Advanced RBC Application

K171315 · CellaVision AB · JOY · Aug 1, 2017 · Hematology

Device Facts

• Record ID: K171315
• Device Name: Advanced RBC Application
• Applicant: CellaVision AB
• Product Code: JOY · Hematology
• Decision Date: Aug 1, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5260
• Device Class: Class 2
• Attributes: AI/ML

Intended Use

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

System consists of slide scanning unit (microscope, camera, feeder) and computer with acquisition/classification software. Input: Romanowsky-stained peripheral blood smears on glass slides. Process: System scans slide, locates cells, and uses artificial neural networks (ANNs) to pre-characterize RBCs into 21 morphological categories based on size, color, shape, and inclusions. Output: Overview images and individual cell images presented on screen; suggested morphological grades (0-3) and relative distribution percentages. Operator reviews, verifies, or modifies classifications; signs results. Used in clinical laboratories by trained operators. Benefits: Automates tedious manual RBC morphology review; provides standardized pre-characterization to assist clinical decision-making regarding anemia or other hematological conditions.

Clinical Evidence

Multi-site study (5 sites, 1598 samples) compared Advanced RBC Application against manual microscopy and automated cell counters. Primary evaluation (color, shape, inclusion) showed efficiencies of 87.7%, 88.5%, and 94.4% respectively. Secondary evaluation of clinically significant morphologies showed 90.6% efficiency. Precision studies (repeatability/reproducibility) across three sites confirmed consistent grading performance across 21 morphological characteristics. No clinical outcomes data; performance based on analytical agreement with expert manual review.

Technological Characteristics

System includes slide scanning unit (microscope, camera, feeder) and computer. Software utilizes deterministic artificial neural networks (ANNs) for image classification. Connectivity: LIS integration via barcode. Sterilization: Not applicable (slide preparation is external). Dimensions/Form factor: Desktop analyzer. Software: Embedded module within CellaVision DM Software.

Indications for Use

Indicated for patients whose peripheral blood samples have been flagged as abnormal by an automated cell counter, requiring morphological review of red blood cells by skilled operators.

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

• Manual Light Microscope with a Romanowsky stain
• CellaVision DM96 (K033840)
• CellaVision DM1200 Automated Hematology Analyzer (K092868)

Submission Summary (Full Text)

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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 [phone] or [phone] 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 [phone] or [phone] 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 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 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) | | | | |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|--|-------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| <div style="display:flex; align-items:center;"><div> ```html <div> <table><tr><td>Type of Use (Select one or both, as applicable)</td><td></td></tr></table> <table><tr><td><span style="display:inline-block;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D)</td><td><span style="display:inline-block;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C)</td></tr></table> </div></div></div> | Type of Use (Select one or both, as applicable) | | <span style="display:inline-block;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) | <span style="display:inline-block;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) |
| Type of Use (Select one or both, as applicable) | | | | |
| <span style="display:inline-block;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) | <span style="display:inline-block;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) | | | |

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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: [phone] Fax: [phone]

- Contact Person: Constance G. Bundy CG Bundy LLC 435 Rice Creek Terrace NE Fridley. MN 55432 USA Phone: [phone]
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.

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.

#### 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 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.

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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.

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

### Table 0:1 Comparison table

| Characteristic | Manual light microscopic<br>process | DM Systems | DM Systems with Advanced<br>RBC Application |
|---------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | Manual method for cell-<br>locating and identification of<br>red blood cells from<br>peripheral blood smears.<br>Verification of results by<br>skilled human operator. | DM Systems is an automated<br>cell-locating device, intended<br>for in-vitro diagnostic use.<br>DM Systems automatically<br>locates and presents images<br>of blood cells on peripheral<br>blood smears. The operator<br>identifies and verifies the<br>suggested classification of<br>each cell according to type.<br>DM Systems is intended to be<br>used by skilled operators,<br>trained in the use of the<br>device and in recognition of<br>blood cells. | DM Systems with the<br>Advanced RBC Application is<br>an automated cell-locating<br>device, intended for in-vitro<br>diagnostic use.<br>DM Systems with the<br>Advanced RBC Application<br>automatically locates and<br>presents images of blood<br>cells on peripheral blood<br>smears. The operator<br>identifies and verifies the<br>suggested classification of<br>each cell according to type.<br>DM Systems with the<br>Advanced RBC Application is<br>intended for blood samples<br>that have been flagged as<br>abnormal by an automated<br>cell counter.<br>DM Systems with the<br>Advanced RBC Application is<br>intended to be used by skilled<br>operators, trained in the use<br>of the device and in<br>recognition of blood cells. |
| Intended use<br>population | The intended use population<br>is patients whose blood<br>samples have been flagged<br>as abnormal by an automated<br>cell counter. | The intended use population<br>is patients whose blood<br>samples have been flagged<br>as abnormal by an automated<br>cell counter. | The intended use population<br>is patients whose blood<br>samples have been flagged<br>as abnormal by an automated<br>cell counter. |
| Specimen type | Peripheral blood. | Peripheral blood. | Peripheral blood. |
| Sample<br>preparation | Romanowsky stained blood<br>film on glass slides of<br>peripheral whole blood. | Romanowsky stained blood<br>film on glass slides of<br>peripheral whole blood. | Romanowsky stained blood<br>film on glass slides of<br>peripheral whole blood. |
| Characteristic | Manual light microscopic<br>process | DM Systems | DM Systems with Advanced<br>RBC Application |
| Analysis<br>technique | The examiners characterize<br>red blood cell morphology<br>from an overview based on<br>size, color, shape and<br>inclusion. | The device presents an<br>overview image.<br><br>The cell images are pre-<br>characterized into 6 different<br>morphological characteristics<br>based on size color and<br>shape using segmentation,<br>feature calculation and<br>classification (decision tree): | The device presents an<br>overview image.<br><br>The cell images are pre-<br>characterized into 21 different<br>morphological characteristics<br>based on size, color, shape<br>and inclusion using<br>segmentation, feature<br>calculation and the<br>deterministic artificial neural<br>networks (ANNs) trained to<br>distinguish between<br>morphology characteristics of<br>red blood cells. |
| Pre-<br>characteriztion | N/A | The cell images are pre-<br>characterized into the<br>following morphologies:<br><br>- Polychromatic cells;<br>- Hypochromatic cells;<br>- Anisocytosis;<br>- Microcytes;<br>- Macrocytes; and<br>- Poikilocytosis. | The cell images are pre-<br>characterized into the<br>following morphologies:<br><br>- Polychromatic cells;<br>- Hypochromatic cells;<br>- Anisocytosis;<br>- Microcytes;<br>- Macrocytes:<br>- Poikilocytosis;<br>- Target cells:<br>- Schistocytes;<br>- Helmet cells;<br>- Sickle cells;<br>- Spherocytes;<br>- Elliptocytes;<br>- Ovalocytes;<br>- Tear drop cells;<br>- Stomatocytes;<br>- Acanthocytes;<br>- Echinocytes;<br>- Howell-Jolly bodies;<br>- Pappenheimer bodies;<br>- Basophilic stippling; and<br>- Parasites. |
| User-defined<br>characteristics | N/A | The operator can further<br>characterize into 10 user-<br>defined characteristics. | The operator can further<br>characterize into 10 user-<br>defined characteristics. |
| Verification of<br>results | N/A | The operator verifies the<br>suggested morphological<br>characteristics by accepting<br>or re-characterizing. | The operator verifies the<br>suggested morphological<br>characteristics by accepting<br>or 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.