(224 days)
CellaVision® DC-1 is an automated cell-locating device intended for in-vitro diagnostic use in clinical laboratories.
CellaVision® DC-1 is intended to be used by operators, trained in the use of the device.
Intended use of the Peripheral Blood Application
The Peripheral Blood Application is intended for differential count of white blood cells (WBC), characterization of red blood cell (RBC) morphology and platelet estimation.
The CellaVision® DC-1 with the Peripheral Blood Application automatically locates blood cells on peripheral blood (PB) smears. The application presents images of the blood cells for review. A skilled operator trained in recognition of blood cells, identifies and verifies the suggested classification of each cell according to type.
The CellaVision® DC-1 is an automated cell-locating device intended for in-vitro diagnostic use. CellaVision® DC-1 automatically locates and presents images of blood cells found on peripheral blood smears. The operator identifies and verifies the suggested classification of each cell according to type. CellaVision® DC-1 is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells
The CellaVision® DC-1 consists of a built-in PC with a Solid-State Disc (SSD) containing CellaVision DM Software (CDMS), a high-power magnification microscope with a LED illumination, an XY stage, a proprietary camera with firmware, built-in motor- and illumination LED controller, a casing and an external power supply. It is capable of handling one slide at a time.
Here's a detailed breakdown of the acceptance criteria and study information for the CellaVision® DC-1 device, based on the provided text:
Acceptance Criteria and Device Performance
| Parameter | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| WBC Repeatability | Proportional cell count in percent for each cell class. All tests except repeatability and within laboratory precision on three occasions met acceptance criteria. Variation in mean values between slide 1 and 2 for specific cell types should not exceed acceptance criteria. | Overall successful. Three samples displayed variation in mean values between slide 1 and 2 for specific cell types, resulting in a variation slightly above acceptance criteria. |
| RBC Repeatability | Agreement (percentage of runs reporting the grade) for each morphology. Variation in mean values between slide 1 and 2 for specific cell types should not exceed acceptance criteria. | Overall successful. One sample displayed variation in mean value between slide 1 and 2 for the specific cell type, resulting in a variation above acceptance criteria. |
| PLT Repeatability | Agreement (percentage of runs reporting the actual PLT level) for each PLT level. | Met the acceptance criterion in all samples at all three sites. |
| WBC Reproducibility | Not explicitly stated in quantitative terms but implied to be successful based on ANOVA on proportional cell count for each class. | Overall successful. |
| RBC Reproducibility | Not explicitly stated in quantitative terms but implied to be successful based on agreement (percentage of runs reporting the grade). | Overall successful. |
| PLT Reproducibility | Agreement (percentage of runs reporting the most prevalent level) for each PLT level. | Met the acceptance criterion in all samples. Overall successful. |
| WBC Comparison (Accuracy) | Linear regression slope: 0.8-1.2. Intercept: ±0.2 for individual cell types with a normal level of >5%. | Accuracy evaluations successful in all studies, showing no systematic difference between DC-1 and DM1200. Agreement for Segmented Neutrophils, Lymphocytes, Eosinophils, and Monocytes were all within acceptance criteria. |
| WBC Comparison (Distribution & Morphology) | Not explicitly stated, but PPA, NPA, and OA percentages are reported for comparison to predicate. | Distribution: OA 89.8%, PPA 89.2%, NPA 90.4%. Morphology: OA 91.3%, PPA 88.6%, NPA 92.5%. |
| RBC Comparison | Not explicitly stated, but PPA, NPA, and OA percentages are reported for comparison to predicate with 95% CI. | Color: OA 79.9% (76.4%-82.9%), PPA 87.8% (82.3%-91.8%), NPA 76.3% (71.9%-80.2%). Size: OA 88.2% (85.3%-90.6%), PPA 89.8% (86.3%-92.2%), NPA 84.8% (79.0%-89.2%). Shape: OA 85.2% (82.0%-87.8%), PPA 87.3% (82.3%-91.0%), NPA 83.8% (79.6%-87.3%). |
| PLT Comparison | Cohen's Kappa coefficient ≥ 0.6. | Weighted Kappa 0.89405 (95% CI: 0.87062 to 0.91748), meeting the acceptance criterion. |
| EMC Testing | Conformity with IEC 61010-1:2010 and IEC 61010-2-101:2015. | The test showed that the DC-1 is in conformity with IEC 61010-1:2010 and IEC 61010-2-101:2015. |
| Software V&V | Software verification and validation testing documentation provided as recommended by FDA. | Documentation was provided as recommended by FDA's Guidance for Industry and Staff. Software classified as "moderate" level of concern. |
Study Details
-
Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- WBC Comparison: 598 samples (1196 slides, A and B slide).
