Logistics: Customer & Regulatory Expectations versus Daily Reality Marian Desmet Benoît Cloquet

B&Cemo Conf/MD/26-Jan-2006/Slide 2 1.Logistics: What is it? Total process of moving goods from a Manufacturer to a Customer in the most timely and cost-efficient manner possible Handling and movement of inbound raw materials and other supplies as well as outbound physical distribution Organisation of any project or operation, including transportation and housing

B&Cemo Conf/MD/26-Jan-2006/Slide 3 2. Clinical Research Regulatory Compliance YES! Safe & Effective

B&Cemo Conf/MD/26-Jan-2006/Slide 4 Patients CT Subjects Declaration of Helsinki/ Hippocratic Oath Good Medical Practice GCP … Contract CT Protocol Good Lab Technical Working Principles National Regulations (e.g. GBEA) Norms (CAP, ISO) 2. Clinical Research Regulatory Compliance

B&Cemo Conf/MD/26-Jan-2006/Slide 5 3.Regulatory & Customer Expectations What do they expect? Compliance? With what? Really mandatory for a company as B & C International? Differences between Customers Different viewpoints & auditing focus between Auditors

B&Cemo Conf/MD/26-Jan-2006/Slide 6 4.Compliance Approach Risk Management Approach? Risk for Regulatory Authority Inspections? Yes Are the data & systems in support of regulatory submissions? Integrate principles of GCP and related applicable regulations, incl. validation

B&Cemo Conf/MD/26-Jan-2006/Slide 7 5. Compliance Examples Laboratory Kit - Tube missing - Expired product in tube - Not delivered at right time QC Error Delay Customs Impact on Result &/or Clinical Trial? -Some tests not performed -Reliable result? - Test out-of Protocol required time-window

B&Cemo Conf/MD/26-Jan-2006/Slide 8 5. Compliance Examples Specimen Storage - 1X/day temperature monitoring - No traceability of removal in- & out in case of specimen transfer (defrosting, cleaning) Impact on Result &/or Clinical Trial? -Evidence of specimen storage at appropriate conditions at all times (incl. Transfer)?

B&Cemo Conf/MD/26-Jan-2006/Slide 9 6. Transport Validation Approach at B & C Pre-testing - Time of ambient specimen to become - refrigerated - frozen at -20°C - frozen at -80°C - In-house TempTale Validation - IQ/OQ/PQ: 1 hour temp. recording - Inter-TempTale Variability: Accuracy Static Testing: Controlled Conditions Dynamic Testing: Life Transport Test

B&Cemo Conf/MD/26-Jan-2006/Slide Transport Validation Approach at B & C: Inter-TempTale Variability N = 18 Temptales Consecutive conditions Test: 4 1/2 h 1 H 30’1 H Room T°2 – 8°C-20°C-80°CRoom T°

B&Cemo Conf/MD/26-Jan-2006/Slide Transport Validation Approach at B & C: Inter-TempTale Variability

B&Cemo Conf/MD/26-Jan-2006/Slide Transport Validation Approach at B & C: Static Test Specimens: 9 (3 X 3) Tubes filled with water Additive for “Position” in shipment container Labelling for original condition - Refrigerated - -20°C - -80°C Probe from TempTale inside tube Shipment container: TempTale sensor on Top / Middle / Bottom

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B&Cemo Conf/MD/26-Jan-2006/Slide 15 Results: Specimen T° at bottom: Stable The less dry ice surrounding the specimen, specimen T° Effect of opening/closing box on specimen T°: Almost nihil Box T° “Top”: - 45°C to - 20°C (evaporation dry ice) 6. Transport Validation Approach at B & C: Static Test 0’ 5 ½ D 0’ 5 ½ D

B&Cemo Conf/MD/26-Jan-2006/Slide Transport Validation Approach at B & C: Dynamic Test Main Objective: Verification of Life Transport Conditions - 2 specimens (tube with water) - TempTale inside tube - Shipment container: TempTale on Top / at Bottom

B&Cemo Conf/MD/26-Jan-2006/Slide Lessons Learned - Conclusions Added value of Transport Validation -Not the opening of transport boxes important, but the level of dry ice -If specimens need to remain at -80°C, they should be permanently surrounded by dry ice -Specimens half in/half out dry ice: T° variation between -80°C to -45°C