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Thermo Scientific Indiko Reagents for Immunosuppressant Drug Testing Complete solutions for patient monitoring The cost-effective Thermo Scientific Indiko benchtop analyzer and bar-coded reagent is designed for easy-of-use and load-up and walk-away convenience.

Thermo Scientific QMS Everolimus Immunoassay Accurate: Correlates well with gold standard methods Efficient: Excellent accuracy across assay range Rapid: Quick turn-around-time Limit Of Quantitation (LOQ): 2 ng/ml Reportable Range: 2 to 20 ng/ml Precision Control samples were tested in replicates of 2, twice per day for 20 days, yeilding a total of 80 replicates. Sample Mean (ng/ml) SD (ng/ml) % CV SD (ng/ml) Control 1 4.56 0.2 4.6 0.3 7.3 Control 2 8.67 0.3 2.9 0.4 5.0 Control 3 14.72 0.5 3.5 0.7 5.1 % CV Reference Method Comparison Hitachi vs. LC-MS/MS Sample Type N Passing Bablok Regression Correlation Coefficient (r) Kidney 150 1.11-0.005 0.96 Liver 111 0.98-0.06 0.93 Heart* 41 1.00-0.15 0.96 * Heart indication is ex-us only Another study compared QMS vs. various LC-MS/MS Method N QMS vs. System 1 124 QMS vs. System 2 124 Slope 95% CI Deming s Intercept 95% CI Slope 95% CI Passing-Bablok Intercept 95% CI 0.93 0.03 0.92 0.17 (0.87 to 0.98) (-0.41 to 0.46) (0.87 to 0.98) (-0.15 to 0.54) 1.00-0.08 1.01-0.15 (0.95 to 1.06) (-0.48 to 0.33) (0.95 to 1.08) (-0.50 to 0.17) EVEROLIMUS IMMUNOASSAY

Method Comparison Samples: 101 samples were analyzed by the Thermo Scientific QMS Everolimus Immunoassay on the Indiko vs. the reference Hitachi. Passing-Bablok Analysis: Indiko = 0.91* 0.07 with a correlation coefficient of 0.97. Indiko (ng/ml) 15 10 5 1.1 Line Deming Regr Ordering: for IVD use Item Number Description Format 10015987 QMS Everolimus Immunoassay 380005 QMS Everolimus Calibrator Set 380010 QMS Everolimus Control Set Ordering: for use in European Union R1 22 ml, R2 8 ml 6 levels, 3 ml 1 vial each 3 levels 3 ml 1 vial each Item Number Description Format 10015993 QMS Everolimus Immunoassay* 373860 QMS Everolimus Calibrator Set* 373878 QMS Everolimus Control Set* * not available in US R1 22 ml, R2 8 ml 6 levels, 3 ml 1 vial each 3 levels 3 ml 1 vial each 0 0 5 10 15 Hitachi (ng/ml)

Thermo Scientific QMS Tacrolimus Immunoassay Accurate: Correlates well with the gold standard LCMS/MS methods Efficient: Quick turn-around of patient results Convenient: liquid ready-to-use reagents Limit of Quantitation: (LOQ): 0.9 ng/ml Reportable Range: 1.0-30.0 ng/ml Precision Control samples were tested in replicates of 2, twice per day for 20 days, yielding a total of 80 replicates. Within-Run Total Sample Mean (ng/ml) SD (ng/ml) % CV SD (ng/ml) %CV Control 1 3.62 0.2 5.5 0.29 8 Control 2 13.12 0.28 2.1 0.99 7.5 Control 3 7.26 0.24 3.4 0.52 7.2 Control 4 15.09 0.48 3.2 1.2 8 Control 5 23.55 0.54 2.3 1.76 7.5 Reference Method Comparison A comparison of the data between the Beckman Coulter AU680 and the LC-MS/MS. Transplant Type Number Slope Intercept Correlation All 383 1.1 0.56 0.973 Kidney 136 1.077 0.98 0.98 Liver 133 1.127 0.21 0.963 Heart 114 1.108 0.36 0.974 Comparative Method N Slope (95% CI*) LC-MS/MS System 383 LC-MS/MS System 232 Abbott Architect Tacrolimus Assay 208 Intercept (95% CI) 1.111 0.53 (1.084 to 1.137) (0.31 to 0.76) 1.13 0.71 (1.092 to 1.167) (0.42 to 1.01) 1.126-0.03 (1.071 to 1.181) (-0.63 to 0.56) Correlation Coefficient 0.972 0.967 0.937 TACROLIMUS IMMUNOASSAY

