510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION

DECISION MEMORANDUM

A. 510(k) Number:

k141161

B. Purpose for Submission:

Clearance of a new device.

C. Manufacturer and Instrument Name:

Horiba ABX SAS, ABX Micros ES 60 OT and ABX Micros ES 60 CT

D. Type of Test or Tests Performed:

Quantitative test for white blood count (WBC), red blood count (RBC), hemoglobin (HGB),
hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH),
mean corpuscular hemoglobin concentration (MCHC), platelets (PLT), lymphocyte
(LYM)%/#, monocyte (MON)%/#, granulocytes (GRA)%/#, and red cell distribution width
(RDW).

E. System Descriptions:

1. Device Description:
The ABX MICROS ES 60 is a quantitative, automated hematology analyzer and
leukocyte differential counter for in vitro diagnostic use in clinical laboratories. The
instrument system is comprised of the analyzer and a suite of analytical reagents that
allow for simultaneous quantitative determination of hemoglobin measurement, cell
counting, quality control, calibration, and cleaning. The system is a microprocessor
controlled hematology analyzer used for the in vitro diagnostic testing of whole blood
specimens. It operates in complete blood count (CBC) and Differential (DIFF) mode
using a combination of focused flow impedance and light transmission technologies. It is
available in Closed (CT) or Open Tube (OT) sampling versions.

2. Principles of Operation:
The ABX Micros ES 60 principle of automated cell counting and sizing is used in the
analysis of the whole blood. Each cell suspended in a conductive liquid (diluent) acts as
an insulator. As each cell goes through the aperture, it momentarily increases the
resistance of the electrical path between two submerged electrodes on either side of the
aperture. This causes a measurable electronic pulse. While the number of pulses
indicates particle count, the amplitude of the electrical pulse is proportional to the cell
volume. These pulses are sent to the Signal Conditioner for analog to digital conversion.
Pulse counts and digitized pulse measurements are sent to the System Manager for
processing by the algorithms where the reported parameter values, flags and histograms
are generated.

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 The lysing reagent breaks down the RBC cell membrane and releases the hemoglobin
contained by the cell. The hemoglobin, released by the lysing reagent, combines with the
potassium cyanide from the lysing reagent to form a chromogenous cyanmethemoglobin
compound. This compound is then measured through the optical part of the WBC/HGB
chamber by spectrophotometry at a wavelength of 550 nm.

3. Modes of Operation:

Does the applicant’s device contain the ability to transmit data to a computer, webserver,
or mobile device?

Yes ___X____ or No ________

Does the applicant’s device transmit data to a computer, webserver, or mobile device
using wireless transmission?

Yes ________ or No ___X____

4. Specimen Identification:

Specimen identification is by manual sample identification or with the use of a hand held
barcode scanner.

5. Specimen Sampling and Handling:

Two models of ABX Micros ES 60 are available.

· The Closed Tube (CT) instrument: Cap-piercing mechanism; the blood collection
tube is placed directly in the analyzer without removing the cap.
· The Open Tube (OT) instrument: The cap from the blood collection tube must be
removed before analyzing the sample.

6. Calibration:

ABX Minocal calibrator (k955925) is used for the ABX Micros ES 60 calibration
procedure. Assigned assay values are traceable to reference methods. Calibration is
performed by a HORIBA ABX SAS representative during specific situations such as
installation, maintenance or service intervention.

7. Quality Control:

ABX Minotrol 16 Control (high, normal and low) (k850755) is used to monitor system
performance for all directly measured and calculated CBC and Diff parameters. Assigned
assay values are determined on validated instruments using the appropriate reagents.