- RBC Comparison: 586 samples.
- PLT Comparison: 598 samples.
- Repeatability and Reproducibility studies:
- WBC & RBC Repeatability: Five samples at each of three sites.
- PLT Repeatability: Four samples at each of three sites.
- WBC Reproducibility: Five samples, five slides prepared from each, processed daily at three sites for five days.
- RBC & PLT Reproducibility: Four samples, five slides prepared from each, processed daily at three sites for five days.
- Data Provenance: The studies were conducted in a clinical setting using three different laboratories. The specific country of origin is not mentioned, but the context implies clinical labs. The studies appear to be prospective as samples were processed for the studies.
-
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 states that a "skilled operator trained in recognition of blood cells" identifies and verifies the suggested classification. For the comparison studies, the predicate device (DM1200) results served as the reference for comparison. While the specific number or qualifications of experts adjudicating the DM1200's results (which serve as the reference standard) are not explicitly stated, the context implies that a medically trained professional would be involved in generating and validating those results. The study design for WBC and RBC comparisons references CLSI H20-A2, which typically outlines protocols for comparison of manual differential leukocyte counts, implying that the "ground truth" (or reference standard) would have been established by trained medical technologists or pathologists according to accepted procedures.
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- The document describes a comparison study between the CellaVision® DC-1 (test device) and the CellaVision® DM1200 (reference device, K092868). The results from a "skilled operator" using the predicate device were used as the reference data. Therefore, the adjudication method for the test set ground truth (if DM1200's results are considered the ground truth equivalent) is essentially the standard workflow of the predicate device with human operator verification. There is no explicit mention of an adjudication panel for discrepancies between human observers or between the device and a human. The DC-1's proposed classifications are compared against the verified classifications from the DM1200.
-
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 MRMC comparative effectiveness study evaluating human readers with AI vs without AI assistance was presented. The study focuses on comparing the new device (DC-1, which uses CNN for pre-classification) against a predicate device (DM1200, which uses ANN for pre-classification), both of which employ AI in a human-in-the-loop workflow. Both systems are "automated cell-locating devices" where a "skilled operator" reviews and verifies the pre-classified cells. The study does not quantify the improvement of a human reader with either AI system compared to a human reader performing a completely manual differential count without any AI assistance.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- No, a standalone (algorithm only) performance study was not done or reported as part of the submission. The device is explicitly intended for "in-vitro diagnostic use in clinical laboratories" where a "skilled operator...identifies and verifies the suggested classification of each cell according to type." The device "pre-classifies" WBCs and "pre-characterizes" RBCs, but the operator's verification is integral to the intended use. The performance data for repeatability and comparability were evaluated on the "preclassified results suggested by the device" (Repeatability) or "verified WBC/RBC results from the DC-1" (Comparison), indicating the involvement of a human in the final assessment for the comparison studies.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth for the comparison studies was established by the verified results obtained from the predicate device (CellaVision® DM1200) operated by a skilled professional. This is implied to be equivalent to an expert consensus based on established laboratory practices, as the DM1200 is also a device requiring human verification. For repeatability and reproducibility studies, "preclassified results suggested by the device" or "verified data" were used, again implying that the 'ground truth' for evaluating the DC-1's consistency relies on its own outputs, or validated outputs, rather than an independent expert consensus on raw slides.
-
The sample size for the training set:
- The document does not specify the sample size used for training the Convolutional Neural Networks (CNN) for the CellaVision® DC-1. It only mentions that CNNs are used for preclassification and precharacterization.
-
How the ground truth for the training set was established:
- The document does not specify how the ground truth for the training set was established. It only states that the CNNs are "trained to distinguish between classes of white blood cells."
