1. ARCHITECT cSystems only
Multigent C-Reactive Protein (CRP) Harmonization
6K26-30, 6K26-41
Worldwide Launch: September 2010
REF
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures.
c8000 Project Notebook, , version 5
© 2010 Abbott

2. Assay Disk Information Clinical Utility Reaction & Methodology
Agenda
Launch Strategy
Assay Disk Information
Clinical Utility
Reaction & Methodology
Sample Handling
Reagent Handling
Calibration
Quality Control
Performance Data
Interference
Precision
Method Comparison
Product Summary
Q&A
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

3. Multigent CRP Launch Strategy
The Multigent assays are available for use on the ARCHITECT cSystems.
Complaint handling:
Abbott has responsibility for initial complaint registration.
Sentinel (the vendor) will investigate Level II complaints.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

4. Multigent CRP Launch Strategy Key updates to CRP assays
MULTIGENT CRP Vario (6K26) Enhancements…
convert from Sentinel orange cartridges to Abbott reagent cartridges
convert from Sentinel cartons / boxes to Abbott cartons
convert to a global Abbott branded labeling
have a size code change to reflect the change
New smaller kit size
Discontinue duplicate products….
Abbott CRP (8G65-21)
Abbott CRP Calibrator (8G68-02)
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

5. Multigent CRP Launch Strategy Activities and Timeline
September 2010
Customer Launch Letter – Release in
September for distribution to customers.
Customers convert to the enhanced
CRP Vario Reagents, Cals & QC
within 7 months of availability.
Current sizecodes will be discontinued.
CRP Vario Reagent
CRP Cal Set
CRP Cal WR
CRP Cal HS
CRP Control HS
Discontinue Abbott CRP (8G65)
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

6. Assay Disk Information
Multigent CRP parameters Standard CRP, Assay 2973, High Sensitivity CRP Assay 2974, and Wide Range CRP, Assay 2975 are available on the following recently released ARCHITECT cSystems assay disks.
Assay Disks
List Number
ARCHITECT c Systems MULTIGENT Assay Disk
Conventional Units / Alternate Units
8K50-04
SI Units / Alternate Units
8K51-04
ARCHITECT c Systems Special Chemistry Assay
Disk Conventional Units / Alternate Units
2P10-03
Disk SI Units / Alternate Units
2P11-03
Assay configuration is provided in the assay specific application sheets.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

7. Clinical Utility
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.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

8. Clinical Utility CRP testing is used as:
A marker or general diagnostic indicator of infections and inflammation.¹
One of the fastest reacting acute phase protein²
Levels may rise more than 1000-fold during an acute phase response²
Prognosis and extent of coronary atherosclerosis - elevated levels are
linked to the occurrence.³
Progression of both stable and unstable angina.³
Monitoring disease activity & response.³
Example: Monitor CRP following surgery
Source: 1. Multigent CRP Vario 6K26 Package Insert.
2. FBR Guide
3. Jacobs and Demott, Editors, Laboratory Test Handbook 5th Edition, 2001, Lexi-comp, Inc, Hudson, OH
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

9. Clinical Utility 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.
Source: Jacobs and Demott, Editors, Laboratory Test Handbook 5th Edition, 2001, Lexi-comp, Inc,
Hudson, OH, FBR Guide
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

10. Multigent CRP Reaction & Methodology
Step 1: Sample containing CRP is added to Reagent 1 (Glycine Buffer).
Step 2: Reagent 2 containing Antibody (anti-human CRP rabbit serum) is added to the sample/Reagent 1 mix.
Sample/ Reagent 1
Reagent 2 Y Y Y Y Y Y Y + ↑
CRP ↑
CRP Specific Antibody
Step 3: When sample containing CRP is added to R1 and mixed with the antibody in Reagent 2 insoluble aggregates form. The degree of agglutination is directly proportional to the concentration of CRP in the sample. This is determined by measuring the decrease of transmitted light caused by the aggregates at a wavelength of 572 nm. Y Y Y Y Y Y Y Y Y
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

