1. AEROSET® & ARCHITECT® cSystem™
MULTIGENT® CRP Vario™
REF 6K26-40

2. Agenda Clinical Utility Methodology Sample Handling Reagent Handling
Calibration
Quality Control
Reportable Range
Interference
Precision
Method Comparison
CAP Performance
Troubleshooting tips
Questions and Answers

3. MULTIGENT® CRP Vario™
Three CRP Calibrator sets are available for use with the three different CRP assay methods. The calibrator sets to use with each assay method are summarized in the table:
Control
MULTIGENT CRP Control HS REF 6K26-40 is available for use with the High Sensitivity (CRP16) method.
Ranges for appropriate Bio-Rad controls have been established.
Complaint handling:
Abbott has responsibility for initial complaint registration.
Sentinel (the vendor) will investigate level II complaints.
Calibrator Set
Assay Application
List Number
Configuration
Assay Name
Method
6K26-13 (Std)
7 x 2 mL
CRP32
CRP Standard
6K26-14 (HS)
1 x 2 mL
CRP16
CRP High Sensitivity
6K26-15 (WR)
CRP48
CRP Wide Range

4. Assay Disk MULTIGENT® CRP VARIO™
ARCHITECT® MULTIGENT Assay Disk Version 2.00
8K50-02 Conventional/Alternate Units
8K51-02 SI/Alternate Units
No AEROSET® Assay Disk will available.

5. Clinical Utility of CRP VARIO™
CRP Vario assay is intended for the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma with variable assay ranges covering a wide analytical measurement range.
Three different applications of the assay are available for use:
CRP Standard CRP32 –measures normal to high levels of CRP
CRP HS (High Sensitivity) CRP16 – identifies extremely low levels of CRP
CRP WR (Wide Range) CRP48 – measures within the standard range but with an extended linearity allowing for higher measurement and reduced dilutions

6. Clinical Utility of CRP VARIO™
CRP testing is used for:
Prognosis and extent of coronary atherosclerosis - elevated levels are linked to the occurrence
Progression of both stable and unstable angina.
Monitoring disease activity & response.
Examples:
Monitor CRP following surgery
Managing neonatal septicemia (in many areas, all neonate patients are tested for CRP level)
Source: Jacobs and Demott, Editors, Laboratory Test Handbook 5th Edition, 2001, Lexi-comp, Inc, Hudson, OH

7. Clinical Utility of CRP VARIO
Increased CRP values are associated with:
Injury/Trauma
Infection
Stress
Myocardial Infarction
Surgery
Inflammation
Tumor growth
Decreased CRP values are associated with:
Normal (absence of disease state)
*NOTE: MULTIGENT CRP Vario does not have the right to claim cardiac risk screening as a function of clinical utility and/or intended use.
High sensitivity CRP is not specific for cardiovascular disease.

8. MULTIGENT® CRP VARIO™ Methodology
Methodology: Turbidimetric/Immunoturbidimetric
Chemical Reaction:
CRP + Anti-CRP Antibody/latex Agglutination due to CRP:Antibody complex
CRP is a latex immunoassay developed to measure blood CRP levels in serum and plasma.
An antigen-antibody reaction occurs between CRP in sample and anti-CRP antibody, which has been adsorbed to latex particles, resulting in agglutination.
This agglutination is detected in an absorbance change (572 nm), with the rate of change being proportional to the quantity of CRP in the sample.

9. MULTIGENT® CRP VARIO™ Sample Handling
Specimen Requirements:
Serum
Plastic tubes
With or without gel barrier
Plasma
Lithium or Sodium Heparin or EDTA

10. MULTIGENT® CRP VARIO™ Sample Handling
Sample Tubes tested and found acceptable:
Vendor
Ref
Tube
BD Europe
369032
Serum tube
367957
Serum with Gel separator
367869
Na - heparin
368884
Li-heparin (17 IU/mL)
367374
Li -heparin with PST II gel barrier
368856
EDTA-K2

11. MULTIGENT® CRP VARIO™ Sample Handling
Specimen storage:
Stored specimens must be inspected for particulates. If present, mix and centrifuge the specimen to remove particulates prior to testing.
Sample volume:
Maximum storage
Temperature
Serum/Plasma
20 to 25°C
15 days
2 to 8°C
2 months
-20°C
3 years
Method
Sample volume
Dilution*
High Sensitivity
4 μl
1:10
Standard & Wide Range
2 μl
1:5
*The system performs the dilution and automatically corrects the concentration by multiplying the result by the appropriate dilution factor.