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
October 16, 2020
CellaVision AB % Jinjie Hu President and Principle Consultant Axteria BioMed Consulting Inc. 8040 Cobble Creek Circle Potomac, Maryland 20854
Re: K200595
Trade/Device Name: CellaVision DC-1, CellaVision DC-1 PPA Regulation Number: 21 CFR 864.5260 Regulation Name: Automated Cell-Locating Device Regulatory Class: Class II Product Code: JOY Dated: September 19, 2019 Received: March 6, 2020
Dear Jinjie Hu:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
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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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Takeesha Taylor-Bell Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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| DEPARTMENT OF HEALTH AND HUMAN SERVICES | Form Approved: OMB No. 0910-0120 |
|---|---|
| Food and Drug Administration | Expiration Date: 06/30/2020 |
| Indications for Use | See PRA Statement below. |
| 510(k) Number (if known) | K200595 |
|---|---|
| Device Name | CellaVision® DC-1 |
| Indications for Use (Describe) |
Intended use of CellaVision® DC-1
CellaVision® DC-1 is an automated cell-locating device intended for in-vitro diagnostic
use in clinical laboratories.
CellaVision® DC-1 is intended to be used by operators, trained in the use of the device.
Intended use of the Peripheral Blood Application
The Peripheral Blood Application is intended for differential count of white blood cells
(WBC), characterization of red blood cell (RBC) morphology and platelet estimation.
The CellaVision® DC-1 with the Peripheral Blood Application automatically locates
blood cells on peripheral blood (PB) smears. The application presents images of the
blood cells for review. A skilled operator trained in recognition of blood cells, identifies
and verifies the suggested classification of each cell according to type.
| 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) |
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510(k) Summary 5
General Information 5.1
| Submitter: | CellaVision ABMobilvägen 12SE-223 62 LundSwedenPhone: +46 46 460 16 00 |
|---|---|
| Contact person: | Jinjie Hu, PhDAxteria BioMed Consulting Inc.8040 Cobble Creek CirclePotomac, MD 20854,USATel:+1 (301) 814 4985Email: jinjiehu@axteriabiomed.com |
| Contact person: | Karin HannanderCellaVision ABClinical Affairs ManagerTel: +46 46 460 16 39 |
- Date Prepared: March 06, 2020
Purpose of Submission: To obtain a substantial equivalence for the CellaVision® DC-1 device.
Email: Karin.Hannander@cellavision.se
5.2 Measurand
White Blood Cells (WBC), Red Blood Cells (RBC) and Platelets (PLT).
5.3 Device
| Proprietary Name of the device: | CellaVision® DC-1andCellaVision® DC-1 PPA |
|---|---|
| Classification name: | Automated cell-locating device |
| Regulation number: | 21 CFR 864.5260 |
| Classification Name and Reference: | Class II |
| Device product Code: | JOY |
| Panel: | Hematology |
Intended use/Indication for use 5.4
CellaVision® DC-1 is an automated cell-locating device intended for in-vitro diagnostic use in clinical laboratories.
CellaVision® DC-1 is intended to be used by operators, trained in the use of the device.
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Intended use of the Peripheral Blood Application 5.5
The CellaVision Peripheral Blood Application is intended for differential count of white blood cells (WBC), characterization of red blood cell (RBC) morphology and platelet estimation. The CellaVision® DC-1 with the Peripheral Blood Application automatically locates blood cells on peripheral blood (PB) smears. The application presents images of the blood cells for review. A skilled operator trained in recognition of blood cells, identifies and verifies the suggested classification of each cell according to type.
Device Description 5.6
The CellaVision® DC-1 is an automated cell-locating device intended for in-vitro diagnostic use. CellaVision® DC-1 automatically locates and presents images of blood cells found on peripheral blood smears. The operator identifies and verifies the suggested classification of each cell according to type. CellaVision® DC-1 is intended to be used by skilled operators, trained in the use of the device and in recognition of blood cells
The CellaVision® DC-1 consists of a built-in PC with a Solid-State Disc (SSD) containing CellaVision DM Software (CDMS), a high-power magnification microscope with a LED illumination, an XY stage, a proprietary camera with firmware, built-in motor- and illumination LED controller, a casing and an external power supply. It is capable of handling one slide at a time.
The CellaVision® DC-1 can preclassify WBCs and precharacterize RBCs by use of artificial intelligence. For the larger system (DM1200), preclassification and precharacterization are performed using the Artificial Neural Network (ANN). For the CellaVision® DC-1 Convolutional Neural Networks (CNN) are used instead of ANN. The results from the clinical performance evaluations shows that the two systems (CellaVision® DC-1, tested device and CellaVision® DM1200, predicate device) have similar performance when preclassifying WBCs and precharacterizing RBCs using to the two different network types.
The CellaVision® DC-1 is for prescription use only.