11. Multigent CRP methodology
Turbidimetric/Immunoturbidimetric
Available in the CAP Diagnostic Immunology Survey
Contact CAP for the current coding.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

12. Multigent CRP Sample Handling
Specimen Requirements:
Serum
Plastic tubes
With or without gel barrier
Plasma
Lithium Heparin (With or without gel barrier) or Sodium Heparin or EDTA
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

13. Multigent CRP Sample Handling
Specimen storage:
* Guder WG, da Fonseca-Wollheim F, Heil W, et al. The Quality of Diagnostic Samples. Darmstadt,
Germany: GIT Verlag; 2001:24-5.
Repeated freeze/thaw cycles should be avoided to minimize
potential protein degradation.
Stored specimens must be inspected for particulates. If present, mix and centrifuge to remove particulates prior to testing.
Temperature
Maximum Storage *
Serum/Plasma
20 to 25°C
2 to 8°C
-20°C
15 days
2 months
3 years
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

14. Multigent CRP Reagent Handling
2 Reagent Kit Configurations
Tests/kit
Estimated calculation is based on the minimum reagent fill volume per kit.
Reagent is liquid, ready-to-use, 2 reagent kit
Storage 2 to 8°C.
Unopened kit stable to expiration date
Remove any air bubbles, if present, with an applicator stick
Reagent onboard stability – 60 days (1440 hours)
6K26-30 R1
2 x 37 mL R2
6K26-41
3 x 86 mL
3 x 88 mL
Method
6K26-30
(# of tests)
6K26-41
High Sensitivity
600
2,192
Standard
Wide Range
500
1,836
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

15. Multigent CRP Calibration Standard Method
Calibration interval is 15 days (360 hours)
Use the Multigent CRP Calibrator K26 –10
Calibration: Standard method uses six levels of CRP Calibrator.
REF
Standard Method
Size
CRP 05
1 x 2 mL
CRP 10
CRP 20
CRP 40
CRP 160
CRP 320
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

16. Multigent CRP Calibration Wide Range Method
Calibration interval is 15 days (360 hours)
Use the Multigent CRP Calibrator K26 –10 substituting CRP 320 with
CRP WR K26-12
Calibration: Wide Range method uses six levels of CRP Calibrator.
REF
REF
Wide Range Method
Size
CRP 05
1 x 2 mL
CRP 10
CRP 20
CRP 40
CRP 160
CRP WR (6K26-12)
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

17. Multigent CRP Calibration High Sensitivity Method
Calibration interval is 15 days (360 hours)
Use the Multigent CRP Calibrator K26 –10 substituting CRP 320 with
CRP HS K26-14 and adding CRP 80 from 6K26 –10
Calibration: High Sensitivity method uses six levels of CRP Calibrator.
REF
REF
High Sensitivity Method
Size
CRP HS (6K26-14)
1 x 2 mL
CRP 05
CRP 10
CRP 20
CRP 80
CRP 160
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

18. Multigent CRP Calibration
Do not freeze calibrators.
Calibrators are liquid ready to use.
The calibrators are prepared by diluting CRP with human serum.
Calibrator values are verified using ERM-DA472/IFCC (European Reference
Material/International Federation Clinical Chemistry) from IRMM(Institute for Reference
Materials and Measurements).
The concentration of the calibrators are indicated in each respective Multigent CRP
Calibrator package insert and on the vial labels.
Unopened calibrators are stable until the expiration date indicated on the package when
stored at 2-8 °C.
Opened calibrators are stable for 3 months at 2 to 8°C if contamination is avoided and
vials are recapped immediately after use.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

19. Multigent CRP Calibration Curve – ARCHITECT cSystems CRP High Sensitivity (CRP16)
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

20. Multigent CRP Calibration Curve – ARCHITECT cSystems CRP Standard (CRP32)
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

21. Multigent CRP Calibration Curve – ARCHITECT cSystems CRP Wide Range (CRP48)
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