12. MULTIGENT® CRP VARIO™ Reagent Handling
MULTIGENT CRP Vario supplied as a two-reagent kit:
REF 6K26-40
Kit Configuration R1
3 x 90 mL R2
Tests per kit:
High Sensitivity = 2,192
Standard = 2,192
Wide Range = 1,843
Reagent is liquid, ready-to-use, two reagent kit.
Storage: 2 to 8°C.
Unopened kit is stable to the expiration date.
Remove any air bubbles with an applicator stick.
Reagent onboard stability is 60 days.

13. MULTIGENT® CRP VARIO™ Calibration
CRP Vario calibrators are liquid ready-to-use.
Unopened calibrators are stable until expiration date when stored at 2 to 8°C.
Opened calibrators are stable for 3 months at 2 to 8°C if contamination is avoided and vials are recapped immediately after use.
Calibration curve is stable for 15 days.
Traceability of the method is verified using CMR 470 (Certified Reference Material) from BCR (EC Community Bureau of Reference), corresponding to RPPHS (Reference Preparation for Protein in Human Serum).

14. MULTIGENT ® CRP VARIO™ Calibration Curve - ARCHITECT® CRP High Sensitivity (CRP16)

15. MULTIGENT ® CRP VARIO™ Calibration Curve - ARCHITECT® CRP Standard (CRP32)

16. MULTIGENT ® CRP VARIO™ Calibration Curve - ARCHITECT® CRP Wide Range (CRP48)

17. MULTIGENT ® CRP VARIO™ Curve -AEROSET® CRP High Sensitivity (CRP16)

18. MULTIGENT ® CRP VARIO™ Curve -AEROSET® CRP Standard (CRP32)

19. MULTIGENT ® CRP VARIO™ Curve -AEROSET® CRP Wide Range (CRP48)

20. Quality Control
MULTIGENT CRP Control HS REF 6K26-21 is available for the High Sensitivity application.
BioRad controls are available for both AEROSET® and ARCHITECT® customers
BioRad peer value information can be found on WWCS webpage
BIO-RAD
Control Product Name
Catalog Number
Configuration
Liquichek Immunology* Chemistry Control
L-1: 591
L-2: 592
L-3: 593
6 x 1 mL
Lyphochek Immunology Plus Chemistry Control
Bilevel: 430
12 x 1 mL
*There is an additional size packaged as 6 x 3mLs. The list numbers are 594, 595 and 596.

21. MULTIGENT ® CRP VARIO™ Reportable Range
Serum and Plasma
Reportable Range:
* To convert results from mg/dL to mg/L multiply mg/dL by 10.
NOTE: All three methods were tested for prozone effect up to a concentration of 100 mg/dL (1,000 mg/L). No effect was observed within the linear range of the assay.
Limit of Quantitation (LOQ):
LOQ is the analyte concentration at which the CV = 20%.
High Sensitivity method
0.01 to mg/dL (0.1 to 160 mg/L)*
Standard method
0.02 to mg/dL (0.2 to 320 mg/L)
Wide Range
0.02 to mg/dL (0.2 to 480 mg/L)
High Sensitivity Method
0.01 mg/dL (0.1 mg/L)
Standard and Wide Range Method
0.02 mg/dL (0.2 mg/L)

22. MULTIGENT CRP VARIO™ Interference
Interfering substances:
MULTIGENT CRP Vario assay is not affected by the presence of the following interferents up to the concentrations indicated below:
Interferring Substance
Interferent Concentration
Bilirubin, conjugated and fetal
30 mg/dL (513 μmol/L)
Hemoglobin
500 mg/dL (5.0 g/L)
Intralipid
1,500 mg/dL (15 g/L)
Rheumatoid factor
550 IU/mL (650 kU/L)

23. MULTIGENT® CRP VARIO™ Precision
Representative data from a 5 day study with two runs and four
replicates of each control per day are summarized below.
CRP High Sensitivity Method:
Control
Level 1
Level 2
Level 3
Level 4 N
Mean (mg/L) 40
0.6
5.0
14.9
53.0
Within Run SD
%CV
0.022
3.62
0.07
1.32
0.13
0.86
0.26
0.50
Between Run SD
0.005
0.85
0.02
0.38
0.10
0.64
0.33
0.62
Total SD
3.72
1.46
0.16
1.04
0.40
0.76

24. MULTIGENT® CRP VARIO™ Precision
Representative data from a 5 day study with two runs and four replicates of each control per day are summarized below.
CRP Standard Method:
CRP Wide Range Method:
Control
Level 1
Level 2
Level 3 N
Mean (mg/L) 40
5.0
14.9
53.8
Within Run SD
%CV
0.06
1.11
0.14
0.93
0.50
0.92
Between Run SD
0.04
0.80
0.13
0.89
0.47
0.87
Total SD
0.07
1.41
0.18
1.21
0.64
1.19
Control
Level 1
Level 2
Level 3 N
Mean (mg/L) 40
5.4
18.3
263.8
Within Run SD
%CV
0.07
1.29
0.17
0.93
2.99
1.13
Between Run SD
0.05
0.92
0.13
0.71
2.65
1.00
Total SD
0.08
1.48
0.22
1.18
4.02
1.52