Method Comparison Method Comparison studies were performed between the QMS Tacrolimus Immunoassay and LC-MS/MS method for 136 kidney, 133 liver and 114 heart transplant patient samples. Additional method comparison studies were performed between the QMS Tacrolimus Immunoassay and Abbott Architect Tacrolimus Assay for a total of 208 kidney and liver transplant patient samples. Results of the Deming regression analyses for the study are shown. Samples: 101 samples were analyzed by the Thermo Scientific QMS Tacrolimus Immunoassay on the Thermo Scientific Indiko vs. the reference Beckman Coulter AU680 analyzer. Deming s Regression Anaysis: Indiko = 0.92 (AU680)- 0.16255 with a correlation coefficient of 0.9914. 30 25 1.1 Line Deming Regr Indiko (ng/ml) 20 15 10 Ordering: Item Number Description Format 10015556 QMS Tacrolimus Immunoassay R1 18mL, Extraction Reagent R2 12 ml 50 ml 10015573 QMS Tacrolimus Cal Set Level A Level B-F 6 levels 4 ml, 1 vial 2 ml, 1 vial each 280-Q Rap/Tac/CsA Control Level Q* 4 ml, 4 vials 280-1 Rap/Tac/CsA Control Level 1 4 ml, 4 vials 280-2 Rap/Tac/CsA Control Level 2 4 ml, 4 vials 280-3 Rap/Tac/CsA Control Level 3 4 ml, 4 vials *Can be used for low level control for Tacrolimus. 5 0 0 5 10 15 20 25 30 Olympus AU680 (ng/ml)

Thermo Scientific CEDIA Cyclosporine PLUS Assay Accurate: Lot-to-lot consistency Efficient: Two-point calibration curve Convenient: High and low range assays use same reagents Rapid: Single lysing step sample preparation Limit of Quantitation (LOQ): Limit of Quantitation is 25 ng/ml Reportable Range: 25 to 2000 ng/ml Precision Precision Controls were run twice a day in duplicate over 20 days for a total of 80 replicates. Low Range Assay n Mean Within Run Total SD CV% SD Control Level 1 80 84.8 4.1 4.8 6.2 Control Level 2 80 186.4 4.1 2.2 10 Control Level 3 80 319.7 5.9 1.8 13.2 High Range Assay n Mean Within Run Total SD CV% SD Control Level 4 80 744.3 20.0 2.7 34.4 Control Level 5 80 1508.4 20.7 1.4 57.3 Reference Method Comparison Low Range Assay Transplant Type x-axis Linear Regression Sy.x Deming s Sy.x r n Range All HPLC-MS 0.97x + 8 1.04x - 1 26 18 0.93 311 25-437 ng/ml All EMIT 1.05x + 6 1.09x + 2 16 11 0.97 298 28-406 ng/ml Kidney HPLC-MS 1.02x - 9 1.09x - 17 24 16 0.94 122 25-437 ng/ml High Range Assay All HPLC-MS 0.97x + 98 1.01x + 71 81 57 0.97 93 486-1882 ng/ml All EMIT 1.00x + 12 1.00x + 11 28 20 0.99 343 12-1979 ng/ml Kidney HPLC-MS 0.99x + 107 1.02x + 84 82 58 0.97 47 486-1882 ng/ml *Refer to page insert for a addition information on method comparison

