(122 days)
The VEGA™ Hematology Analyzer is a quantitative, automated in vitro diagnostic analyzer capable of performing the following twenty six (26) hematological parameters: white blood cells (leukocytes) -WBC, red blood cells (erythrocytes) -RBC, hemoglobin -HGB, hematocrit -HCT, mean corpuscular volume -MCV, mean corpuscular hemoglobin -MCH, mean corpuscular hemoglobin concentration -MCHC, red blood cell distribution width -RDW, platelets -PLT, plateletcrit -PCT, platelet distribution width -PDW, mean platelet volume -MPV, lymphocyte (number) -LYM#, lymphocyte (percent of WBC) -LYM%, monocyte (number) -MON#, monocyte (percent of WBC) -MON%, basophil (number) -BAS#, basophil (percent of WBC) -BAS%, neutrophil (number) -NEU#, neutrophil (percent of WBC) -NEU%, eosinophil (number) -EOS#, eosinophil (percent of WBC) -EOS%, Atypical Lymphocyte (number) -ALY#, Atypical Lymphocyte (percent of lymphocyte number) -ALY%, Large Immature cell (number) -LIC#, Large Immature cell (percent of WBC) -LIC%.
Only twenty (20) parameter printout will be made available for diagnostic use in the United States (eliminating PCT, PDW, ALY%, ALY#, LIC%, LIC#).
The VEGA™ Hematology Analyzer is a quantitative, automated in vitro diagnostic analyzer capable of performing twenty six (26) hematological parameters. It utilizes five (5) different reagents: VEGADIL™, VEGALYSE™, VEGACLEAN™, EOSINOFIX™, and BASOLYSE™. The counting principle for WBC, RBC, and PLT is based on impedance variation. HGB is measured by spectrophotometry. HCT is measured by a specialized electronic device that adds pulse heights. MCH, MCHC, and MCV are calculated indices. RDW is a coefficient of variation of RBC distribution. MPV is a platelet index. Leukocyte differential counts are performed using cytochemistry with Eosinofix™ reagent, impedance to measure volume, and optical transmission measurement to obtain information on the internal structure of the cells.
Here's an analysis of the provided text, focusing on acceptance criteria and the study used to demonstrate them for the VEGA™ Hematology Analyzer.
The document describes the VEGA™ Hematology Analyzer and its performance characteristics through clinical studies conducted at three university hospital sites. The studies aimed to demonstrate the precision and accuracy of the device.
1. Table of Acceptance Criteria and Reported Device Performance
Note: The document does not explicitly state "acceptance criteria" but presents performance metrics (reproducibility and linearity claims) that serve as de-facto acceptance criteria against the reported actual performance. For accuracy, the R² values indicate correlation with predicate devices, which can be interpreted as demonstrating acceptable performance against established methods.
| Parameter | Acceptance Criteria (Stated Claim/Target) | Reported Device Performance (Worst Case Across Sites/Parameters, where applicable) |
|---|---|---|
| Reproducibility (CV%) | ||
| WBC | < 2.0% (at 10 10³/mm³) | < 2.0% |
| RBC | < 2.0% (at 5 10⁶/mm³) | < 2.0% |
| HGB | < 1.0% (at 15.0 g/dL) | < 1.0% |
| HCT | < 2.0% (at 45.0%) | < 2.0% |
| MCV | < 1.5% | < 1.5% |
| MCH | < 1.5% | < 1.5% |
| MCHC | < 1.5% | < 1.5% |
| RDW | < 3.5% | < 3.5% |
| PLT | < 5.0% (at 300 10³/mm³) | < 5.0% |
| MPV | < 5.0% | < 5.0% |
| LYM% | < 5.0% (at 30%) | < 5.0% |
| LYM# | < 5.0% (at 2.1 10³/mm³) | < 5.0% |
| MON% | < 15.0% (at 5%) | < 15.0% |
| MON# | < 15.0% (at 0.5 10³/mm³) | < 15.0% |
| NEU% | < 3.0% (at 60%) | < 3.0% |
| NEU# | < 3.0% (at 4.2 10³/mm³) | < 3.0% |
| EOS% | < 25.0% (at 3%) | < 25.0% |
| EOS# | < 25.0% (at 0.3 10³/mm³) | < 25.0% |
| BASO% | < 40.0% (at 1%) | < 40.0% |
| BASO# | < 40.0% (at 0.1 10³/mm³) | < 40.0% |
| Linearity (Accuracy) | ||
| WBC | Within 0.2 x10³/mm³ or 3% of expected value | The device is described as operating within these limits. |
| RBC | Within 0.3 x10⁶/mm³ or 2% of expected value | The device is described as operating within these limits. |
| PLT | Within 10 x10³/mm³ or 5% of expected value | The device is described as operating within these limits. |
| HGB | Within 0.2 g/dL or 2% of expected value | The device is described as operating within these limits. |
| HCT | Within 3% of the expected value | The device is described as operating within these limits. |
| Carryover (Actual vs. Claim) | ||
| WBC | < 2.0% | 0.00% |
| RBC | < 0.5% | 0.00% |
| HGB | < 0.5% | 0.00% |