25. MULTIGENT® CRP VARIO™ Method Comparison
Serum results from the MULTIGENT CRP Vario methods on the AEROSET system were compared with the results from a commercially available nephelometric methodology.
Serum results from the MULTIGENT CRP Vario methods on an ARCHITECT cSystem were compared with the results on the AEROSET System.
CRP High Sensitivity Method
AEROSET vs.
Nephelometer
ARCHITECT vs. AEROSET N 45
Y – Intercept (95% CI*)
-0.24 to 0.54
-0.33 to 0.45
Correlation Coefficient
0.9994
Slope (95% CI*)
0.985 to 1.006
0.975 to 0.996
Standard Error of Estimate
0.96
Range (mg/dL)
1.0 to 104.0
1.1 to 103.3
CRP Standard Method
AEROSET vs.
Nephelometer
ARCHITECT vs. AEROSET N 54
Y – Intercept (95% CI*)
-0.68 to 0.50
-0.64 to 0.46
Correlation Coefficient
0.9996
0.9997
Slope (95% CI*)
1.004 to 1.020
0.977 to 0.991
Standard Error of Estimate
1.64
1.58
Range (mg/dL)
1.0 to 219.0
0.6 to 223
* CI = Confidence Interval

26. MULTIGENT® CRP VARIO™ Method Comparison
Serum results from the MULTIGENT CRP Vario methods on the AEROSET system were compared with the results from a commercially available nephelometric methodology.
Serum results from the MULTIGENT CRP Vario methods on an ARCHITECT cSystem were compared with the results on the AEROSET System.
CRP Wide Range Method
AEROSET vs.
Nephelometer
ARCHITECT vs. AEROSET N 59
Y – Intercept (95% CI*)
-1.26 to 1.53
-1.44 to 2.04
Correlation Coefficient
0.9989
0.9982
Slope (95% CI*)
1.023 to 1.051
0.968 to 0.999
Standard Error of Estimate
4.10
5.28
Range (mg/dL)
1.0 to 286.0
0.7 to 301.2
* CI = Confidence Interval

27. MULTIGENT® CRP VARIO™ Method Comparison
For the MULTIGENT CRP High Sensitivity method only, serum results
from an ARCHITECT cSystem and the AEROSET System were also
compared with the results from a commercially available turbidimetric
methodology.
CRP High Sensitivity Method
AEROSET vs.
Turbidimetric Method
ARCHITECT vs. N 55
Y – Intercept (95% CI*)
-0.01 to 0.07
-0.02 to 0.10
Correlation Coefficient
0.9995
0.9990
Slope (95% CI*)
0.992 to 1.009
1.001 to 1.035
Standard Error of Estimate
0.10
0.14
Range (mg/dL)
0.2 to 13.6
* CI = Confidence Interval

28. MULTIGENT ® CRP VARIO™ CAP Performance
CAP Proficiency Testing (PT) for MULTIGENT CRP assay was performed in-house on the Architect c8000 analyzer using CAP PT materials :CRP-01 and CRP-02.
S-A 2008 CAP Survey Results (Information Only) MULTIGENT Abbott Turbidimetric Method Mean*
CRP
CRP
NOTE: results units = mg/L
*Labs reporting = 53

29. Troubleshooting Tips
Reagent performance does not meet claim: Estimated Number of Tests not obtained
Probable Cause(s) Corrective Action(s)
Operator error. Ensure the estimated number of tests is
based on the minimum reagent fill volume per kit (in total), not per set enclosed in the kit. In addition, estimated test number is
based on necessary calibrations and QC, plus patient runs.

30. Questions and Answers Question:
Why do we have MULTIGENT CRP Vario when we have an Abbott CRP already available?
Answer:
MULTIGENT CRP Vario offers two additional applications that are not currently available with the Abbott CRP: High Sensitivity and Wide Range which cover low sensitivity and extended linearity.

31. Questions and Answers Question:
Do we have the cardiac risk assessment claim for the high sensitivity application CRP HS?
Answer:
No, however, we do offer the application for high
sensitivity and we are extremely competitive with other
CRP applications currently available. CRP HS, according
to the FDA website, can be used for evaluation of
conditions thought to be associated with inflammation,
in otherwise healthy individuals.

32. Questions and Answers Question:
Why is MULTIGENT CRP Vario kit size so large and will my customer have a lot of waste?
Answer:
CRP Vario cartridges have 60 days for on-board stability and 15 days calibration stability. If your customer runs >7 patient samples per day plus calibrations and quality control, they will not waste reagent.
End of Document