8. Software:

2
 FDA has reviewed applicant’s Hazard Analysis and Software Development processes for
this line of product types:

Yes ___X____ or No________

F. Regulatory Information:

1. Regulation section:

CFR 864.5220, Automated differential cell counter

2. Classification:

Class II

3 Product code:

GKZ, Counter, Differential Cell

4. Panel:

Hematology (81)

G. Intended Use:

1. Indication(s) for Use:

The ABX MICROS ES 60 (OT and CT models) is a quantitative multi-parameter,
automated hematology analyzer for in vitro diagnostic use in clinical laboratories to
identify and enumerate the following parameters: WBC, RBC, HGB, HCT, MCV, MCH,
MCHC, RDW, PLT, MPV, LYM%, LYM#, MON%, MON#, GRA%, GRA#, in
K2EDTA and K3EDTA anticoagulated venous whole blood samples of adult patient
population.
It is not intended to be used for pediatric subjects.

2. Special Conditions for Use Statement(s):

For prescription use only

H. Substantial Equivalence Information:

1. Predicate Device Name(s) and 510(k) numbers:

Horiba ABX Micros 60, k030799

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2. Comparison with Predicate Device:

Similarities
Item Device Predicate
(ABX MICROS ES 60) (ABX MICROS 60 - k030799)
Intended Use The ABX MICROS ES 60 (OT and CT The ABX MICROS 60 Hematology
models) is a quantitative multi-parameter, Analyzer is a fully automated
automated hematology analyzer for in vitro (microprocessor controlled)
diagnostic use in clinical laboratories to hematology analyzer used for the in
identify and enumerate the following vitro diagnostic testing of whole
parameters: WBC, RBC, HGB, HCT, blood specimens or blood cell
MCV, MCH, MCHC, RDW, PLT, MPV, concentrates. It operates in complete
LYM%, LYM#, MON%, MON#, GRA%, blood count (CBC) mode.
GRA#, in K2EDTA and K3EDTA
anticoagulated venous whole blood
samples of adult patient population. It is
not intended to be used for pediatric
subjects.
Principles of Measurement
RBC, PLT, HCT, MPV Impedance Same
HGB Spectrophotometry Same
WBC, WBC Differential Impedance Same
(LYM, MON, GRA))
RDW, MCV, MCH, Calculation Same
MCHC
Reagents
Diluent ABX Minidil LMG Same
Lyse ABX Minilyse LMG or ABX Alphalyse Same
360
Cleaner ABX Miniclean Same
Reagent Pack ABX Minipack LMG Same
Concentrated cleaning ABX Minoclair Same
reagent
Quality Controls ABX Minotrol 16 (3 levels) Same
Calibrator ABX Minocal Same
System configuration Bench top Same
Handheld barcode reader (optional)
Integrated barcode reader (CT version
only)
Printer
Sampling mechanism Single tube presentation – open and closed Same
vial sampling
Aspiration pathway Single sampling probe and common Same
aspiration pathway used for all sample
presentation modes
Minimum sample 50 µL Same
volume
Specimen sample 10 µL
volume
Counting aperture
diameters Same
RBC/PLT 50 µm
WBC 80 µm

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 Similarities
Item Device Predicate
(ABX MICROS ES 60) (ABX MICROS 60 - k030799)
Dilution ratios:
RBC/PLT chamber 1/15000 Same

Differences
Item Device Predicate
(ABX MICROS ES 60) (ABX MICROS 60 - k030799)
User Interface Display Automated instrument with 8” LCD touch Automated instrument with 3” LCD
screen display display
Software application Linux-based software application Internally developed software
application
Analytical cycle 1. Draining sequence done by vacuum 1. Draining sequence movement
2. No air bubble. 2. Presence of air bubble at the
end of all cycles
Sample types Whole blood samples only Whole blood samples and blood cell
concentrates
Dilution ratio: WBC 1/260 1/250
chamber
Throughput OT/CT models: 60/50 samples per hour OT/CT model: approx. 60/55
samples per hour

I. Special Control/Guidance Document Referenced (if applicable):

CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods

– 2004
CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedure: A
Statistical Approach – 2003
CLSI EP07-A2: Interference Testing in Clinical Chemistry – 2005
CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient
Samples – 2013
CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement
Procedures – 2012
CLSI EP28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical
Laboratory – 2008
CLSI H20-A2: Reference Leukocyte (WBC) Differential Count (Proportional) and
Evaluation of Instrumental Methods – 2007
CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology
Analyzers – 2010