5.6.1 Physical Properties of the CellaVision® DC-1
Weight: 11kg (24lb) Width: 280mm (11.0 inches) Depth: 390mm (15.4 inches) Height: 370 mm (14.6 inches)
5.6.2 Components of the CellaVision® DC-1
Computer module (integrated) Motorized microscope Digital color camera Control unit Casing Database
5.6.3 Consumables Required to produce blood smears to be used on CellaVision® DC-1
Romanowsky stain (May Grünwald Giemsa (MGG), Wriqht Giemsa (WG) or Wright (W) staining) Slides
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EDTA sample tube (K2EDTA or K3EDTA)
Automatic slide maker-stainer, or stain slides manually
5.6.4 Specimen identification
Peripheral blood samples typically flagged by a cell-counter indicating an abnormal morphology.
5.6.5 Anticoagulant
All samples used in the analytical and clinical studies were collected using K3EDTA as the anticoagulant. The protocols used in these studies state that both K₂EDTA are acceptable to use.
Studies [1, 2] have confirmed the equivalence between the two anticoagulants and that any difference between the two anticoagulants are minimal and unlikely to be of any clinical significance. Furthermore, the recognized CLSI standard [3] no longer defines K₂EDTA and K3EDTA as separate EDTA options (recognition number 7-221).
It is concluded that, based on available scientific literature that any differences between results obtained with blood collected in K5EDTA tubes vs blood collected in K2EDTA are minimal and unlikely to be of any clinical significance. ¹
5.6.6 Calibration
CellaVision recommends that calibration is performed once a year by a service engineer.
5.6.7 Quality control
5.6.7.1 Self-Test
The CellaVision® DC-1 analyzer performs self-tests during startup of the software, and at certain points during the operation of the analyzer. When the software starts, the analyzer is checked before the user can start analyzing. During this phase, both the hardware and the software components are tested for anomalies, as well as various requirements for the operation of the analyzer. If the LIS communication is enabled, the program will also check the connection to the LIS.
The communication with, and response of the hardware, is tested continuously during the operation of the analyzer, and a message will inform the user if an error occurs during slide processing or other operations on the analyzer.
5.6.7.2 Cell Location Test
A cell location test shall be run at least once a day and after any changes in the staining procedure or the staining solutions for quality control. Cell location slides are prepared and processed by the customer from a freshly stained slide from a blood sample with a WBC
1 List of references:
[1] Lab Hematol. 1998; 4:17-20. "Performance of K2EDTA- vs K3EDTA-collected blood specimens on various hematology analyzers"
[2] Lab Hematol. 2003; 9 (1):10-4. "Comparison of glass K3EDTA versus plastic K2EDTA blood-drawing tubes for complete blood counts, reticulocyte counts, and white blood cell differentials." Van Cott EM et al.
[3] CLSI GP39-A6 (former CLSI H01-A6) "Tubes and Additives for Venous and Capillary Blood Specimen Collection; Approved Standard - Sixth Edition."
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count within the normal range. The cell location test verifies that the quality of the slide preparation process is good enough to allow the analyzer to locate the cells needed for the analysis. It also verifies the analyzer's ability to locate cells. More details on the cell location test can be found in the CellaVision® DC-1 Instructions for Use.
5.6.8 Principle of operation
From a peripheral blood sample, typically flagged by a cell-counter indicating an abnormal morpholoqy, a thin blood film is wedged on a glass slide (a blood smear). The blood smear is then stained with Romanowsky stain. The system uses stained microscope slides from EDTAanticoaqulated whole blood.
The operator enters the order ID for the slide, either manually or using an optional barcode reader. If a Laboratory Information System (LIS) is used, the device automatically fetches order data for the sample from the LIS.
The operator places the slide in the loading tray of the device and closes the input hatch. The device automatically moves the slide under the microscope.
Starting at 33 mm from the edge of the slide, the device looks for a monolayer in the smear. Once a monolayer is found, the device scans the monolayer in a battlement pattern. While doing this, the device locates any WBCs and stores high quality images of each located WBC. The device also locates and stores an image of a part of the RBC monolayer. When enough WBCs and the image of the RBC monolayer have been captured, the analyzer moves the slide back to the loading tray.
The device software pre-classifies each located WBC. It also precharacterizes the RBC morphology based on the image of the RBC monolayer. By using the overview image, the operator can calculate or estimate the level of PLTs. These preliminary results, that is, the preclassifications, precharacterization and PLT levels are then stored in a database.
