The CellaVision DM1200 with the Advanced RBC Application 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.

The CellaVision DM1200 with the Advanced RBC Application is intended for blood samples that have been flagged as abnormal by an automated cell counter.

The CellaVision DM1200 with the Advanced RBC Application is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

The CellaVision DM96 with the Advanced RBC Application is an automated cell-locating device, intended for in-vitro diagnostic use.

The CellaVision DM96 with the Advanced RBC Application 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.

The CellaVision DM96 with the Advanced RBC Application is intended for blood samples that have been flagged as abnormal by an automated cell counter.

The CellaVision DM96 with the Advanced RBC Application is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

Device Description

The Advanced RBC Application is substantially equivalent to the RBC functionality included in the predicate DM Systems. It pre-characterizes the morphology of the red blood cells in a sample based on abnormal color, size, and shape (Poikilocytosis). In addition to that, the Advanced RBC Application also pre-characterizes based on different types of Poikilocytosis and on the presence of certain inclusions.

The DM Systems display the result of the RBC pre-characterization as the percentage of abnormal cells for each morphological characteristic and as an automatically calculated grade (0 - normal through 3 - marked), corresponding to that percentage. It also displays an overview image of the RBC monolayer. The difference between the current RBC functionality and Advanced RBC Application is the analysis technique, which enables the Advanced RBC Application to pre-characterize RBC into 21 morphological characteristics as opposed to the current RBC functionality with 6 morphological characteristics. The cell images are pre-characterized into different groups of morphological characteristics based on size, color, shape and inclusion using segmentation, feature calculation and the deterministic artificial neural networks (ANNs) trained to distinquish between morphology characteristics of red blood cells.

Another difference is that the red blood cells, pre-characterized by the Advanced RBC Application, can be displayed both in an overview and in individual images on the screen, while the current RBC functionality displays the pre-characterized red blood cells in an overview image only.

As in the current RBC functionality, the user reviews the overview image and can change the characterization by manually changing the grades for any morphological characteristic. With the Advanced RBC Application, the user can also view individual cells, grouped by morphological characteristic and change the characterization by reclassifying individual cells.

AI/ML Overview

The provided text describes the CellaVision DM96 and DM1200 with Advanced RBC Application, an automated cell-locating device. Here's a breakdown of the requested information based on the text:

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

The document states that a clinical evaluation was conducted, and the results "met the predefined acceptance criteria" for various metrics. However, the precise quantitative acceptance criteria and the exact reported performance values are not explicitly stated in this summary. The summary only mentions that the results fulfilled the acceptance criteria.

Metric (Morphology Group)	Acceptance Criteria	Reported Device Performance
RBC group Size	Overall Agreement, Positive Percent Agreement (PPA), Negative Percent Agreement (NPA)	"fulfilled the acceptance criteria"
Groups Color, Shape, Inclusions, and clinical significant morphologies	Efficiency, Sensitivity, Specificity	"fulfilled the acceptance criteria"
Individual morphological characteristics	Sensitivity, Specificity	"fulfilled the target limits"

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

Sample size: The document states, "Samples were collected and tested for RBC characterization on DM96 and DM1200 at different laboratories." However, the exact sample size for the clinical evaluation (test set) is not specified.
Data provenance: The samples were collected "from routine workflow from hospital laboratories" and "in accordance with the target patient population, i.e. from samples flagged as abnormal by an automated cell counter." This suggests prospective collection from clinical settings, but specific countries of origin are not mentioned.

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)

For the clinical evaluation, the "manual microscopy (Reference Method)" was used as the primary comparator for most morphology groups. For the "RBC group Size," an "automated cell counter" was used as a "convenient predicate device."

The document implies that the ground truth for most RBC characteristics was established by manual microscopy, which would involve human experts. However, the number of experts and their specific qualifications are not provided. The device's intended use states, "The CellaVision DM96/DM1200 with the Advanced RBC Application is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells," which implies that the reference method would also involve such skilled operators.

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

The document does not specify an adjudication method for establishing the ground truth from manual microscopy or for resolving discrepancies between readers (if multiple readers were used). It simply refers to "manual microscopy (Reference Method)" as the comparator.

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

No, an MRMC comparative effectiveness study was not explicitly described in the provided text. The study conducted was a comparison between the automated device (CellaVision Advanced RBC Application) and manual microscopy (Reference Method), not a study evaluating human reader improvement with AI assistance.
The device "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." While the device assists the human, the study's objective was about the equivalence of the device's characterization results to manual microscopy, not the improvement of human readers.