J. Performance Characteristics:

5
1. Analytical Performance:

a. Method Comparison

1. Comparability between ABX Micros ES 60 CT Vs. ABX Micros ES 60 OT

A total of 237 whole blood specimens from adult patients were analyzed at one
test site in France. Each sample was analyzed in duplicate on the ABX Micros ES
60 CT (Close Tube model) and on the ABX Micros ES 60 OT (Open Tube
model). Bias was estimated at three points for each parameter: the low end of the
distribution of observations, the mid-point, and the high end of the distribution.
Bias was estimated separately for each replicate. Acceptance criteria were met
for all measurands at all levels. These findings support the claim that both Open
Tube and Close Tube models of ABX Micros ES60 device yield comparable
performances across the analytical range for all parameters. Passing Bablok
regression analyses demonstrate comparable performance between Micros ES 60
OT and Micros ES 60 CT models across the analytical range for all the
parameters. Bias data for the first replicate of samples tested in the comparison
study are provided below.

First replicate:
Passing Bablock
%Bias confidence interval 95%
Regression Bias
Claim
r² Slope Intercept Level 1 Level 2 Level 3

WBC 0.998 1.00 0.08 9.80% [-3.4% ; 6.5%] [0.1% ; 1.7%] [0% ; 1.6%]
RBC 0.996 1.00 -0.02 3.40% [-2.8% ; 2.7%] [-1.1% ; 0.8%] [-1% ; 0.6%]
HGB 0.997 0.99 0.32 3.10% [-1.4% ; 7%] [-0.7% ; 2.3%] [-1.1% ; 1.5%]
HCT 0.996 0.98 0.59 1.70% [-1.5% ; 1.7%] [-1.4% ; 0.6%] [-1.8% ; 0.2%]
MCV 0.975 1.00 0 1.20% [-5.2% ; 0%] [-3.3% ; 0%] [-2.7% ; 0.6%]
MCH 0.948 1.07 -1.69 [-4.6% ; 5.6%] [-1.9% ; 5.4%] [-1% ; 6.4%]
MCH 0.706 1.33 -10.57 [-24.8% ; 9.8%] [-11.8% ; 13%] [-8.3% ; 17.2%]
C
RDW 0.896 1.00 0.20 4.00% [-8.6% ; 7.9%] [-6.1% ; 6.1%] [-4.6% ; 5.3%]
PLT 0.987 0.98 5.63 14.7% [-12.8% ; 28.3%] [-3.2% ; 3.7%] [-3.6% ; 0.8%]
MPV 0.955 1.00 -0.20 2.30% [-3.3% ; 3.0%] [-2.4% ; 1.00%] [-2.7% ; 0.7%]
LYM 0.987 1.00 0.30 12.0% [-15.5% ; 43.7%] [-0.2% ; 2.1%] [-0.6% ; 1.7%]
%
LYM 0.999 1.00 0.10 12.0% [0.6% ; 10%] [0.9% ; 4.6%] [0.7% ; 3.9%]
#
MON 0.960 1.03 0.10 26.0% [-6.7% ; 16%] [0.4% ; 6.8%] [0.2% ; 6.6%]
%
MON 0.979 1.00 0.00 13.2% [0% ; 0%] [0% ; 0%] [0% ; 0%]
#
GRA 0.989 1.00 -0.73 9.10% [-10.9% ; 3.0%] [-3.4% ; 0.8%] [-2.0% ; 0.7%]
%
GRA 0.999 1.00 0.00 9.10% [0% ; 0%] [0% ; 0%] [0% ; 0%]
#

2. ABX Micros ES (CT) and ABX Micros ES (OT) vs. Manual Microscopy
100 normal and 100 pathological samples preserved in K2EDTA covering the full
analytic range of the ABX Micros ES60 were analyzed in duplicate on the ABX
Micros ES 60 OT and ABX Micros ES 60 CT. Two slides for each sample were
prepared using May Grunwald Giemsa staining. Samples were classified into
Normal or Abnormal samples for the ABX Micros ES 60 OT, ABX Micros ES 60

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 CT, and the reference method (manual slide microscopy for differential count).
Method comparison studies were designed using the CLSI H20-A2 procedure
by the construction of the "envelope" (or Confidence Interval CI) that takes into
account the imprecision of both the test and the manual method (95% and 99%
confidence interval, respectively).
Based on a Gaussian distribution, 5% of the individual results may fall outside
the 95% envelope. No result should exceed the 99% limits without biological
explanation and a flag. Samples exceeding the 99% limits with a biological
explanation and a flag are considered as outliers.