Method Comparison Samples: 115 samples were analyzed by the Thermo Scientific CEDIA Cyclosporine Assay on the Indiko vs. the reference Hitachi. Deming s Regression Anaysis: Indiko =1.01 (Hitachi) -2.6 with a correlation coefficient of 0.990. 500 400 1:2 Line Deming Regr CsA Hitachi (ng/ml) 300 200 100 0 0 100 200 300 400 500 HPLC-MS (ng/ml) Samples: 148 samples were analyzed by the CEDIA High Range Cyclosporine Assay on the Indiko vs. the reference Hitachi. Deming s Regression Anaysis: Indiko =1.00 (Hitachi) -1.8 with a correlation coefficient of 0.995. Low-Range Performance High-Range Performance Slope 1.01 1.00 Correlation 0.99 0.995 Intercept -2.60-1.80 Ordering: Item Number Description Format 10016283 CEDIA Cyclosporine PLUS Assay R1 41 ml, R2 19 ml includes Low Range Calibrators A & B 1 vial, 2 ml each level 100012 CEDIA Cyclosporine PLUS 2 levels, 4 ml High Range Calibrator Kit 2 vials each 100207 Cyclosporine High Range Control 2 ml, 6 vials, Level 4 diluent 8 ml, 2 vials 100208 Cyclosporine High Range Control 2 ml, 6 vials, Level 5 diluent 8 ml, 2 vials 280-Q Rap/Tac/CsA Level Q* 4 ml, 4 vials 280-1 Rap/Tac/CsA Control Level 1 4 ml, 4 vials 280-2 Rap/Tac/CsA Control Level 2 4 ml, 4 vials 280-3 Rap/Tac/CsA Control Level 3 4 ml, 4 vials *Can be used in place of Rap/Tac/CsA Level 3 Indiko (ng/ml) 2000 1500 1000 500 0 1:2 Line Deming Regr 0 500 1000 1500 2000 Hitachi (ng/ml) CYCLOSPORINE PLUS ASSAY

Thermo Scientific CEDIA Mycophenolic Acid (MPA) Assay Accurate: Correlates well with gold standard methods Efficient: Two-point linear calibration Rapid: No extraction step Limit Of Quantitation (LOQ): 0.3 µg/ml Reportable Range: 0.3 to 10 µg/ml Precision Control samples were tested in replicates of 2, twice per day for 20 days, yeilding a total of 80 replicates. Sample Mean (µg/ml) Within-Run SD (µg/ml) %CV SD (µg/ml) Total %CV Control 1 0.875 0.045 5.1 0.071 8.1 Control 2 2.840 0.055 1.9 0.083 2.9 Control 3 6.550 0.112 1.7 0.188 2.9 Ordering: Item Number Description Format 10016265 100277 100278 100279 100280 CEDIA Mycophenolic Acid Assay CEDIA Mycophenolic Acid Calibrator Set MAS Mycophenolic Acid Control 1 Kit MAS Mycophenolic Acid Control 2 Kit MAS Mycophenolic Acid Control 3 Kit R1 26 ml, R2 11 ml 2 levels, 5.0 ml 2 vials each 1 level, 5.0 ml 4 vials each 1 level, 5.0 ml 4 vials each 1 level, 5.0 ml 4 vials each

Reference Method Comparison Hitachi vs. HPLC. Sample N Heart 96 Kidney 92 All 188 Regression Method Least Square Deming Slope Intercept Slope Intercept 1.114 0.20 1.147 0.12 (1.061 to 1.166) (0.05 to 0.36) (1.094 to 1.200) (-0.04 to 0.28) 1.127 0.16 1.060 0.06 (0.974 to 1.080) (-0.03 to 0.36) (1.006 to 1.113) (-0.13 to 0.25) 1.054 0.22 1.089 0.12 (1.015 to 1.092) (0.09 to 0.34) (1.051 to 1.128) (-0.01 to 0.25) r 0.974 0.971 0.968 Method Comparison A total of 188 pre-dose samples from adult transplant patients receiving mycophenolate mofetiel or mycophenolate sodium therapy were tested in a method comparison study using LC-MS/MS as the reference method. The table below summarizes the results of the study showing separate analysis by transplant type and together using EP Evaluator. In the regression method column, the slope and intercept results are presented with 95% confidence intervals in parentheses. Samples: 115 samples were analyzed by the CEDIA Mycophenolic Acid Assay on the Indiko vs. the reference Hitachi. Deming s Regression Anaysis: Indiko = 1.02 (Hitachi)-0.01 with a correlation coefficient of 0.968. 10 1.1 Line Deming Regr 8 Indiko (ug/ml) 6 4 2 0 0 2 4 6 8 10 Hitachi (ug/ml) MYCOPHENOLIC ACID (MPA) ASSAY