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

No, a standalone (algorithm only) performance study was not described. The device is explicitly designed for a human-in-the-loop workflow: "The operator identifies and verifies the suggested classification of each cell according to type." Therefore, the evaluation would inherently include this human interaction. The clinical evaluation compared the "Advanced RBC Application installed on CellaVision DM96 and CellaVision DM1200 (Test Methods)" to the manual method, implying system performance with human verification.

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

The ground truth used was primarily:

Expert consensus from manual microscopy for most RBC morphological characteristics.
Automated cell counter results for the "RBC group Size" (Macrocytes, Microcytes, and Anisocytosis), as manual microscopy was deemed "highly difficult, time consuming and thereby impractical" for this group.

8. The sample size for the training set

The document does not specify the sample size used for the training set of the deterministic artificial neural networks (ANNs). It only mentions that the ANNs were "trained to distinguish between morphology characteristics of red blood cells."

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

The document does not explicitly state how the ground truth for the training set was established. It mentions that the ANNs were "trained to distinguish between morphology characteristics of red blood cells," implying that labeled data was used for training, but the method of obtaining these labels (e.g., expert annotations, specific pathological confirmation) is not detailed.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of three faces in profile, stacked on top of each other.

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

August 1, 2017

CellaVision AB c/o Constance G. Bundy C G Bundy LLC 435 Rice Creek Terrace NE Fridley, MN 55432

Re: K171315

Trade/Device Name: CellaVision DM96 and DM1200 with Advanced RBC Application Regulation Number: 21 CFR 864.5260 Regulation Name: Automated cell-locating device Regulatory Class: Class II Product Code: JOY Dated: April 30, 2017 Received: May 4, 2017

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 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 comply with all the Act's requirements, including, but not limited to: registration and listing (21

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CFR Part 807); labeling (21 CFR Parts 801 and 809); 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 contact the Division of Industry and Consumer Education 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. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely.

Leonthena R. Carrington -S

Lea Carrington, MS, MBA, MT(ASCP) 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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4 Indications for Use Statement

DEPARTMENT OF HEALTH AND HUMAN SERVICES	Form Approved: OMB No. 0910-0120
Food and Drug Administration	Expiration Date: January 31, 2017
Indications for Use	See PRA Statement below.

510(k) Number (if known)

Device Name

CellaVision DM96 and DM1200 with Advanced RBC Application

Indications for Use (Describe)

The Cella Vision DM1200 with the Advanced RBC Application is an automated cell-locating device, intended for in-irtro diagnostic use.

The CellaVision DM1200 with the Advanced RBC Application is intended for blood samples that have been flagged as abnormal by an automated cell counter.

The CellaVision DM1200 with the Advanced RBC Application is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

The Cella Vision DM96 with the Advanced RBC Application is an automated cell-locating device, intended for in-vitro diagnostic use.

The Cella Vision DM96 with the Advanced RBC Application 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.

The Cella Vision DM96 with the Advanced RBC Application is intended for blood samples that have been flagged as abnormal by an automated cell counter.

The CellaVision DM96 with the Advanced RBC Application is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

