DM96 automatically locates and presents images of blood cells on peripheral blood smears. The operator identifies and verifies the suggested classification of each cell according to type.

DM96 is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

Device Description

DM96 is an automated cell-locating device for differential count of white blood cells, characterization of red blood cell morphology and platelet estimation. DM96 consists of a slidescanning unit (a slide feeder, a microscope and a camera) and a computer system containing the acquisition and classification software "CellaVision Blood Differential software".

AI/ML Overview

Here's an analysis of the provided text, extracting the requested information about device acceptance criteria and the supporting study:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state numerical acceptance criteria. Instead, it frames the performance in terms of "equivalence" to the predicate device (DiffMaster Octavia™) and the manual light microscopic process. The reported performance is that the DM96 "is equivalent in accuracy, precision and clinical sensitivity and specificity and fulfilled the pre-defined requirements for overview image quality."

Characteristic	Acceptance Criteria (Implied)	Reported Device Performance
Accuracy (White Blood Cell Classification)	Equivalent to DiffMaster Octavia™ and manual light microscopic process	Achieved equivalence to predicate and manual method
Precision (White Blood Cell Classification)	Equivalent to DiffMaster Octavia™ and manual light microscopic process	Achieved equivalence to predicate and manual method
Clinical Sensitivity (White Blood Cell Classification)	Equivalent to DiffMaster Octavia™ and manual light microscopic process	Achieved equivalence to predicate and manual method
Clinical Specificity (White Blood Cell Classification)	Equivalent to DiffMaster Octavia™ and manual light microscopic process	Achieved equivalence to predicate and manual method
Cell-Location Accuracy	Met pre-defined requirements	Achieved accuracy for cell-location
Overview Image Quality	Met pre-defined requirements	Fulfilled pre-defined requirements for overview image quality

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

The document does not explicitly state the sample size used for the clinical evaluation (test set) or the data provenance (e.g., country of origin, retrospective/prospective). It only mentions that "A clinical evaluation has been performed to confirm equivalence with the predicate method DiffMaster Octavia™ for differentiation of white blood cells."

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

This information is not provided in the document.

4. Adjudication Method for the Test Set

The document states that for both the predicate device and the DM96, "A competent operator is required to confirm or modify the suggested classification of each cell." This indicates a human-in-the-loop approach where human verification or reclassification is part of the final result. However, the specific adjudication method used for the initial ground truth (e.g., 2+1, 3+1 consensus) for the test set is not explicitly described.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

The document describes a clinical evaluation to confirm equivalence with a predicate method, which is a comparative study. It also explicitly states that the device is intended for use by "skilled operators, trained in the use of the device and in recognition of blood cells," and that "The operator identifies and verifies the suggested classification of each cell according to type." This implies a human-in-the-loop scenario.
However, it does not explicitly state that it was a formal MRMC study, nor does it provide an effect size of how much human readers improve with AI vs. without AI assistance. The study focuses on demonstrating equivalence of the DM96 (with human verification) to existing methods.

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

The device description consistently states that the "operator identifies and verifies the suggested classification of each cell." The technological characteristics section further elaborates that "The cell images are pre-classified and the operator verifies the suggested classification by accepting or reclassifying." This indicates that the device is not intended or tested for standalone, algorithm-only performance without a human-in-the-loop to verify classifications.

7. The Type of Ground Truth Used

The ground truth for the clinical evaluation appears to be based on expert consensus from a "competent human examiner" or "skilled operators" using either the manual light microscopic process or the predicate device (DiffMaster Octavia™) for comparison. The study aimed to show equivalence to these established methods, which rely on human expert interpretation.

8. Sample Size for the Training Set

The document provides no information regarding the sample size used for the training set of the deterministic artificial neural networks (ANNs).

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

The document states that ANNs are "trained to distinguish between classes of white blood cells." However, it does not describe how the ground truth for this training data was established.

Summary

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Section 2. SUMMARY AND CERTIFICATION

2.1. 510 (k) Summary

2.1.1. Summary of Safety and Effectiveness

In accordance with 21 CFR 807.92, the following information constitutes the 510(k) summary for DM96.

SUBMITTER'S NAME:	CellaVision AB
ADDRESS:	Ideon Research Park, SE-223 70 Lund, Sweden
CONTACT PERSON:	Constance G. Bundy
TELEPHONE NUMBER:	763-574-1976
FAX NUMBER:	763-571-2437
DATE OF SUBMISSION:	December 9, 2003

1. Identification of device

Proprietary Name: CellaVision DM96 Automatic Hematology Analyzer Common Name: DM96 Classification Status: Class II per regulations 21CFR 864.5260 Product Codes: JOY

2. Equivalent devices

CellaVision AB believes DM96 is substantially equivalent to the Romanowsky stain manual light microscopic process for cell classification (21CFR 864.3600 Class I exempted from premarket notification procedure) and DiffMaster Octavia™ Hematology Analyzer, 510(k) number K003301, CellaVision AB.

3. Description of the device

4. Intended use

DM96 is an automated cell-locating device.

DM96 automatically locates and presents images of blood cells on peripheral blood smears. The operator identifies and verifies the suggested classification of each cell according to type.

DM96 is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

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5. Technological characteristics, comparison to predicate device

Like the predicate device, DM96 locates white blood cells, stores digital images of the cells and displays the images in an organized manner and suggests a cell class for each cell to aid operators in performing the differential count procedure. A competent operator is required to confirm or modify the suggested classification of each cell. It is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells. Like the predicate device, DM96 presents an overview image from which it is possible to characterize red blood cells regarding size, shape and color. In addition, the DM96 presents an overview image and facilitates platelet estimation.