Thermo Scientific CEDIA Immunosuppressant drug testing One of the most effective therapies for patients with endstage organ failure is solid organ transplantation. Typically, one or more immunosuppressive drugs (ISD) are used to prevent rejection of transplanted organs and tissues. Periodic measurements of a drug s concentrations are performed to allow physicians to make adjustments to the patient s drug therapy, ensuring long-term success. Immunosuppressant drug monitoring can be done by several methods; the most common is immunoassay. We offer the most comprehensive menu of Immunosuppressant Drug Management assays which are recognized worldwide for their ease-of-use, quality, performance, and lot-to-lot consistency. Full ISD menu on a single analyzer Convenient on-site testing Improved laboratory efficiency and turnaround time Flexibility in instrument placement Description CEDIA Cyclosporine PLUS Assay QMS Tacrolimus Immunoassay CEDIA Mycophenolic Acid Assay QMS Everolimus Immunoassay Sample Type Whole blood Whole blood Plasma Whole blood Thermo Scientific Indiko analyzer and immunosuppressant drug monitoring Thermo Scientific Indiko, together with a complete menu of immunosuppressant drug monitoring assays, provides an excellent solution for patient monitoring. Indiko allows for patient testing at a monitoring site improving turnaround time and enabling doctors to make critical decisions sooner. The Indiko benchtop analyzer also provides a single platform solution for all Thermo Scientific ISD immunoassays, improving laboratory efficiency. The continuous access allows for samples and reagents to be added without interrupting the testing process. Indiko is a fully automated bench top analyzer for clinical and specialty testing Indiko is an easy-to-use, cost-effective system designed for load-up and walk-away convenience. Intuitive user interface and many automated features help to manage the daily workflow. The self-contained Indiko, with its small footprint, fits ideally with laboratory space limitations. IMMUNOSUPPRESSANT DRUG TESTING

The compact Indiko requires very little space Flexible, easy operation Intuitive user interface with touch-screen option Streamlined information management with various reporting options, and advanced result inventory management A mix of sample cups and barcoded primary tubes can be used Automatic start-up protocol Loadable application data and calibrator and control values True walk-away analysis Different sample types can be analyzed at the same time Real-time QC program with multiple Westgard rules Continuous access to samples, reagents and cuvettes without interrupting the testing process Up to two hours walk-away time Cost-effective solution Unique, low-volume cuvette technology Very low volume of samples (2 to 120uL) and reagents (2 to 240uL) result in overall low waste Real-time QC program assures reliable performance Minimal daily maintenance maximizes analyzer uptime Water consumption: 1.5 liter/hour