| HCT | < 2.0% | 0.00% |
| PLT | < 2.0% | 0.04% |
| Accuracy (Correlation with Predicate Device) (R²) | ||
| WBC (min R²) | N/A (implicit target high R²) | 0.9945 |
| RBC (min R²) | N/A | 0.9857 |
| HGB (min R²) | N/A | 0.9908 |
| HCT (min R²) | N/A | 0.9619 |
| MCV (min R²) | N/A | 0.8089 |
| MCH (min R²) | N/A | 0.9113 |
| MCHC (min R²) | N/A | 0.1484 (Notably low) |
| RDW (min R²) | N/A | 0.5457 |
| PLT (min R²) | N/A | 0.9822 |
| MPV (min R²) | N/A | 0.2286 (Notably low) |
| %LYMPH (min R²) | N/A | 0.8081 |
| %MON (min R²) | N/A | 0.3030 (Notably low) |
| %NEUT (min R²) | N/A | 0.7975 |
| %EOS (min R²) | N/A | 0.6618 |
| %BASO (min R²) | N/A | 0.2391 (Notably low) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Sample Sizes (N):
- Site 1: 190 samples
- Site 2: 238 samples
- Site 3: 216 samples
- Total samples used for accuracy: 190 + 238 + 216 = 644 samples.
- Reproducibility (within run) calculated from 20 results of the same sample.
- Data Provenance: The clinical studies were performed at three hospital university sites. The country of origin is not explicitly stated for the samples, but the sponsor is based in MONTPELLIER, FRANCE. The document implies the studies were conducted in a "typical setting" (e.g., hospital labs), suggesting real-world, clinical samples. The study design ("clinical study") and the mention of "widest distribution of normal and abnormal specimens" suggest that these were prospective collections or at least representatively selected samples rather than purely retrospective database pulls. Since it's a 510(k) submission, the data is typically considered clinical trial data, which would be prospective for this type of device validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- Number of Experts: Not explicitly stated. The document mentions "Manual differential count were performed for the samples at all three sites." This implies trained laboratory personnel, but the specific number of individuals or their "expert" qualifications (e.g., pathologist, specific experience level) are not detailed.
- Qualifications of Experts: Not explicitly stated beyond "operators of various levels of experience and educational backgrounds" for the VEGA Analyzer testing and "Manual differential count were performed... according to NCCLS guidelines H20-A" for ground truth, which implies trained medical laboratory scientists.
4. Adjudication Method for the Test Set
- Adjudication Method: Not explicitly stated. For the manual differential counts, it's mentioned they were performed according to NCCLS guidelines H20-A. These guidelines generally prescribe specific methodologies for manual counts, and any adjudication process (e.g., multiple counts, arbitration by a senior technologist/pathologist) would typically fall under those standard laboratory practices, but isn't detailed here. For the accuracy comparison (VEGA vs. predicate devices), the predicate devices themselves served as the reference for comparison, not an adjudication process among human readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- MRMC Study: No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly described. The study compared the VEGA™ Hematology Analyzer's performance against established predicate devices (TECHNICON H2®, ABBOT CELL-DYN® 3500, COULTER STKS®) and manual differential counts, which is a common approach for IVD devices. It did not involve comparing human readers' performance with and without AI assistance (as the VEGA is not an "AI" device in the modern sense of a diagnostic aid to humans, but rather an automated analyzer).
- Effect Size of Human Reader Improvement: Not applicable, as this was not an MRMC study and the device does not provide "AI assistance" for human readers in the traditional sense.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Standalone Performance: Yes, the entire clinical study described (reproducibility, linearity, carryover, accuracy against predicate devices) represents the standalone performance of the VEGA™ Hematology Analyzer as an automated system. This device is an "algorithm only" (automated analyzer) type without a human-in-the-loop component for interpreting its primary results. The reference to "operators of various levels of experience and educational backgrounds" refers to the users operating the device, not interpreting results with "human-in-the-loop" AI assistance.