Brief discussion of non-clinical factors supporting a determination of substantial equivalence: The method requires a competent human examiner to review the microscopic images of the cells as does the predicate method and device. See substantial equivalence comparisons below.

Brief discussion of clinical tests supporting a determination of substantial equivalence: A clinical evaluation has been performed to confirm equivalence with the predicate method DiffMaster Octavia™ for differentiation of white blood cells. The study has been performed according to a predefined protocol based upon the approved standard, NCCLS, vol. 23, no 1, document H-20A. March 1992: Reference Leukocyte Differential Count (proportional) and Evaluation of Instrumental Method. Complementary tests have been performed to confirm celllocation, precision and overview image quality.

Conclusions drawn from clinical tests:

The following information was obtained from the clinical tests:

· accuracy for cell-location
· accuracy for the verified classification for each cell class
· precision for the verified classification for each cell class
· clinical sensitivity and specificity

The results show that the DM96 is equivalent in accuracy, precision and clinical sensitivity and specificity and fulfilled the pre-defined requirements for overview image quality.

Characteristic	Manual lightmicroscopic process	DiffMaster Octavia™ DM 96
Intended use	Manual method forcell-location andidentification, for in-vitro use.Verification of resultsby human operator.	Automated cell-locating device forcell-location, andidentification, for in-vitro use.Verification of resultsby human operator.	Automated cell-locating device forcell-location, andidentification, for in-vitro use.Verification of resultsby human operator.
Sample type	Stained blood film onglass slides ofperipheral wholeblood.	Stained blood film onglass slides ofperipheral wholeblood.	Stained blood film onglass slides ofperipheral wholeblood.
Characteristic	Manual lightmicroscopic process	DiffMaster Octavia™	DM 96
Samplepreparation	Romanowsky stain	Romanowsky stain	Romanowsky stain
Analysistechnique	White blood cells:The examiners usuallylocate/count whiteblood cells by movingaccording to thebattlement trackpattern on the smearand distinguishbetween classes ofwhite blood cells.	White blood cells:Cells arelocated/counted bymoving according tothe battlement trackpattern. Cell imagesare analyzed usingstandard mathematicalmethods, includingdeterministic artificialneural networks(ANN's) trained todistinguish betweenclasses of white bloodcells.The cell images arepre-classified and theoperator verifies thesuggestedclassification byaccepting orreclassifying.	White blood cells:Cells arelocated/counted bymoving according tothe battlement trackpattern. Cell imagesare analyzed usingstandard mathematicalmethods, includingdeterministic artificialneural networks(ANN's) trained todistinguish betweenclasses of white bloodcells.The cell images arepre-classified and theoperator verifies thesuggestedclassification byaccepting orreclassifying.
	Red blood cells:The examinerscharacterize red bloodcell morphology froman overview.	Red blood cells:The device presents anoverview image.The examinerscharacterize red bloodcell morphology fromthe image.	Red blood cells:The device presents anoverview image.The examinerscharacterize red bloodcell morphology fromthe image.
	Platelets:The examinersmanually count andestimate the plateletconcentration from anoverview according toa standardizedprocedure (21 CFR864.6160 Manualblood cell countingdevice, Class I).		Platelets:The device presents anoverview image.The examinersmanually count andestimate the plateletconcentration from theoverview imageaccording to astandardizedprocedure.

Comparative features of DM96 compared with the predicate devices:

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6. Discussion of Performance Testing.

An extensive collection of tests has been conducted and successfully completed, including tests to ensure safety, effectiveness, and compliance with product requirements.

The following tests were conducted and successfully completed:

a) Evaluation of:

Performance (accuracy and precision, clinical sensitivity, specificity, cell-location)
Safety

b) Inspections to verify that all design features are as intended and that all authorized design changes have been accomplished and recorded.

c) Validation of the system (including efficacy of user interface)

7. Conclusion

Based on extensive performance testing and a comparison to the predicate device, it is the conclusion of CellaVision AB that DM96 is substantially equivalent to devices already on the market (cleared by the 510(k) process) and presents no new concerns about safety and effectiveness.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/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 three stripes forming its body and wings. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administratio 2098 Gaither Road Rockville MD 20850

FEB 1 0 2004

CellaVision AB c/o Ms. Constance G. Bundy C. G. Bundy Associates, Inc. 6740 Riverview Terrace Minneapolis, MN 55432

Re: K033840

Trade/Device Name: CellaVision DM96 Regulation Number: 21 CFR 864.5260 Regulation Name: Automated cell-locating device Regulatory Class: Class II Product Code: JOY: GKZ Dated: December 9, 2003 Received: December 10, 2003

Dear Ms. Bundy:

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 adultcration.

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).

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Page 2

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.

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.

Aven Antman, m.D.

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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1.2. Indications for Use

510(k) Number_ K 033840

Device Name: CellaVision DM96

Indications for Use:

DM96 is an automated cell-locating device.

DM96 automatically locates and presents images of blood cells on peripheral blood smears. The operator identifies and verifies the suggested classification of each cell according to type.

DM96 is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

(Please do not write below this line - continue on another page if needed)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use ﺳ (Per 21 CFR 801.109)

Over the Counter Use_ ________________________________________________________________________________________________________________________________________________________

Maria Chen for Joseph Bautista
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K 053840

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).