A skilled operator, trained in the use of the software and in recognition of blood cells, then opens the order to review and verify (or modify) the preliminary results. The review can be done either at the device or using the CellaVision Remote Review Software (CRRS).
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Table 5:1 Parameters reported for CellaVision® DC-1
| Parameter | Abbreviation |
|---|---|
| White blood cells | WBC |
| Red blood cells | RBC |
| Platelet | PLT |
Substantial equivalence information 5.7
5.7.1 Technological Characteristics Comparison with Predicate
Like the predicate device, CellaVision® DC-1 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 verify 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, CellaVision®DC-1 presents an overview image from which it is possible to characterize red blood cells regarding size, shape and color and count PLTs.
Principle of operation/comparison with predicate device 5.8
The method requires a skilled operator to review the images of the cells as does the predicate device. See attached substantial equivalence comparisons (Table 5:2).
| Characteristic | CellaVision® DC-1 | CellaVision® DM1200K092868 |
|---|---|---|
| Intended use | CellaVision® DC-1 is an automatedcell-locating device intended for in-vitro diagnostic use in clinicallaboratories.CellaVision® DC-1 is intended to beused by operators, trained in theuse of the device.Peripheral Blood Application:The CellaVision Peripheral BloodApplication is intended fordifferential count of white bloodcells (WBC), characterization of redblood cell (RBC) morphology andplatelet estimation.The CellaVision® DC-1 with thePeripheral Blood Applicationautomatically locates blood cells onperipheral blood (PB) smears. Theapplication presents images of theblood cells for review. A skilledoperator trained in recognition ofblood cells, identifies and verifies | DM1200 is an automated cell-locating device.DM1200 automatically locatesand presents images of bloodcells on peripheral bloodsmears.The operator identifies andverifies the suggestedclassification of each cellaccording to type.DM1200 is intended to be usedby skilled operators, trained inthe use of the device and inrecognition of blood cells. |
| Characteristic | CellaVision® DC-1 | CellaVision® DM1200K092868 |
| the suggested classification of eachcell according to type. | ||
| Intended usepopulation | The intended use population ispatients whose blood samples havebeen flagged as abnormal by anautomated cell counter. | Same |
| Analytes | Automated cell-locating device forcell-location and identification ofRBC, WBC or platelets for in-vitrouse.Verification of results by humanoperator. | Same |
| Light source | LED (Light Emitting Diode) | Same |
| Classificationsoftware | CellaVision® DM Software includingPeripheral blood application(version 7.0). | CellaVision® DM Softwareincluding Peripheral bloodapplication (version 6.0). |
| Sample type | Stained blood film on glass slidesof peripheral whole blood. | Same |
| Samplepreparation | Romanowsky stain | Same |
| Analysistechnique | White blood cells:Cells are located/counted bymoving according to thebattlement track pattern. Cellimages are analyzed using artificialintelligence trained to distinguishbetween classes of white bloodcells.The cell images are preclassifiedand the operator verifies thesuggested classification byaccepting or reclassifying the whiteblood cells.Red blood cells:The device presents an overviewimage.The cell images areprecharacterized and the operatorverifies or re-characterizes red | Same |
| Characteristic | CellaVision® DC-1 | CellaVision® DM1200K092868 |
| blood cell morphology from theimage.Platelets:The device presents an overviewimage.The operator manually counts andestimates the plateletconcentration from the overviewimage according to a standardizedprocedure. | ||
| Optical means formagnifyingimages of whiteblood cells forobservation andinterpretation | Individual white blood cells aremagnified and imaged on a camerasensor by a microscope. Thecamera sensor produces images ona screen for view and interpretation(cell class verification). | Same |
| Viewing of whiteblood cell images | Individual located white blood cellsare presented in an organizedmanner and observed on a screen. | Same |
| Classification ofwhite blood cells | White blood cells are pre-classifiedand presented to the operator. Tocomplete the differential, theoperator needs to verify that alllocated WBCs are correctlyclassified. All cells must beclassified and verified before theorder can be signed. | Same |
| Characterizationof the red bloodcell morphology | The device pre-characterizes theRBC morphology based on theoverview image of the RBCmonolayer, followed by theoperator's verification ormodification of the suggestedresults. | Same |
| Estimating theplatelet level | From an overview imagecorresponding to eight high powerfields the platelet level is estimated. | Same |
| Imageinterpretationrequirements | A skilled operator is required todifferentiate and finally modifyand/or confirm thepreclassification/characterization ofthe located blood cells. | Same |