7. The Type of Ground Truth Used
The ground truth used for performance evaluation was a combination of:
- Predicate Devices: For most parameters (WBC, RBC, HGB, etc.), the results from legally marketed and established hematology analyzers (TECHNICON H2®, ABBOT CELL-DYN® 3500, and COULTER STKS®) served as the reference for accuracy comparisons.
- Expert Consensus / Gold Standard Manual Methods: For differential counts, "Manual differential count were performed... according to NCCLS guidelines H20-A." These manual counts, performed by trained laboratory personnel, represent a universally accepted ground truth for leukocyte differential.
- Defined Reference Values: For reproducibility values, specific reference values (e.g., 10 10³/mm³ for WBC) were used. These would correspond to known control material values or target ranges.
8. The Sample Size for the Training Set
- Training Set Sample Size: Not specified. The document describes a 510(k) submission, which focuses on validation data (test set) for substantial equivalence. The training set for the device's internal algorithms (e.g., how it learned to classify cells or establish thresholds) is not discussed. This information is typically proprietary to the manufacturer and not required in a 510(k) summary focused on performance data.
9. How the Ground Truth for the Training Set Was Established
- Training Set Ground Truth: Not specified. As with the training set sample size, the methodologies for developing and training the internal algorithms of the VEGA™ Hematology Analyzer are not detailed in this 510(k) summary. This would have been part of the internal development and verification process by ABX.
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Image /page/0/Picture/2 description: The image shows a sequence of handwritten characters. The sequence starts with the letter 'K', followed by the number '9', and then the letter 'X'. The sequence continues with the number '6', another letter 'X', and ends with the number '33'.
Nov - 4 1996
510(k) SUMMARY
VEGA ™Hematology Analyzer
In accordance with the Safe Medical Devices Act of 1990, a 510(k) summary is provided as outlined in 21 CFR 807.92.
I. Identification of the Sponsor and Objective:
ABX
Parc Euromédecine,
rue du Caducée - BP 7290,
34184 MONTPELLIER Cédex 4 - FRANCE.
| 510(k) Submission dated | 2/7 , 1996. |
|---|---|
| Contact: | Mr. Brice Prouvé |
| Business Development Manager. | |
| phone: (33) 6714-1516/59/72 | |
| fax: (33) 6714-1517 |
II. Device Name:
Trade/Proprietary Name -VEGA™ Hematology Analyzer
| Common or Usual Name/ | Automated cell counter [864.5200] and |
|---|---|
| Classification Name - | Automated Differential Cell Counter [864.5220] |
Identification of the legally marketed device to which the 510(k) & III. sponsor claims equivalence:
TheVEGA™ Hematology Analyzer is substantially equivalent to the TECHNICON H2 ® Hematology Analyzer, the ABBOT CELL-DYN ® 3500 Hematology Analyzer and the COULTER STKS ® Hematology Analyzer.
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Description of the Device/Statement of Intended Use: IV.
The VEGA™ Hematology Analyzer is a quantitative, automated in vitro diagnostic analyzer capable of performing the following twenty six (26) hematological parameters:
| white blood cells (leukocytes) | -WBC |
|---|---|
| red blood cells (erythrocytes) | -RBC |
| hemoglobin | -HGB |
| hematocrit | -HCT |
| mean corpuscular volume | -MCV |
| mean corpuscular hemoglobin | -MCH |
| mean corpuscular hemoglobin concentration | -MCHC |
| red blood cell distribution width | -RDW |
| platelets | -PLT |
| plateletcrit | -PCT |
| platelet distribution width | -PDW |
| mean platelet volume | -MPV |
| lymphocyte (number) | -LYM# |
| lymphocyte (percent of WBC) | -LYM% |
| monocyte (number) | -MON# |
| monocyte (percent of WBC) | -MON% |
| basophil (number) | -BAS# |
| basophil (percent of WBC) | -BAS% |
| neutrophil (number) | -NEU# |
| neutrophil (percent of WBC) | -NEU% |
| eosinophil (number) | -EOS# |
| eosinophil (percent of WBC) | -EOS% |
| Atypical Lymphocyte (number) | -ALY# |
| Atypical Lymphocyte (percent of lymphocyte number) | -ALY% |
| Large Immature cell (number) | -LIC# |
| Large Immature cell (percent of WBC) | -LIC% |
The VEGA Hematology Analyzer can be programmed to printout any of the parameters here above independently.