Evaluation of clinical sensitivity/specificity was based on comparison results

between the slide microscopy and the ABX Micros ES 60 analyzer using 200
samples as follows:

a. ABX Micros ES 60 OT ABX Micros ES 60 CT

Number / Number / Number / Number /
Parameter Percentage of Percentage of Percentage of Percentage of
samples outside samples outside the samples outside the samples outside
the 95% CI 99% CI 95% CI the 99% CI
LYM% 3#/ 1.5% 0# 0% 7# / 3.5% 0# 0%
MON% 5#/ 2.5% 0# 0% 5# / 2.5% 0# 0%
GRA% 2#/ 1% 0# 0% 9# / 4.5% 0# 0%

Samples with a quantitative or a morphological abnormality observed on the reference

method (slide count) or on the predicate Micros 60 were compared with the quantitative
flag on the Micros ES60 OT and CT.

Micros ES 60 OT Micros ES 60 CT Micros 60

Positive Negative Positive Negative Positive Negative

(Abnormal) (Normal) (Abnormal) (Normal) (Abnormal) (Normal)

Positive 97 3 9 4 99 1
Reference (Abnormal)
Method 6
Negative 43 57 5 49 66 34
(Normal) 1

Micros ES 60 OT Micros ES 60 CT Micros 60

% Efficiency 77.0% 72.5% 66.5
% Sensitivity 97.0% 96.0% %
99.0
95% CI Sensitivity 91.5% to 99.0% 90.2% to 98.4% % to 99.8%
94.6
% Specificity 57.0% 49.0% 34.0
95% CI Specificity 47.2% to 66.3% 39.4 to 58.7 % % to 43.7%
25.5
% 69.3% 65.3% 60.0
P
% 95.0% 92.5% %
97.1
P Predictive Value
N
PPV = Positive %
V
NPV = Negative
P Predictive Value
V
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 3. Comparability between ABX Micros ES 60 and ABX Micros 60

A total of 179 whole blood specimens from adult patients were analyzed at four
test sites in the US. Each of the samples was analyzed in duplicate on the ABX
Micros ES 60 (CT model) and on the predicate ABX Micros 60. Bias was
estimated at three points for each parameter: the low end of the distribution of
observations, the mid-point, and the high end of the distribution. Bias was
estimated separately for each replicate. Acceptance criteria were met for all
measurands at all levels. These findings support the claim that the ABX Micros
ES60 candidate device and the ABX Micros 60 predicate device are substantially
equivalent, and demonstrate acceptable levels of bias.

Method Comparison (ABX Micros 60 vs. ABX Micros ES 60 CT), Estimated bias for combined sites.

Lower Higher Lower Higher

Parameter N R2 Slope Limit Limit Intercept Limit Limit
WBC
174 0.999 1.00 0.99 1.00 0.00 0.00 0.07
(103/mm3)
RBC
174 0.989 0.97 0.96 0.99 0.065 0.009 0.120
(106/mm3)
HGB 179 0.991 0.98 0.97 1.00 0.15 0.00 0.33
(g/dL)
HCT 172 0.988 0.98 0.96 0.99 0.48 -0.02 1.06
(%)
MCV 179 0.982 1.00 1.00 1.00 0.00 0.00 0.00
(µm3)
MCH 179 0.924 1.03 1.00 1.08 -0.77 -2.23 0.30