Type of Use (Select one or both, as applicable)
```html Type of Use (Select one or both, as applicable) ☑ Prescription Use (Part 21 CFR 801 Subpart D)☐ Over-The-Counter Use (21 CFR 801 Subpart C)	Type of Use (Select one or both, as applicable)	☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.'

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

FORM FDA 3881 (8/14)

Page of

PSC Publishing Services (301) 443-6740 EF

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510(k) Summary

This 510(k) summary is being submitted in accordance with the requirements of 21 CFR807.92.

510(k) Number

K171315

. SUBMITTER

CellaVision AB Ideon Science Park SE-223 70 Lund Sweden Phone: +46 46 286 44 00 Fax: +46 46 286 44 70

Contact Person: Constance G. Bundy CG Bundy LLC 435 Rice Creek Terrace NE Fridley. MN 55432 USA Phone: 763-574-1976
April 30, 2017 Date Prepared:

DEVICE ll.

Name of Device: Advanced RBC Application Common or Usual Name: Automated cell-locating device Classification Name: Automated cell-locating device (21 CFR 864.5260) Requlatory Class: . Product Code: JOY

. PREDICATE DEVICES

a) Romanowsky stain manual light microscope process for cell classification (21CFR 864.3600 Class I exempted from pre-market notification procedure).
b) RBC functionality of the Peripheral Blood Application of the CellaVision DM Software installed on the legally marketed DM Systems, DM96 (K033840) and DM1200 (K092868).

IV DEVICE DESCRIPTION

The Advanced RBC Application is substantially equivalent to the RBC functionality included in the predicate DM Systems. It pre-characterizes the morphology of the red

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blood cells in a sample based on abnormal color, size, and shape (Poikilocytosis). In addition to that, the Advanced RBC Application also pre-characterizes based on different types of Poikilocytosis and on the presence of certain inclusions.

V. INTENDED USE

The CellaVision DM1200 with the Advanced RBC Application is an automated celllocating device, intended for in-vitro diagnostic use.

The CellaVision DM1200 with the Advanced RBC Application is intended for blood samples that have been flagged as abnormal by an automated cell counter.

The CellaVision DM1200 with the Advanced RBC Application is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

The CellaVision DM96 with the Advanced RBC Application is an automated cell-locating device, intended for in-vitro diagnostic use.

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The CellaVision DM96 with the Advanced RBC Application is intended for blood samples that have been flagged as abnormal by an automated cell counter.

The CellaVision DM96 with the Advanced RBC Application is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells.

COMPARISON OF THE ADVANCED RBC APPLICATION WITH THE VI. PREDICATE DEVICES

Table 0:1 Comparison table

Characteristic	Manual light microscopicprocess	DM Systems	DM Systems with AdvancedRBC Application
Intended use	Manual method for cell-locating and identification ofred blood cells fromperipheral blood smears.Verification of results byskilled human operator.	DM Systems is an automatedcell-locating device, intendedfor in-vitro diagnostic use.DM Systems automaticallylocates and presents imagesof blood cells on peripheralblood smears. The operatoridentifies and verifies thesuggested classification ofeach cell according to type.DM Systems is intended to beused by skilled operators,trained in the use of thedevice and in recognition ofblood cells.	DM Systems with theAdvanced RBC Application isan automated cell-locatingdevice, intended for in-vitrodiagnostic use.DM Systems with theAdvanced RBC Applicationautomatically locates andpresents images of bloodcells on peripheral bloodsmears. The operatoridentifies and verifies thesuggested classification ofeach cell according to type.DM Systems with theAdvanced RBC Application isintended for blood samplesthat have been flagged asabnormal by an automatedcell counter.DM Systems with theAdvanced RBC Application isintended to be used by skilledoperators, trained in the useof the device and inrecognition of blood cells.
Intended usepopulation	The intended use populationis patients whose bloodsamples have been flaggedas abnormal by an automatedcell counter.	The intended use populationis patients whose bloodsamples have been flaggedas abnormal by an automatedcell counter.	The intended use populationis patients whose bloodsamples have been flaggedas abnormal by an automatedcell counter.
Specimen type	Peripheral blood.	Peripheral blood.	Peripheral blood.
Samplepreparation	Romanowsky stained bloodfilm on glass slides ofperipheral whole blood.	Romanowsky stained bloodfilm on glass slides ofperipheral whole blood.	Romanowsky stained bloodfilm on glass slides ofperipheral whole blood.
Characteristic	Manual light microscopicprocess	DM Systems	DM Systems with AdvancedRBC Application
Analysistechnique	The examiners characterizered blood cell morphologyfrom an overview based onsize, color, shape andinclusion.	The device presents anoverview image.The cell images are pre-characterized into 6 differentmorphological characteristicsbased on size color andshape using segmentation,feature calculation andclassification (decision tree):	The device presents anoverview image.The cell images are pre-characterized into 21 differentmorphological characteristicsbased on size, color, shapeand inclusion usingsegmentation, featurecalculation and thedeterministic artificial neuralnetworks (ANNs) trained todistinguish betweenmorphology characteristics ofred blood cells.