| Informationtransfer from | The system can interact with alaboratory information system (LIS). | Same |
| Characteristic | CellaVision® DC-1 | CellaVision® DM1200K092868 |
| instrument toPrinter or network | The system will retrieve order datafrom the LIS and send results backto the LIS. | Same |
| Result format | The differential proportional countis normally based on 100 whiteblood cells. The number of WBCscan be modified if required. Theresult can be presented as anabsolute number or as % of totalnumber of WBCs. The result of RBCcharacterization is presented as agrading for each morphology. | Same |
| Technologicalcharacteristics | The system locates white bloodcells, stores digital images of thecells and suggests a cell class foreach white blood cell to aidoperators in performing the whiteblood cell differential procedure.The system captures an overviewimage of the RBC monolayer forRBC characterization.The operator estimates the plateletconcentration using the overviewimage. | Same |
| Operatorscompetence | The operator is trained in therecognition of blood cells and inthe use of the device. | Same |
| Decision support | The device includes white bloodcell reference cells. The operatorcan add his/her own reference cells. | Same |
| Calibration | Recommended calibration once ayear by a service engineer | Same |
Table 5:2 Comparison with Predicate Device: similarities
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Table 5:3 Comparison with Predicate Device: differences
| Characteristic | CellaVision® DC-1 | CellaVision® DM1200K092868 |
|---|---|---|
| Major parts ofthe system | • Computer module (integrated)• Motorized microscope• Digital color camera• XY stage• Control unit (integrated incamera)• Casing• Database | • System computer (stand- alone)• Motorized microscope• Digital color camera• Robot gripper unit• Control unit• Casing• Database• Immersion oil unit |
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| Characteristic | CellaVision® DC-1 | CellaVision® DM1200K092868 |
|---|---|---|
| • Barcode reader | ||
| Neural network | Neural network of convolutionaltype. | Artificial neural network ofmultiple perception type. |
| Loadingcapacity | 1 slide | 12 slides |
| Immersion oilapplication | Manual application | Automatic application |
5.9 Brief discussion of clinical tests supporting a determination of substantial equivalence
Clinical evaluations have been performed to confirm equivalence with the predicate method (DM1200) for differentiation of WBCs, precharaterization of RBCs and estimation of PLTs. In the following sections CellaVision® DC-1 and CellaVision® DM1200 will be denominated DC-1 and DM1200.
5.9.1 Performance data
The following performance data were provided in support of the substantial equivalence determination.
5.10 Electromagnetic compatibility (EMC)
EMC testing was conducted on the DC-1 and Power supply ATS090-P120. The test showed that the DC-1 is in conformity with IEC 61010-1:2010 and IEC 61010-2-101:2015.
5.11 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.
5.12 Analytical Performance: Precision, Repeatability
The repeatability studies were conducted in a clinical setting using three different laboratories. The study outline for the three repeatability studies was a so-called 20 x 2 x 2 single-site repeatability study and was based on CLSI EP05-A3 (Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition).
5.12.1 WBC Repeatability
Five samples at each of the sites were selected for the study. All slides were processed on the DC-1 according to the study outline which was a so-called 20 x 2 x 2 single-site repeatability study (total of 80 runs/sample). The evaluation was performed on the preclassified results suggested by the device. The proportional cell count in percent for each cell class was used to estimate total variance and variance components for repeatability (within-run, between-run, between-day and within laboratory) by an ANOVA. All tests except repeatability and within
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laboratory precision on three occasions met acceptance criteria. The three samples all displayed variation in mean values between slide 1 and 2 for the specific cell types, resulting in a variation slightly above acceptance criteria.
The overall results from the WBC repeatability evaluation of the DC-1 at all three sites were successful.
5.12.2 RBC Repeatability
Five samples at each of the sites were selected for the study. All slides were processed on the DC-1 according to the study outline which was a so-called 20 x 2 x 2 sinqle-site repeatability study (total of 80 runs/sample). The evaluation was performed on the precharacterized results suggested by the device. Repeatability in terms of grade (0, 1, 2 or 3) for each morphological characteristic was evaluated. The most prevalent grade reported was evaluated, and the agreement (percentage of runs reporting the grade) was calculated for each morphology. The agreement was evaluated for each slide and run (1st and 200 daily run, respectively), as well as for each sample. One sample displayed variation in mean value between slide 1 and 2 for the specific cell type, resulting in a variation above acceptance criteria.