MCHC 179 0.59 1.11 1.00 1.25 -3.36 -7.93 0.30

RDW 179 0.944 0.91 0.87 0.94 1.65 1.15 2.15

(%)
PLT
171 0.995 0.98 0.97 0.99 -2.97 -7.90 1.79
(103/mm3)
MPV 179 0.808 1.05 1.00 1.10 -0.39 -0.82 0.00
(µm3)
LYM 179 0.917 0.97 0.95 0.99 0.24 -0.18 0.71
(%)
LYM #
179 0.996 0.99 0.95 1.00 0.01 0.00 0.06
(103/mm3)
MON 179 0.778 1.11 1.07 1.15 -0.09 -0.35 0.26
(%)
MON # 179 0.961 1.00 1.00 1.03 0.10 0.07 0.10
(103/mm3)
GRA 179 0.913 1.01 0.99 1.03 -1.35 -2.65 -0.14
(%)
GRA # 179 0.998 1.00 0.99 1.00 0.00 0.00 0.02
(103/mm3)
Correlation coefficient; R2 Criteria >0.95 for WBC, RBC, HGB, HCT, PLT

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To establish that the candidate device (ABX Micros ES 60 CT) is comparable with the
predicate device (ABX Micros 60) following bias and r² acceptance criteria was
established for Rep 1 and Rep 2.

Bias Acceptance Criteria

Parameter +/- % Bias Criteria R² Criteria
WBC 9.8 > 0.95
RBC 3.4 > 0.95
HGB 3.1 >0.95
HCT 1.7 >0.95
MCV 1.2 -
RDW 4.0 -
PLT 14.7 >0.95
MPV 2.3 -
LYM% 12 -
LYM# 12 -
MON% 26 -
MON# 13.2 -
GRA% * 9.1 -
GRA# * 9.1 -
* Specific to Neutrophils

b. Precision/Reproducibility:

Repeatability Study
Repeatability was performed in-house using 12 normal and 10 abnormal
fresh whole blood samples collected into tubes containing K2EDTA
anticoagulant. Each sample was run 10 consecutive times on two models of the
Micros ES 60 (ES 60 OT and ES 60 CT), in a single day and all runs were
completed within 8 hours of sample collection. The standard deviation was
compared with the mean value of each parameter and the CV% was calculated.
Results were within the specifications shown below.

Precision (Repeatability) Acceptance Criteria

WBC RBC HGB HCT PLT LYM% MON% GRA%
%CV <2.5 <2 <1.5 <2 <5 <10 <20 <4

Reproducibility
Reproducibility was assessed on three Micros ES 60 instruments at three sites, one
operator per site. At each site; High, Normal, and Low levels of one single lot of
9
Minotrol control material were run in duplicate, twice each day, for a total of 82 days
among the three sites. Total standard deviation and CV% were calculated for each
measurand and results obtained were within specifications shown below. The Micros
ES 60 met the acceptance criteria.