Pre-characteriztion	N/A	The cell images are pre-characterized into thefollowing morphologies:- Polychromatic cells;- Hypochromatic cells;- Anisocytosis;- Microcytes;- Macrocytes; and- Poikilocytosis.	The cell images are pre-characterized into thefollowing morphologies:- Polychromatic cells;- Hypochromatic cells;- Anisocytosis;- Microcytes;- Macrocytes:- Poikilocytosis;- Target cells:- Schistocytes;- Helmet cells;- Sickle cells;- Spherocytes;- Elliptocytes;- Ovalocytes;- Tear drop cells;- Stomatocytes;- Acanthocytes;- Echinocytes;- Howell-Jolly bodies;- Pappenheimer bodies;- Basophilic stippling; and- Parasites.
User-definedcharacteristics	N/A	The operator can furthercharacterize into 10 user-defined characteristics.	The operator can furthercharacterize into 10 user-defined characteristics.
Verification ofresults	N/A	The operator verifies thesuggested morphologicalcharacteristics by acceptingor re-characterizing.	The operator verifies thesuggested morphologicalcharacteristics by acceptingor re-characterizing.
510(k) numbers	510(k) exempt (864.3600)	K033840 (DM96)	N/A

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PERFORMANCE DATA VII.

The following performance data were provided in support of the substantial equivalence determination.

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Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and Staff, "Guidance for the Content of premarket Submissions for Software Contained in Medical Devices." The software application was considered as a "moderate" level of concern, since a malfunction failure or latent design flaw in the software could lead to an erroneous diagnosis or a delay in delivery of appropriate medical care that could lead to a minor injury.

Reproducibility and repeatability

The reproducibility study was performed at three sites with samples collected from routine workflow from hospital laboratories including normal and elevated levels for each of the 21 RBC morphological characteristics. The reproducibility study was based on the CLSI EP05-A3 guidance document. From each sample, 3 slides were prepared. The slides were then run at each site 2 times a day for 5 days. The grading reproducibility was calculated by determining the relation between the occurrence of true grade and the total number of runs. The proportional cell count in percent for each morphological characteristic was used to estimate total variance and variance components for within-run (i.e. repeatability), between-run, and between-day and between-site based on CLSI EP05-A3. The results met the predefined acceptance criteria.

The repeatability study was performed according to the CLSI EP05-A3 guidance document. Samples were run 2 times a day with 2 replicates per run for 20 days on both DM96 and DM1200. The study was designed to provide repeatability data for both qualitative results (i.e. grade 0, 1, 2 and 3) and quantitative results (i.e. proportional count) for each morphological characteristic. The grading agreement was calculated for each slide and for each sample by determining the relation between the occurrence of true grade and the total number of runs for each morphological characteristic. The proportional cell count in percent for each morphological characteristic was used to estimate total variance and variance components for repeatability (i.e. within-run), between-run, and between-day based on CLSI EP05-A3. The results met the predefined acceptance criteria.

Clinical Evaluation

A comparison study was conducted comparing the Advanced RBC Application installed on CellaVision DM96 and CellaVision DM1200 (Test Methods) with the manual microscopy (Reference Method). For characterization of the RBC group Size (i.e Macrocytes, Microcytes and Anisocytosis), the manual microscopy as a standard reference is highly difficult, time consuming and thereby impractical. Therefore, an automated cell counter, as a more convenient predicate device (non-reference standard) was used.

The study was performed based on the approved quidance document CLSI H20-A2. Samples were collected and tested for RBC characterization on DM96 and DM1200 at different laboratories. The samples included blood samples, collected in accordance

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with the target patient population, i.e. from samples flagged as abnormal by an automated cell counter.

The objective of the evaluation was to show that the RBC characterization results using the CellaVision Advanced RBC Application are equivalent with results achieved using the comparative method.

The comparison study demonstrates that for the morphology group Size the overall agreement as well as positive percent agreement (PPA) and negative percent agreement (NPA), fulfilled the acceptance criteria for samples run on the DM Systems. For the groups Color, Shape, Inclusions and the clinical significant morphologies the efficiency, sensitivity and specificity, fulfilled the acceptance criteria. Further, the study demonstrates that the sensitivity and specificity for the individual morphological characteristics fulfilled the target limits.

Based on the clinical performance as documented in the clinical study, the Advanced RBC Application was found to have a safety and effectiveness profile that is similar to the predicate device.

VIII CONCLUSION

Based on extensive testing, including comparison to the predicate devices, it is the conclusion of CellaVision AB that the DM Systems with the Advanced RBC Application are substantially equivalent to devices already on the market and do not raise any new questions regarding safety and effectiveness.

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).