predicate devices do not raise new safety or effectiveness issues, based on the performance results and software validation.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines above a wavy line.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Dorit Winitz, Ph.D Company Consultant BioView Ltd. 12 HaMada St. Rehovot P.O.B. 4051, Nes Ziona 70400 Israel

SEP 1 6 2004

Re: K040591 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: July 06, 2004

Received: July 09, 2004

Dear Dr. Winitz:

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 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.

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Page 2

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Robert L. Becker, Jr.

Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices 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): K040591

Device Name:_Duet™ System

Indications For Use:

The Duet™ System is intended to detect the following cell types:

1. Hematopoietic cells stained by Giemsa stain, Immunohistochemistry or ISH (with bright field and fluorescent) prepared from cell suspension.
Amniotic cells stained by FISH (using direct labeled DNA probes for 2. chromosomes X, Y, 13, 18 and 21),

Prescription Use _ V (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

ia chan for
Josephine Bautista

Division Sign-Off

Office of In Vitro Diganostic Device Evaluation and Safety

510(k) K040571

Regulation Number and Section

§ 864.5260 Automated cell-locating device.

(a)
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.)(b)
Classification. Class II (performance standards).