ARCHITECT cSystems & AEROSET System QUANTIA Alpha-1-Acid Glycoprotein (AGP) 6L34-40 US Only Launch: June 2010 REF Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28 version 1

Not for customer distribution 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, 3.6.28, version 1

QUANTIA A-1-AGP Launch Strategy The QUANTIA assays are available for use on the AEROSET and ARCHITECT cSystems. Assay will be available in the US only. Latin America and Canada are considered ex-US for this product. There are no differences in the application or formulation between the U.S. and non-US products. Complaint handling: Abbott has responsibility for initial complaint registration. BioKit (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, 3.6.28, version 1

Assay Disk Information Alpha-1-Acid Glycoprotein parameters (AGP, Assay 2912) are available on the following recently released ARCHITECT cSystems assay disks. Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

Assay Disk Information There will be no AEROSET assay disk available. 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, 3.6.28, version 1

Not for customer distribution Clinical Utility A-1-AGP (orosomucoid) is an “acute phase” protein. The concentration of A-1-AGP changes in response to trauma. Acute-phase proteins are rich in carbohydrate and are synthesized by the liver. Decreased levels of A-1-AGP are associated with: Estrogen therapy Severe hepatic damage Nephrotic syndrome Malnutrition Pregnancy Source(s): Quantia A-1-AGP 6L34 Package Insert, FBR Guide Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

Not for customer distribution Clinical Utility Increased A-1-AGP levels are associated with: Trauma Inflammation Infection Rheumatoid arthritis Chronic renal failure Corticosteroid therapy Cancer Pneumonia Major surgery Source(s): Quantia A-1-AGP 6L34 Package Insert, FBR Guide Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Reaction & Methodology Step 1: Sample containing A-1-AGP is added to Reagent 1 (Reaction Buffer and polyethylene glycol (PEG)). Step 2: Reagent 2 containing Antibody (anti-human A-1-acid glycoprotein goat serum) is added to the sample/Reagent 1 mix. Sample/ Reagent 1 Reagent 2 Y Y Y Y Y + Y Y ↑ A-1-AGP Specific Antibody ↑ A-1-AGP Step 3: When sample containing A-1-AGP 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 A-1-AGP in the sample. This is determined by measuring the decrease of transmitted light caused by the aggregates at a wavelength of 700 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, 3.6.28, version 1