22. Multigent CRP Quality Control
The High Sensitivity method uses the Multigent CRP Control HS, K26-21
Multigent CRP Control HS, List No. 6K26-21 contains:
Other acceptable controls are :
Immuno Control K32-20 (Not available in the US)
Immuno Control K32-21 (Not available in the US)
These are the only controls approved for use with this assay.
REF
Control Product Name
Configuration
CRP Control HS
3 x 2 mL
REF
REF
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

23. Multigent CRP Performance Data
Serum and Plasma
Normal Expected Range (adults): < 0.5 mg/dL (< 5 mg/L)
Reportable Range:
High sensitivity method to mg/dL (0.1 to 160 mg/L)
Standard method to mg/dL (0.2 to 320 mg/L)
Wide Range method to mg/dL (0.2 to 480 mg/L)
Limit of Quantitation (LOQ) =
High sensitivity method mg/dL (0.1 mg/L)
Standard and Wide Range methods mg/dL (0.2 mg/L)
LOQ represents the lowest measurable concentration at which the CV
< 20% and the recovery is within +/- 20% of expected value.
Note: SI units are mg/L. To convert results from mg/dL to mg/L,
multiply by 10.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

24. Multigent CRP Interference
Interference studies were conducted using an acceptance criteria of +/- 5% deviation from the target value. No interference was observed at the concentrations below.
Interfering 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)
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

25. Multigent CRP Precision
Representative data from precision study are summarized
below. The precision acceptance criteria for the CRP assay is
≤6% Total CV.
CRP High Sensitivity Method:
Representative Data
LEVEL N
Concentration Mean
(mg/L)
CV (%)
Within Run
Total
Control Level 1 40
0.462
4.0
4.66
Control Level 2
4.92
0.72
0.87
Control Level 3
11.35
1.30
1.62
Control Level 4
45.88
0.65
0.85
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

26. Multigent CRP Precision
The precision acceptance criteria for the CRP assay is
≤6% Total CV.
CRP Standard Method:
Representative Data
LEVEL N
Concentration Mean
(mg/L)
CV (%)
Within Run
Total
Control Level 1 40
5.10
1.97
2.15
Control Level 2
18.30
0.59
1.04
Control Level 3
73.30
0.50
0.54
Control Level 4
319.40
0.65
0.85
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

27. Multigent CRP Precision
The precision acceptance criteria for the CRP assay is
≤6% Total CV.
CRP Wide Range Method:
Representative Data
LEVEL N
Concentration Mean
(mg/L)
CV (%)
Within Run
Total
Control Level 1 40
5.20
1.16
1.91
Control Level 2
18.40
0.99
1.17
Control Level 3
90.20
0.77
1.39
Control Level 4
268.0
1.24
1.83
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

28. Method Comparison CRP Vario (6K26) vs. Abbott CRP (8G65)
Method Comparison testing was performed on ARCHITECT c16000
Least Squares
Passing-Bablok
Bias / Total Error N
Corr Coef
Slope
Intercept
%95 CI
95% CI
Mean Bias
Mean % Bias
119
0.9996
1.01
(1.00, 1.01)
-0.06
(-0.09, -0.03)
0.98
(0.97, 0.99)
-0.00
(-0.01, 0.01)
-0.03
-1.8
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

29. Multigent CRP Method Comparison
Serum results from the Multigent CRP High Sensitivity assay on an
ARCHITECT cSystem were compared with the results on the
AEROSET system.
Serum results from the Multigent CRP assay on an AEROSET
system were compared with results on the Beckman Image.
CRP High Sensitivity Method
ARCHITECT cSystem vs.
AEROSET
(1.1 to mg/L)
AEROSET vs.
Comparative Method
(1.0 to mg/L) N 45
Y – Intercept
-0.33 to 0.45
-0.24 to 0.54
Correlation Coefficient
0.9994
Slope
0.975 to 0.996
0.985 to 1.006
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