Reproducibility Study – Combined Sites

All Sites Combined Within-Run Between-Day Between-Run Total

Control Total CV%

Parameter Level N Mean CV% CV% CV% CV% Claim
Low 332 2.05 2.78 1.84 1.76 3.77 7.00
WBC
Normal 340 7.47 1.78 1.24 0.00 2.17 5.00
(x 103/mm3)
High 328 20.14 1.11 1.38 0.56 1.86 4.00
Low 332 2.38 1.30 1.20 0.41 1.82 4.00
RBC
Normal 340 4.67 1.11 1.16 0.36 1.65 3.00
(x 106/mm3)
High 328 5.71 1.01 1.33 0.55 1.76 3.00
Low 332 6.01 1.13 0.96 0.62 1.60 5.00
HGB
Normal 340 13.52 0.91 0.94 0.37 1.36 4.00
(g/dL)
High 328 17.90 0.74 1.09 0.49 1.40 3.00
Low 332 16.62 1.35 2.21 0.55 2.65 5.00
HCT
Normal 340 38.11 1.15 1.62 0.59 2.07 4.50
(%)
High 328 51.21 1.07 1.93 0.58 2.28 4.00
Low 332 69.90 0.49 2.02 0.42 2.12 4.00
MCV
Normal 340 81.70 0.35 1.51 0.35 1.59 3.00
(µm3)
High 328 89.68 0.38 1.72 0.34 1.79 2.50
Low 332 75.64 5.99 5.15 3.29 8.56 15.00
PLT
Normal 340 264.63 2.96 1.29 0.46 3.26 10.00
(103/mm3)
High 328 521.83 2.13 1.72 0.53 2.78 7.00
Low 332 13.42 1.86 2.94 0.74 3.56 5.0
RDW
Normal 340 12.96 1.31 3.18 0.84 3.55 5.0
(%)
High 328 12.30 1.26 2.92 0.91 3.31 5.0
Low 332 25.28 1.00 1.25 0.44 1.66 7.0
MCH
Normal 340 28.97 0.74 1.25 0.32 1.49 4.5
(103/mm3)
High 328 31.35 0.72 1.22 0.27 1.44 4.0
Low 332 36.16 1.04 2.14 0.23 2.39 7.0
MCHC
Normal 340 35.48 0.78 1.91 0.36 2.09 4.5
(%)
High 328 34.97 0.80 2.12 0.00 2.26 4.0
Low 332 60.80 1.73 0.00 1.05 2.02 8.00
LYM
Normal 340 32.34 1.66 1.80 0.19 2.45 8.00
(%)
High 328 15.50 1.70 5.25 1.43 5.70 8.00

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 All Sites Combined Within-Run Between-Day Between-Run Total

Control Total CV%

Parameter Level N Mean CV% CV% CV% CV% Claim
Low 332 11.18 6.30 3.95 0.00 7.43 15.00
MON
Normal 340 7.64 4.11 2.77 1.27 5.11 15.00
(%)
High 328 6.56 4.06 9.28 6.55 12.061 11.00
Low 332 27.99 3.45 1.65 2.48 4.56 12.00
GRA
Normal 340 60.02 0.98 1.05 0.00 1.44 4.00
%
High 328 77.94 0.47 0.90 0.45 1.11 3.00
Low 332 1.20 3.61 2.21 2.00 4.68 8.00
LYM# Normal 340 2.37 2.57 3.02 0.23 3.97 8.00
High 328 3.07 2.27 6.68 0.84 7.29 8.00
Low 332 0.20 10.09 5.97 0.00 11.73 15
MON# Normal 340 0.52 6.85 3.60 2.56 8.15 14
High 328 1.27 4.85 9.45 7.04 12.741 11
Low 332 0.66 8.23 0.74 3.13 8.83 12.0
GRA# Normal 340 4.59 2.15 0.28 0.29 2.19 4.0
High 328 15.79 1.24 0.86 0.63 1.63 3.0
1
: Exceeds acceptance criteria limits; however, these results support the claim of reproducibility for low, normal
and high levels of controls with the overall reproducibility claim being met in 97% of the tests.

c. Linearity:
Linearity was assessed s using R&D Systems CBC-LINE high and low range
linearity kits according to the manufacturer’s instructions. The expected values of the
kit samples were considered the “true values”. Each level was run in replicates of
four (n=4) as recommended by the kit supplier. For each level, the 4 replicate results
were plotted versus the theoretical value. The findings of the polynomial regression
analysis indicate that the ABX Micros ES 60 exhibits linearity across the claimed
range. The Micros ES 60 met the acceptance criteria.

Analytical Measuring Range

Parameter AMR on Micros
ES60
WBC (103/mm3) 0.8 – 100
RBC (106/mm3) 0.7 – 8
PLT (103/mm3) 42 – 2200
HGB (g/dL) 0.6 - 24.0
HCT (%) 8.0 - 70.0

d. Carryover:

The potential for sample carryover was tested in duplicate on the ABX Micros ES 60
OT and CT instruments using alternating high and low sample concentrations.
Carry-over effects were evaluated by assaying a diluted sample 3 times, low (L1-3)

11
 then a sample with high cell concentrations 3 times (H1-3), followed immediately by
testing a diluted sample consecutively 3 times (L4-6). Clinical samples were either
concentrated or diluted to obtain the following target high and low sample values:

High Samples Low Samples

WBC 40 to 80 x103/mm3 0.8 to 1.2 x 103/mm3
RBC 6 to 9 x 106/mm3 1 to 2 x106/mm3
HGB 15 to 20 g/dL 5 to 7 g/dL
PLT 500 to 1000 x103/mm3 15 to 50 x103/mm3

All carry-over results were within specifications, <1% for the ABX Micros ES OT
and CT Systems for the following parameters: WBC, RBC, HGB, and PLT.

e. Interfering Substances:

The study to evaluate interference effect followed two methodologies:

By addition: The evaluation of the effect of potentially interfering substances added

to the sample of interest. A potential interfering substance was added to a sample and
the bias relative to a control portion of the sample was evaluated ("paired-difference
testing"). This bias was compared to the acceptance criteria. For all tests performed
with potential interferents, the bias remained below the acceptable limit. Therefore,
no significant interference was observed for urea, bilirubin, lipemia, and hemolysis.
Interference of WBC counts has been observed in presence of yeast in the sample.

By comparison: Evaluation of the bias of individual specimen. Representative patient

specimens and a control sample (without interferent) were run in duplicate using the
Micors ES 60 versus the reference device, Micros 60, to obtain a comparative
measurement. The bias versus comparative measurement values was plotted for each
specimen group. Both measurement procedures had 10 to 20 samples in each group
to demonstrate sufficient precision. A comparable effect was observed on the ABX
Micros ES 60 and the reference device when interference was tested for the
following: WBC fragments, myelocytes, nucleated RBC, RBC inclusion, RBC
agglutinins / cold agglutinins / RBC rouleaux, dual RBC population, RBC fragments,
target cells, platelet aggregates, platelet satellitism, macrothrombocytes / large
platelets, small RBC leukocytosis.
Interference of megakaryoctes with WBC and parasites with monocyte counts could
not be tested, but that are well described in literature.

2. Other Supportive Instrument Performance Data Not Covered Above:

1. Specimen Stability Studies:

Eleven (11) whole venous blood specimens (collected in K2EDTA and K3EDTA)
were analyzed on the ABX Micros ES 60 (OT model) at one site in France in order to
cover the AMR for the majority of measurands. Following the collection (T0), each
specimen was divided in half, with one sample stored at ambient temperature (20-

12
 24oC) and the other stored under refrigerated conditions (2-8oC). Testing for stability
was performed at 2, 6, 8, 10, 24, 36, 48, 60 and 72 hours after T0. The first aliquot of
each specimen was run sequentially in any order. The second aliquot was run in
reverse order to minimize the effects of carryover and drift. The acceptance criteria
for sample stability is given as an acceptable maximum bias of the value at T with the
value at T0. All data met specifications.

Parameters Sample stability when Sample stability when

stored refrigerated stored at room temperature
(2-8°C) (20-24°C)
WBC, RBC, HGB, HCT, 48 hours 36 hours
MCV, MCH, MCHC, PLT
RDW 36 hours 10 hours
MPV 24 hours 24 hours
LYM%, LYM#, MON%, 24 hours 8 hours
MON#, GRA%, GRA#

2. Comparability between Anticoagulants

A total of 52 normal and pathological blood specimens were analyzed on the ABX
Micros ES 60 (CT model) at three sites in the US. Testing was performed using a
different instrument and operator at each site. The specimens used in this study were
venous blood specimens that were prospectively specifically collected for this study.
Each subject provided blood collected in both K2EDTA and K3EDTA. Each of the
samples was analyzed in duplicate on the ABX Micros ES 60 CT. Bias was
estimated at three points for each parameter: the low end of the distribution of
observations, the mid-point, and the high end of the distribution. Bias was estimated
separately for each replicate. Acceptance criteria were met for all measurands at all
levels. These findings support the claim that K2EDTA and K3EDTA specimens give
comparable results as measured on the ABX Micros ES 60 hematology analyzer.