The overall results from the RBC repeatability evaluation of the DC-1 at all three sites were successful.
5.12.3 PLT Repeatability
Four samples at each of the sites were selected for the study. All slides were processed on the DC-1 according to the study outline which was a so-called 20 x 2 x 2 single-site repeatability study (total of 80 runs/sample). For each PLT level (significantly decreased, decreased, normal or increased) the agreement (percentage of runs reporting the actual PLT level) was evaluated. The agreement was evaluated for each slide and run (14t and 2nd daily run, respectively) as well as for each sample.
The repeatability of PLT analysis met the acceptance criterion in all samples at all three sites.
5.13 Analytical Performance: Precision, Reproducibility
The reproducibility study was conducted in a clinical setting using three different laboratories. The study outline was a so-called 3 x 5 x 5 multi-site reproducibility study and was based on CLSI EP05-A3 (Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition).
5.13.1 WBC Reproducibility
Five samples were included in the study. Five slides were prepared from each sample and processed every day at each of three study sites for five days (a 3 x 5 x 5 study). The reproducibility analysis was performed on verified data. The proportional cell count in percent for each cell class was used to estimate total variance components for reproducibility by an ANOVA based on CLSI EP05-A3. Evaluation was performed for each cell class per sample as well as per sample and site.
The overall results from the reproducibility evaluation of the DC-1 are considered to be successful.
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5.13.2 RBC Reproducibility
Four samples were included in the study. Five slides were prepared from each sample and processed every day at each of three study sites for five days (a 3 x 5 x 5 study). The reproducibility analysis was performed on verified data. Reproducibility in terms of grade (0, 1, 2 or 3) for each morphological characteristic was evaluated. The most prevalent grade reported was evaluated, and the agreement (percentage of runs reporting the grade) was calculated. The agreement was evaluated for each morphology per sample as well as per sample and site.
The overall results from the reproducibility evaluation of the DC-1 are considered to be successful.
5.13.3 PLT Reproducibility
Four samples were included in the study. Five slides were prepared from each sample and processed every day at each of three study sites for five days (a 3 x 5 x 5 study). The operator used the overview image to count the platelets per grid square.
For each PLT level (significantly decreased, normal or increased) the agreement (percentage of runs reporting the most prevalent level) was calculated for each sample as well as for each sample and site. The reproducibility of the PLT count met the acceptance criterion in all samples.
The overall results from the reproducibility evaluation of the DC-1 are considered to be successful.
5.13.4 Linearity
Not applicable
5.13.5 Carryover
Not applicable
5.13.6 Interfering substance
Not applicable
5.14 Clinical Performance: Method, Comparison
The comparison studies were conducted at three different laboratories for each analyte (WBC, RBC and PLT).
Comparison studies were conducted comparing the DC-1 (test device) with the DM1200 (reference device) for each of the cell types (WBC, RBC and PLT).
Three comparison studies have been performed for each of the cell types (3 for WBC, 3 for RBC and 3 for PLT). The WBC and RBC studies were based on CLSI H20-A2 (RBC, only applicable parts).
5.14.1 WBC Comparison
ln total 598 samples (1196 slides, A and B slide) were analyzed on both the DM1200 and on the DC-1 across the three sites. The verified WBC results from the DC-1 were compared to the corresponding results from the DM1200. Accuracy as well as Positive (PPA), Negative (NPA) and Overall Agreement (OA) were determined.
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5.14.1.1 Distribution and Morphology
PPA, NPA and OA were calculated for the distributional and morphological results separately.
Table 5:4 Combined results all three sites
| Group/Site | Comparison | Results % |
|---|---|---|
| Distribution | OA | 89,8% |
| PPA | 89,2% | |
| NPA | 90,4% | |
| Morphology | OA | 91,3% |
| PPA | 88,6% | |
| NPA | 92.5% |
5.14.1.2 WBC Accuracy
Accuracy between WBC analysis results from the DC-1 compared to the DM1200 was determined using linear regression. The mean differential counts for individual cell types with a normal level of >5% were analyzed. The slope of the regression line when compared with the reference method should be within 0.8-1.2 with an intercept within ±0.2. The accuracy evaluations were successful in all studies and shows no systematic difference between the DC-1 and the DM1200.