30. Multigent CRP 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
ARCHITECT vs.
Turbidimetric
(0.2 to 13.6 mg/L)
AEROSET vs. N 55
Y – Intercept
-0.02 to 0.10
-0.01 to 0.07
Correlation Coefficient
0.9990
0.9995
Slope
1.001 to 1.035
0.992 to 1.009
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

31. Multigent CRP Method Comparison
Serum results from the Multigent CRP Standard assay on an
ARCHITECT cSystem were compared with the results on the
AEROSET system.
Serum results from the Multigent CRP assay on an AEROSET system
were compared with results on the Beckman Image.
CRP Standard Method
ARCHITECT cSystem vs.
AEROSET
(0.6 to 223 mg/L)
AEROSET vs.
Comparative Method
(1.0 to mg/L) N 54
Y – Intercept
-0.64 to 0.46
-0.68 to 0.50
Correlation Coefficient
0.9997
0.9996
Slope
0.977 to 0.991
1.004 to 1.020
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

32. Multigent CRP Method Comparison
Serum results from the Multigent CRP Wide Range assay on an
ARCHITECT cSystem were compared with the results on the
AEROSET system.
Serum results from the Multigent CRP assay on an AEROSET system
were compared with results on the Beckman Image.
CRP Wide Range Method
ARCHITECT cSystem vs.
AEROSET
(0.7 to mg/L)
AEROSET vs.
Comparative Method
(1.0 to mg/L) N 59
Y – Intercept
-1.44 to 2.04
-1.26 to 1.53
Correlation Coefficient
0.9982
0.9989
Slope
0.968 to 0.999
1.023 to 1.051
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

33. Multigent CRP Product Summary
Assay Stability:
Onboard stability = 60 days
Calibration stability = 15 days
Precision: Total CV < 6%
Reportable Range:
CRP High sensitivity method
0.01 to 16.0 mg/dL (Conv)
0.1 to 160 mg/L (SI)
CRP Standard method
0.02 to 32.0 mg/dL (Conv)
0.2 to 320 mg/L (SI)
CRP Wide Range method
0.02 to 48.0 mg/dL (Conv)
0.2 to 480 mg/L (SI)
LOQ:
0.01 mg/dL (Conv)
0.1 mg/L (SI)
CRP Standard and Wide Range methods
0.02 mg/dL (Conv)
0.2 mg/L (SI)
Assay Method: Turbidimetric /
Immunoturbidimetric
Reagent LN: K26-30/6K26-41
Reaction Mode: Rate-Up
Calibration:
Spline
Multigent CRP Calibrator Set 6K26-10
Multigent CRP Calibrator HS 6K26-14
Multigent CRP Calibrator WR K26-12
cSystems Reagent Volumes:
CRP High sensitivity and Standard method
R1 Reagent: 100 L
R2 Reagent: 100 L
CRP Wide range method
R1 Reagent: 120 L
R2 Reagent: 120 L
Sample Volume:
CRP Wide range and Standard method: 2.0 L
CRP High Sensitivity method: 4.0 L
Acceptable specimen: Serum, plasma
REF
REF
REF
REF
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

34. Multigent CRP Product Summary
SmartWash: Assay parameters for ARCHITECT cSystems
The only SmartWash required for CRP16, CRP32 and CRP48 is a 10% Detergent B cuvette wash for Triglyceride.
This wash is not required on systems with ARCHITECT software version 7.00 and above.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

35. Q&A
Question:
How will existing AEROSET CRP customers be managed since this product is not available for use on AEROSET?
Answer:
Inventory of the existing MULTIGENT and Abbott CRP products which are labeled for AEROSET use will be managed to support AEROSET customers until retirement of the system 12/31/10.
Not for customer distribution
For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010

36. Q&A
Question:
Do we have the cardiac risk assessment claim for the high sensitivity application CRP HS?
Answer:
No, We cannot promote use outside of labeling. Refer to “Limitations of the Procedure” in the package insert. 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.
END OF DOCUMENT
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For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, , version 5
© 2010 Abbott
Multigent CRP Harmonization
September 2010