Only twenty (20) parameter printout will be made available for diagnostic use in the United States (eliminating PCT, PDW, ALY%, ALY#, LIC%, LIC#).
The VEGA Hematology Analyzer utilizes five (5) different reagents.
| - | VEGADILTM | : | Diluant |
|---|---|---|---|
| - | VEGALYSETM | : | Lysing Agent |
| - | VEGACLEANTM | : | Cleaner |
| - | EOSINOFIXTM | : | Staining Agen |
| - | BASOLYSETM | : | Lysing Agent |
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VEGA Measurement Principles:
WBC, RBC, PLT: The counting principle is based on an impedance variation generated by the passage of cells through the calibrated micro-aperture.
HGB: A cyanmethemoglobin compound is measured by spectrophotometry through the optical part of the WBC chamber at a wavelength of 550 nanometers.
HCT: The height of the impulse generated by the passage of the cell through the micro-aperture is directly proportional to the volume of analyzed red blood cell. The HCT measurement is performed by a specialized electronic device which adds all the pulse heights.
MCH, MCHC, MCV are red blood cell indices calculated from the measured parameters.
RDW is a coefficient of variation of the RBC distribution and is expressed as a percent of the average RBC size.
MPV is a platelet indice derived from the accumulation of platelet data within the platelet population distribution.
Leukocyte Differential Counts:
The VEGA Hematology Analyzer uses the similar method counting as the Roche COBAS Argos 5 DIFF Hematology Analyzer. The VEGA Hematology Analyzer combines the use of histochemical stains, measurement of blood cell volume via optical transmission from a tungsten halogen light source to provide leukocyte differentiation. On each individual cell, three methods are aplied:
-
- Cytochemistry with the action of Eosinofix ™ reagent.
-
- Impedance to measure the volume.
-
- Optical transmission measurement to obtain information on the internal structure of the cells.
V. Summary of the technological characteristics of the new device in comparison to those of the predicate:
The intended use and measurement principles are the same for each analyzer. There are differences in operation, configuration and capabilities of each device. Algorithms and threshold discrimination of each instrument are slightly different.
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Brief discussion of the clinical and non-clinical tests relied on for a VI. determination of substantial equivalence:
Clinical studies were performed at three hospital university sites. The clinical study was designed to demonstrate the precision and accuracy of the VEGA Analyzer in a typical setting with operators of various levels of experience and educational backgrounds.
Each site used different reference instrument: Site 1 used a TECHNICON H2 ® Hematology Analyzer; Site 2 used the ABBOT CELL-DYN ® 3500 Hematology Analyzer; and Site 3 used the COULTER STKS ® Hematology Analyzer.
Manual differential count were performed for the samples at all three sites to reflect the widest distribution of normal and abnormal specimens. The cell counts were performed according to NCCLS guidelines H20-A, at all three hospital laboratories. A summary of performance data follows:
Reproducibility (within run):
Reproducibility of an instrument is measured by the coefficient of variation (CV) obtained from the calculation of 20 results of the same sample.
| Parameters | %CV | Reference Values |
|---|---|---|
| - WBC: | < 2.0% | 10 10³/mm³ |
| - RBC: | < 2.0% | 5 10⁶/mm³ |
| - HGB: | < 1.0% | 15.0 g/dL |
| - HCT: | < 2.0% | 45.0% |
| - MCV: | < 1.5% | |
| - MCH: | < 1.5% | |
| - MCHC: | < 1.5% | |
| - RDW: | < 3.5% | |
| - PLT: | < 5.0% | 300 10³/mm³ |
| - MPV: | < 5.0% | |
| - LYM%: | < 5.0% | 30% |
| - LYM #: | < 5.0% | 2.1 10³/mm³ |
| - MON%: | < 15.0% | 5% |
| - MON#: | < 15.0% | 0.5 10³/mm³ |
| - NEU%: | < 3.0% | 60% |
| - NEU#: | < 3.0% | 4.2 10³/mm³ |
| - EOS%: | < 25.0% | 3% |
| - EOS#: | < 25.0% | 0.3 10³/mm³ |
| - BASO%: | < 40.0% | 1% |
| - BASO#: | < 40.0% | 0.1 10³/mm³ |
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Linearity:
Linearity can be considered as the high and low limits for the instrument use for each parameter.
