W W W. Q I A G E N. C O M Dirk Heckel, PhD Diagnostic Sample Preparation and Stabilization QIAGEN GmbH

W W W. Q I A G E N. C O M Standardizing sample preparation in 2004 QIAamp DSP Virus kit: CE certified in April 2004 BioRobot M48 for medium throghput in May 2004  BioRobot MDx: CE certification in Q3/04  BioRobot EZ1: for low throughput in Q3/04

W W W. Q I A G E N. C O M Benefits of Standardization by Automation Automation of generic sample preparation methods can lead to: Securing of result integrity Reduction of user errors Increased process control Comprehensive process documentation Medium to High throughput High level of user convenience

W W W. Q I A G E N. C O M QIAGEN’s solution for required functionality (1) Sample ID tracking Secure system setup Cross contamination free processing Automatic barcode reading of sample ID Tracking of sample ID from sample input area to result documentation Software guidance for system setup Automatic verification of complete and correct system setup (Load Check) Usage of filter tips 8-Channel Pipetting Proprietary design of robotic vacuum chamber (RoboVac)

W W W. Q I A G E N. C O M QIAGEN’s solution for required functionality (2) High Level of Process control Walk away automation Result documentation Clot Check Positive sample dispense verification Liquid detection Constant verification of key process parameters (e.g. temperature/pressure) Load check Robotic arm with lab hand and 8 Channel dispenser head RoboVac Heating/Cooling device Result file including information such as sample ID, sample validity, user, instrument, time stamp, maintenance status etc.

W W W. Q I A G E N. C O M Standardization = Verification / Validation CE-Marking requires performance evaluation of the IvD system BioRobot MDx DSP system IvD Reagents IvD Instrument Application process IvD HardwareIvD Software Hardware Module Verification Software Unit Level and Integration Level Verification Process Verification / HW/SW integration verification Chemistry Verification System Verification & Validation

W W W. Q I A G E N. C O M System Verification & Validation  Limit of detection  Linearity and linear range  Accuracy  Precision, intermediate precision, reproducibility  Robustness, whole system failure rate  Cross contamination  Clinical specificity System Verification & Validation

W W W. Q I A G E N. C O M Limit of detection QIAamp DSP 96 Virus MDx Protocol all Input Titer IU/ml nhits% , , , , , , ,67 NC1800,00 pos. control18 100,00 95% probit value123.1 confidence interval all Input Titer IU/ml nhits% , , , , , ,14 0, , ,00 pos. control42 100,00 95% Probit value confidence interval LOD HBV = 26 IU/ml  144 c/ml LOD HIV = 123 IU/ml  70 c/ml all Input Titer IU/ml nhits% , , , , , , ,67 95% probit value28.2 confidence interval16, LOD HCV = 28 IU/ml

W W W. Q I A G E N. C O M Linear range (24 replicates at 7 titer levels) COBAS AMPLICOR HBV MONITOR COBAS TaqMan HCV LCx HIV RNA Quantitative Assay

W W W. Q I A G E N. C O M Intermediate Precision HIV cont. QIAamp DSP 96 Virus MDx Protocol

W W W. Q I A G E N. C O M Robustness  Comparison of different primary tubes  4 Replicates of 13 individual donors  3 tube types per donor  Spiked w/ 1*10^5 IU/ml

W W W. Q I A G E N. C O M Standardizing sample preparation in 2004 QIAamp DSP Virus kit: CE certified in April 2004 BioRobot M48 for medium throghput in May 2004  BioRobot MDx: CE certification in Q4/04  BioRobot EZ1: for low throughput in Q3/04  BioRobot EZ1: CE certification in Q  BioRobot EZ1: CE certification of Virus Kit in Q BioRobot MDx DSP system