Quantia A-1-AGP methodology Turbidimetric/Immunoturbidimetric This assay is not available on CAP proficiency surveys. Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Sample Handling Specimen Requirements: Serum Gel separator tubes have not been tested. There is no specification for tube type (glass or plastic) Plasma Acceptable anticoagulant – sodium heparin Others anticoagulants have not been tested Gel separator tubes have not tested Sample Volume = 2.0 L Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Sample Handling Specimen storage: *Guder WG, da Fonseca-Wollheim F, Heil W, et al. The Quality of Diagnostic Samples. Darmstadt, Germany: GIT Verlag; 2001:13-14. 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 5 months 1 year Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Reagent Handling Reagent Kit Configuration 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 – 35 days (840 hours) REF 6L34-40 Kit Configuration R1 1 x 50 mL R2 1 x 9 mL 170 tests/kit Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Calibration Calibration interval is 35 days (840 hours) Use the QUANTIA PROTEINS Calibrator 6K45 – 02 Calibration: Uses a water blank and the five levels of QUANTIA PROTEINS Calibrator. REF Name Size Protein Calibrator 1 1 x 1 mL Protein Calibrator 2 Protein Calibrator 3 Protein Calibrator 4 Protein Calibrator 5 Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Calibration Do not freeze calibrators. The calibrators are prepared with purified human A-1-acid glycoprotein. Calibrator values are determined and traceable to the International Reference Material CRM470. The concentration of the calibrators are indicated on the QUANTIA PROTEINS Calibrator value sheet. Calibrators are liquid ready to use and stable until the expiration date indicated on the package when stored at 2-8 °C. Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Calibration Curve – ARCHITECT cSystems Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Calibration Curve - AEROSET Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Quality Control Uses the QUANTIA PROTEINS Control, 6K53-21 QUANTIA PROTEINS Control, List No. 6K53-21 contains: This is the only control approved for use with this assay. REF Control Product Name Configuration Control I Low Level (lyophilized) 3 x 1 mL Control II High Level (lyophilized) Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Quality Control The multi-constituent controls are prepared from human sera containing A-1-acid glycoprotein, alpha-1-antitrypsin, β2-Microglobulin, with gentamicin sulfate as a preservative. The concentrations are indicated on the corresponding QUANTIA PROTEINS Control value sheet. The lyophilized controls should be reconstituted with 1 mL of deionized water or equivalent. The lyophilized controls are stable until the expiration date on the label if stored at 2-8 °C. Once reconstituted, the controls can be used for 15 days if stored between 2-8 °C. Do not freeze controls. Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Performance Data Serum and Plasma Normal Expected Range (adults): 50 to 120 mg/dL (0.5 to 1.2 g/L) Reportable Range: 15.0 to 250.0 mg/dL (0.15 to 2.50 g/L) 15.0 to 2500.0 mg/dL (0.15 to 25.00 g/L) using the on-board dilution protocol Limit of Quantitation (LOQ) = 15.0 mg/dL (0.15 g/L) LOQ represents the lowest measurable concentration at which the CV < 20% and the recovery is within +/- 20% of expected value. Limit of Detection (LOD) = 2.5 mg/dL (0.03 g/L) LOD is defined as the mean concentration of an analyte-free sample + 2SD, where SD is the within-run standard deviation. Note: SI units are g/L. To convert results from mg/dL to g/L, multiply by 0.01. Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Interference Interference studies were conducted using an acceptance criteria of +/- 10% deviation from the target value: Interfering Substance Interferent Concentration Target (mg/dL) Observed (% of Target) Lipemia 2.3 AU/cm at 660 nm 93.3 98.3 Triglycerides 1327 mg/dL (14.99 mmol/L) 87.0 101.9 Bilirubin 19.4 mg/dL (331.74 µmol/L) 90.6 100.1 Hemoglobin 523 mg/dL (5.23 g/L) 86.0 100.8 Rheumatoid factor 800 IU/mL (800,000 U/L) 91.2 103.2 Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Precision Representative data from precision study are summarized below. See Q&A slide 26 for control levels used. The precision acceptance criteria for the A-1-AGP assay is < 6% Total CV. Representative Data LEVEL N Concentration Mean (mg/dL) CV (%) Within Run Total Control Level 1 50 39.8 1.4 1.6 Control Level 2 83.3 0.6 4.1 Control Level 3 119.5 1.5 Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Method Comparison Serum results from the Quantia A-1-AGP assay on an ARCHITECT cSystem were compared with the results on the AEROSET system. Serum results from the Quantia A-1-AGP assay on an AEROSET system were compared with results on Dade-Behring BN II. ARCHITECT cSystem vs. AEROSET AEROSET vs. Comparative Method N 111 Y – Intercept 3.1 11.1 Correlation Coefficient 0.9957 0.9929 Slope 0.990 0.874 Range (mg/dL) 37.6 – 357.0 38.5 – 378.0 Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Product Summary Assay Method: Turbidimetric / Immunoturbidimetric Reagent LN: 6L34-40 Reaction Mode: End-Up Calibration: Linear QUANTIA PROTEINS Calibrator 6K45 -02 cSystems Reagent Volumes: R1 Reagent: 200 L R2 Reagent: 45 L Water: 45 L AEROSET Reagent Volumes: Water: 20 L Sample Volume: 2.0 L Acceptable specimen: Serum, plasma Assay Stability: Onboard stability = 35 days Calibration stability = 35 days Precision: Total CV < 6% Reportable Range: 15.0 to 250.0 mg/dL (Conv) 0.15 to 2.50 g/L (SI) LOQ: 15.0 mg/dL (Conv) 0.15 g/L (SI) LOD: 2.5 mg/dL (Conv) 0.03 g/L (SI) REF REF Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Product Summary SmartWash: Assay parameters for ARCHITECT cSystems Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

QUANTIA A-1-AGP Product Summary SmartWash: Assay parameters for AEROSET System Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1

Not for customer distribution Q&A There are only 2 levels of Quantia controls, what sample was used for the 3rd level in precision testing? A 1:1 mixture of Level 1 and Level 2 was used to create a third level for this testing. END OF DOCUMENT Not for customer distribution For information only unless accompanied by the Lotus Notes form that contains electronic signatures. c8000 Project Notebook, 3.6.28, version 1