| Parameter | Range | Limits |
|---|---|---|
| WBC (103/mm3) | 0.1 - 85.0 (103/mm3) | 0.2 x103/mm3 or 3% of the expected value |
| RBC (106/mm3) | 0.5 - 8.1 (106/mm3) | 0.3 x106/mm3 or 2% of the expected value |
| PLT (103/mm3) | 10 - 1000 (103/mm3) | 10 x103/mm3 or 5% of the expected value |
| HGB (g/dL) | 2.0 - 25.0 (g/dL) | 0.2 g/dL or 2% of the expected value |
| HCT(%) | 10.0 - 70.0 (%) | 3% of the expected value |
Carryover:
| WBC | RBC | HGB | HCT | PLT | |
|---|---|---|---|---|---|
| Mean Level | 57.5 | 8.5 | 24.0 | 72.0 | 944 |
| % Carry-over actual | 0.00 | 0.00 | 0.00 | 0.00 | 0.04 |
| CV % Claim | <2.0% | <0.5% | <0.5% | <2.0% | <2.0% |
Normal Ranges:
These values were taken from the " Hematology Clinical and Laboratory Practice " Copyright 1993 by Mosby - Year Book, Inc., Editor in Chief: Rodger L. Bick, MD.
| PARAMETERS | MALE | FEMALE |
|---|---|---|
| WBC (103/mm3) | 4.5 - 11 | 4.5 - 11 |
| Lymphocytes (%) | 25 - 33 | 25 - 33 |
| Monocytes (%) | 3 - 7 | 3 - 7 |
| Neutrophils (%) | 54 - 62 | 54 - 62 |
| Eosinophils (%) | 1 - 3 | 1 - 3 |
| Basophils (%) | 0 - 0.75 | 0 - 0.75 |
| RBC (106/mm3) | 4.6 - 6.2 | 4.2 - 5.2 |
| HGB (g/dl) | 14 - 18 | 12 - 16 |
| HCT (%) | 40 - 54 | 37 - 47 |
| MCV (fL) | 80 - 96 | 80 - 96 |
| MCH (pg) | 26 - 34 | 26 - 34 |
| MCHC (g/dL) | 32 - 36 | 32 - 36 |
| RDW (%) | 12 - 16 | 12 - 14 |
| PLT(103/mm3) | 150 - 350 | 150 - 350 |
| MPV (fL) | 7 - 9 | 8 - 10 |
All parameters here above can be adapted to the lab. requirement.
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Accuracy:
| SITE 1 | SITE 2 | SITE 3 | ||||
|---|---|---|---|---|---|---|
| parameter | N | R2 | N | R2 | N | R2 |
| WBC (103/mm3) | 190 | 0.9945 | 238 | 0.9965 | 216 | 0.9975 |
| RBC (106/mm3) | 190 | 0.9873 | 238 | 0.9857 | 216 | 0.9933 |
| HGB (g/dL) | 190 | 0.9908 | 238 | 0.9947 | 216 | 0.9970 |
| HCT (%) | 190 | 0.9619 | 238 | 0.9820 | 216 | 0.9903 |
| MCV (µm3) | 190 | 0.8089 | 238 | 0.9346 | 216 | 0.9593 |
| MCH (pg) | 190 | 0.9402 | 238 | 0.9113 | 216 | 0.9646 |
| MCHC (g/dL) | 190 | 0.1484 | 238 | 0.2008 | 216 | 0.5266 |
| RDW (%) | 190 | 0.5457 | 238 | 0.8003 | 216 | 0.7450 |
| PLT (103/mm3) | 190 | 0.9822 | 238 | 0.9827 | 216 | 0.9854 |
| MPV (µm3) | 190 | 0.2286 | 238 | 0.7149 | 216 | 0.8379 |
| %LYMPH | 190 | 0.8081 | 238 | 0.9669 | 216 | 0.9919 |
| %MON | 190 | 0.3030 | 238 | 0.7280 | 216 | 0.6996 |
| %NEUT | 190 | 0.7975 | 238 | 0.9179 | 216 | 0.9829 |
| %EOS | 190 | 0.8853 | 238 | 0.6618 | 216 | 0.9558 |
| %BASO | 190 | 0.3546 | 238 | 0.3789 | 216 | 0.2391 |
| Reference Analyzers | TECHNICON H2 | CELL DYN 3500 | COULTER STKS |
VII. Conclusions:
Based on these data, the VEGA™ Hematology Analyzer is substantially equivalent to the TECHNICON H2 ® Hematology Analyzer, the ABBOT CELL-DYN ® 3500 Hematology Analyzer and the COULTER STKS ® Hematology Analyzer. for the intended use of performing a twenty parameters hematological profile of whole blood specimens.
§ 864.5220 Automated differential cell counter.
(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”