The accuracy agreement for the applicable WBCs (Segmented Neutrophils, Lymphocytes, Eosinophils and Monocytes) were all within the acceptance criteria.
5.14.2 RBC Comparison
In total 586 samples were analyzed on both the DM1200 and on the DC-1across the three sites. The verified RBC results from the DC-1 were compared to the corresponding results from the DM1200.
PPA, NPA and OA with two-sided 95% confidence intervals, comparing the DC-1 results with the DM1200 results, were calculated. The results were assumed to be normally distributed and calculations of 95% confidence intervals have been performed as described in EP-12-A2.
| Group | Comparison | Result(95% CI LL-UL) |
|---|---|---|
| Color | OA | 79,9%(76,4%-82,9%) |
| PPA | 87,8%(82,3%-91,8%) | |
| NPA | 76,3%(71,9%-80,2%) | |
| Size | OA | 88,2%(85,3%-90,6%) |
| PPA | 89,8%(86,3%-92,2%) | |
| NPA | 84,8%(79,0%-89,2%) | |
| Shape | OA | 85,2% |
Table 5:5 Combined results all three sites
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| (82,0%-87,8%) | |
|---|---|
| PPA | 87,3%(82,3%-91,0%) |
| NPA | 83,8%(79,6%-87,3%) |
5.14.3 PLT Comparison
In total 598 samples were analyzed on both the DM1200 and on the DC-1across the three sites.
The agreement between the two devices on PLT level was evaluated by summarizing the results as outlined in
Table 5:6 below and by calculating the Cohen's Kappa coefficient.
Each level was assigned a number:
- 1 = Sign. Decreased
- 2 = Decreased
- 3 = Normal
- 4 = Increased
| Table 5:6 Agreement per sample | |
|---|---|
| -------------------------------- | -- |
| DC-1 | DM1200 | ||||
|---|---|---|---|---|---|
| Level 1 | Level 2 | Level 3 | Level 4 | Total | |
| Level 1 | 140 | 16 | 0 | 0 | 156 |
| Level 2 | 6 | 135 | 13 | 0 | 154 |
| Level 3 | 0 | 10 | 173 | 10 | 193 |
| Level 4 | 0 | 0 | 17 | 78 | 95 |
| Total | 146 | 161 | 203 | 88 | 598* |
*All samples were collected based on the results from cell counters.
Table 5:7 Cohen's Kappa coefficient calculated using Medcalc®
| Weighted Kappa* | 0,89405 |
|---|---|
| Standard error | 0,01196 |
| 95% Cl | 0,87062 to 0,91748 |
In all three studies the Cohen's Kappa coefficient met the acceptance criterion of ≥0,6.
The conclusion of the evaluations of the PLT estimation analysis is that the agreement requirement is fulfilled.
5.15 Proposed labeling
The labeling satisfies the requirement of 21 CDR Part 809.subpart B.
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5.16 Conclusion
The CellaVision® DC-1 analyzer has the same intended use as the predicate device, the CellaVision® DM1200 analyzer cleared in K092868. They are quantitative, automated hematology analyzers for In Vitro Diagnostic Use in clinical laboratories. These analyzers may be used with K2 EDTA or K3 EDTA whole blood. Both analyzers are only to be used by trained medical professionals to identify abnormal parameters of WBC, RBC and PLT. The performance studies of the CellaVision® DC-1 analyzer were conducted per the study protocols agreed by FDA in pre-submission (Q171293) covering all cell types and morphologies that the analyzer is intended to identify. For WBC, the samples studied covered both normal and abnormal levels for band neutrophils, segmented neutrophils, eosinophils, basophils, lymphocytes, and monocytes. Samples with abnormal concentrations of promyelocytes, myelocytes, metamyelocytes, blast cells, variant lymphocytes, plasma cells and NRBC were also included in the study. For RBC, the samples studied covered all morphological characteristics. For PLT, four samples covering the predefined levels were included. The performance comparison study results demonstrated that the CellaVision® DC-1 analyzer is substantially equivalent to the predicate device, the CellaVision® DM1200 analyzer and the few differences do not raise new questions of the safety and effectiveness.
The overall results from both the clinical and analytical evaluations concluded that the studies performed for WBC, RBC and PLT on the CellaVision® DC-1 are considered to be successful. No adverse events were reported from any of the studies.
§ 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).