(89 days)
Yes
The device description explicitly mentions the use of "deterministic artificial neural networks (ANNs)" for pre-characterizing red blood cells.
No
The device is an in-vitro diagnostic device used to locate and present images of blood cells for classification, not to treat a condition or ailment.
Yes
The device is intended for "in-vitro diagnostic use" and "automatically locates and presents images of blood cells on peripheral blood smears" to aid in the "classification of each cell according to type," which is a diagnostic function. It also aims to "pre-characterize the morphology of the red blood cells in a sample based on abnormal color, size, and shape," and is used for "blood samples that have been flagged as abnormal by an automated cell counter."
No
The device description explicitly states it is an "Advanced RBC Application" that is used with "DM Systems" (CellaVision DM96 and DM1200), which are described as "automated cell-locating devices." This indicates the device includes hardware components for image acquisition and processing, not just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "The CellaVision DM1200 with the Advanced RBC Application is an automated cell-locating device, intended for in-vitro diagnostic use." and "The CellaVision DM96 with the Advanced RBC Application is an automated cell-locating device, intended for in-vitro diagnostic use."
- Purpose: The device is used to analyze blood cells on peripheral blood smears, which are biological samples taken from the human body. This analysis is performed in vitro (outside the body) to provide information for diagnostic purposes.
- Clinical Context: The device is intended for use with blood samples flagged as abnormal by an automated cell counter and is used by skilled operators in a laboratory setting, indicating its role in the diagnostic workflow.
- Performance Studies: The document describes clinical evaluation studies comparing the device's performance to manual microscopy and an automated cell counter, which are typical for IVD devices seeking regulatory clearance.
All these points strongly support the classification of this device as an In Vitro Diagnostic.
No
The letter does not explicitly state that the FDA has reviewed and approved or cleared a Predetermined Change Control Plan (PCCP) for this specific device.
Intended Use / Indications for 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.
Product codes
JOY
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.
Mentions image processing
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.
Mentions AI, DNN, or ML
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.
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
skilled operators, trained in the use of the device and in recognition of blood cells.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Reproducibility study:
- 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.
- Based on the CLSI EP05-A3 guidance document.
- From each sample, 3 slides were prepared.
- Slides were run at each site 2 times a day for 5 days.
- Grading reproducibility calculated by determining the relation between the occurrence of true grade and the total number of runs.
- Proportional cell count in percent for each morphological characteristic 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.
- Results met predefined acceptance criteria.
Repeatability study:
- 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.
- 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.
- Grading agreement 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.
- Proportional cell count in percent for each morphological characteristic used to estimate total variance and variance components for repeatability (i.e. within-run), between-run, and between-day based on CLSI EP05-A3.
- Results met predefined acceptance criteria.
Clinical Evaluation:
- Comparison study 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), an automated cell counter (non-reference standard) was used as manual microscopy is highly difficult, time consuming and impractical.
- Study performed based on the approved guidance document CLSI H20-A2.
- Samples were collected and tested for RBC characterization on DM96 and DM1200 at different laboratories.
- Samples included blood samples, collected in accordance with the target patient population, i.e., from samples flagged as abnormal by an automated cell counter.
- Objective was to show that the RBC characterization results using the CellaVision Advanced RBC Application are equivalent with results achieved using the comparative method.
- Comparison study demonstrated 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.
- Study demonstrated that the sensitivity and specificity for the individual morphological characteristics fulfilled the target limits.
Conclusion: 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.
Key Metrics
PPA (Positive Percent Agreement), NPA (Negative Percent Agreement), efficiency, sensitivity, and specificity.
Predicate Device(s)
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).
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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).
0
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
1
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
2
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) | ||||
|---|---|---|---|---|
| ```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.
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*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
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FORM FDA 3881 (8/14)
Page of
PSC Publishing Services (301) 443-6740 EF
3
510(k) Summary
This 510(k) summary is being submitted in accordance with the requirements of 21 CFR807.92.
510(k) Number
. 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
4
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.
5
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
process | DM Systems | DM Systems with Advanced
RBC Application |
|---------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | Manual method for cell-
locating and identification of
red blood cells from
peripheral blood smears.
Verification of results by
skilled human operator. | DM Systems is an automated
cell-locating device, intended
for in-vitro diagnostic use.
DM Systems 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.
DM Systems is intended to be
used by skilled operators,
trained in the use of the
device and in recognition of
blood cells. | DM Systems with the
Advanced RBC Application is
an automated cell-locating
device, intended for in-vitro
diagnostic use.
DM Systems 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.
DM Systems with the
Advanced RBC Application is
intended for blood samples
that have been flagged as
abnormal by an automated
cell counter.
DM Systems 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. |
| Intended use
population | The intended use population
is patients whose blood
samples have been flagged
as abnormal by an automated
cell counter. | The intended use population
is patients whose blood
samples have been flagged
as abnormal by an automated
cell counter. | The intended use population
is patients whose blood
samples have been flagged
as abnormal by an automated
cell counter. |
| Specimen type | Peripheral blood. | Peripheral blood. | Peripheral blood. |
| Sample
preparation | Romanowsky stained blood
film on glass slides of
peripheral whole blood. | Romanowsky stained blood
film on glass slides of
peripheral whole blood. | Romanowsky stained blood
film on glass slides of
peripheral whole blood. |
| Characteristic | Manual light microscopic
process | DM Systems | DM Systems with Advanced
RBC Application |
| Analysis
technique | The examiners characterize
red blood cell morphology
from an overview based on
size, color, shape and
inclusion. | The device presents an
overview image.
The cell images are pre-
characterized into 6 different
morphological characteristics
based on size color and
shape using segmentation,
feature calculation and
classification (decision tree): | The device presents an
overview image.
The cell images are pre-
characterized into 21 different
morphological characteristics
based on size, color, shape
and inclusion using
segmentation, feature
calculation and the
deterministic artificial neural
networks (ANNs) trained to
distinguish between
morphology characteristics of
red blood cells. |
| Pre-
characteriztion | N/A | The cell images are pre-
characterized into the
following morphologies:
-
Polychromatic cells;
-
Hypochromatic cells;
-
Anisocytosis;
-
Microcytes;
-
Macrocytes; and
-
Poikilocytosis. | The cell images are pre-
characterized into the
following 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-defined
characteristics | N/A | The operator can further
characterize into 10 user-
defined characteristics. | The operator can further
characterize into 10 user-
defined characteristics. |
| Verification of
results | N/A | The operator verifies the
suggested morphological
characteristics by accepting
or re-characterizing. | The operator verifies the
suggested morphological
characteristics by accepting
or re-characterizing. |
| 510(k) numbers | 510(k) exempt (864.3600) | K033840 (DM96) | N/A |
6
PERFORMANCE DATA VII.
The following performance data were provided in support of the substantial equivalence determination.
7
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
8
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.