Instrument Specifications Capacity Dimensions & Weight Power Supply Average Noise Level at 1 meter Deionized Water Consumption Environmental Conditions Regulatory Filter Measurement Temperature 37 ºC Light Source Absorbance Range Reaction Vessels On-board Capacity Thermo Scientific Indiko Up to 200 tests per hour for 1 reagent assays, approximately 100 tests per hour for 2 reagent assays 29.5 in / 75 cm (W) x 27.6 in / 70 cm (D) x 24.4 in / 62 cm (H), 51 in / 130 cm (H) with cover open, 187 lbs / 85 kg 100-240 V ± 10%, 50-60 Hz, ± 5%, 250 W < 60 db (A) 1.5 liters/hour Operating temperature range 18 to 30 ºC, humidity 40-80% (non condensing) Confirms with CAN/CSA-C22.2 No. 61010-1-04 FDA clearance, 510(k) number: k110035 (Indiko 9836000) 98/79/EC IVD MD Directive 340-700 nm Flash Lamp Reaction End Volume 120-300 µl Samples & Reagents On-board Capacity Sample Volume Size 2-120 µl Sample Containers Sample Barcode Reagent Volumes 2-240 µl Reagent Containers 0-3.5 A, resolution of 0.001 A and reproducibility of SD <0.005A at 2A 360 measurement cells - 36 cuvettes with 10 reaction cells each, up to 2 hour walk-away time, depending on workload Maximum 6 racks - 9-position sample rack or 6-position reagent rack in disk cooled about 8 ºC below ambient temperature, depending on workload 0.5 ml, 2.0 ml cups and sample tubes (diameter 12-16 mm, length 75-100 mm) Code 128 and barcodes USS Codabar, Interleaved 2 of 5 and Code 39 with a check digit 10 ml and 20 ml vials Sample & Reagent Dispensing CV 2% for volumes 2 µl Calibration Data Management Factor, bias, linear, logit-log, spline, polynomial & point-to-point calibration Windows -based workstation - data input online, via mouse, keyboard, barcode reader, and touch screen (optional) Thermo Scientific Indiko Plus Up to 350 tests per hour for 1 reagent assays, approximately 200 tests per hour for 2 reagent assays 37 in / 94 cm (W) x 27.6 in / 70 cm (D) x 24.4 in / 62 cm (H), 51 in / 130 cm (H) with cover open, 242 lbs / 110 kg 100-240 V ± 10%, 50-60 Hz, ± 5%, 300 W < 60 db (A) 2.5 liters/hour Operating temperature range 18 to 30 ºC, humidity 40-80% (non condensing) Confirms with CAN/CSA-C22.2 No. 61010-1-04 FDA clearance, 510(k) number: k110035 (Indiko Plus 98640000) 98/79/EC IVD MD Directive 340-700 nm 37 ºC Flash Lamp 0-3.5 A, resolution of 0.001 A and reproducibility of SD <0.005A at 2A 360 measurement cells - 36 cuvettes with 10 reaction cells each, 1 to 3 hour walk-away time, depending on workload 120-300 µl 54 samples - 9-position sample rack, max 6 racks; 42 reagents in disk cooled about 8 ºC below ambient temperature, depending on workload 2-120 µl 0.5 ml, 2.0 ml cups and sample tubes (diameter 12-16 mm, length 75-100 mm) Code 128 and barcodes USS Codabar, Interleaved 2 of 5 and Code 39 with a check digit 2-240 µl 10 ml and 20 ml vials CV 2% for volumes 2 µl Factor, bias, linear, logit-log, spline, polynomial & point-to-point calibration Windows -based workstation - data input online, via mouse, keyboard, barcode reader, and touch screen (optional) Consumable Ordering Information Part Number Description Kit Configuration 986000 TENCELL cuvettes 1 box (10,800pcs) 989220 0.5 ml sample cups 1000 pcs 989221 2 ml sample cups 1000 pcs 984050 10 ml reagent bottles 5 pcs 981456 20 ml reagent bottles 16 pcs SP06662 Reagent rack 3 pcs SP06666 Sample rack 6 pcs 984030 Washing solution 4.5% 4 x 20 ml 981712 Tubing maintenance solution 6 x 20 ml thermoscientific.com/diagnostics 2014 Thermo Fisher Scientific Inc. All rights reserved. Copyrights in and to portions of the illustrations are owned by a third party and licensed for limited use only to Thermo Fisher Scientific by Getty Images. CEDIA is a registered trademark of Roche Diagnostics. Beckman Coulter is a registered trademarks of Beckman Coulter, Inc. Windows is a registered trademark of Microsoft Corporation. All other trademarks are the property of Thermo Fisher Scientific and its subsidiaries. Information and technical specifications are subject to change without notice. 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