3. Determination of limit of blank, lower limits of detection and quantitation:

Verification of Limit of Blank (LoB)

Plasma samples, obtained by centrifugation of normal samples, were used as blank
samples, in order to be as close as possible as the blood sample matrix. To estimate
the LoB, a total of 60 repeated measurements of different plasma were run in the
same series (5 different samples run 12 times). This test is performed on 2
instruments uisng two reagents lots. Results on Micros ES 60 OT and Micros ES60
CT were similar and met specifications.
LoB obtained from 60 repeated measurements of 5 different plasma samples:

Measurand LoB
WBC 0.1x103/mm3
RBC 0.01x106/mm3
HCT 0.1 %
PLT 1x103/mm3

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 Verification of Limit of Detection (LoD)
A set of six samples with very low parameter concentration (i.e. in the range of LoB
and 4 x LoB) were run 10 times over several days. LoD was estimated from the
calculation of the pooled standard deviation of 60 results. Testing was performed on
two (2) instruments with two reagents lots. Results on Micros ES 60 OT and Micros
ES 60 CT were similar and met specifications. Testing from 10 runs of 6 low
samples on each instrument resulted in the following results for LoD:

Measurand LoD
WBC 0.2x103/mm3
RBC 0.01x106/mm3
HGB 0.5 g/dL
HCT 0.2 %
PLT 4x103/mm3

Verification of Limit of Quantitaion (LoQ)

To estimate the limit of quantitation, several ranges of linearity in low concentrations
were prepared. Between 3 to 6 samples by concentratin level were prepared and run
at least 5 times each using 40 replicates per level. The LoQ data are considered
acceptable when the %Total-error is smaller than the desired total error for each
measurand. This test is performed on two (2) instruments with two reagents lots.
Results on Micros ES 60 OT and Micros ES 60 CT were similar and passed
acceptance limits. Testing from 40 runs of 4 samples on each instrument resulted in
the following results for LoQ:

Measurand LoQ
WBC 0.8x103/mm3
RBC 0.7x106/mm3
HGB 0.6 g/dL
HCT 8%
PLT 42x103/mm3

4. Reference Intervals:

Verification of Adult Reference Intervals

Adult reference intervals were assessed on a total of 275 (135 male and 140 female)
normal adult samples (whole blood samples collected in K2EDTA). Samples were
analyzed in duplicate on the ABX Micros ES 60 (OT model) and ABX Micros ES 60
(CT model) at one test site in the US. The nonparametric data analysis method was
used, depending only on the ranks of the reference data arranged in order of
increasing size. Per EP28-A3, the reference interval is determined to be between and
including the lower and upper reference limits, which enclose 95% of the values from
the reference population subjects. Confidence intervals for the reference limit were
calculated using a 90% probability (90% CI).

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 Defined reference values are not significantly different between the ABX Micros ES
60 OT and CT models. For each gender, a single reference interval applicable
(Shared Interval) on both versions of the analyzers has been defined as described in
the following table.
MALES FEMALES
MICROS ES60 (N=135) (N=140)
Reference Interval
LOW HIGH LOW HIGH
WBC (103/mm3) 4.3 9.6 4.2 10.3
RBC (106/mm3) 4.1 5.7 4.0 5.1
HGB (g/dl) 12.6 16.7 11.6 15.1
HCT (%) 38.3 50.8 35.8 46.4
MCV (µm3) 83 97 83 98
MCH (pg) 26.7 32.3 26.8 32.5
MCHC (g/dl) 31.7 34 31.8 34.0
RDW (%) 11.1 14.4 11.3 13.9
PLT (103/mm3) 156 370 181 393
MPV (µm3) 6.3 9.1 6.5 9.0
LYM (103/mm3) 1.1 3.1 1.2 3.4
MON (103/mm3) 0.1 0.6 0.1 0.6
GRA (103/mm3) 2.6 7.0 2.7 7.4
LYM (%) 16.5 44.7 17.7 45.2
MON (%) 3.1 8.3 3.3 8.1
GRA (%) 49.1 76.9 49.2 77.7

K. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

L. Conclusion:

The submitted information in this premarket notification is complete and supports a

substantial equivalence decision.

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