Carr UniFuge Single-Use Separation System

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UniFuge Single-Use Cell Harvesting Technology CONFIDENTIAL New Product Update UniFuge Single-Use Cell Harvesting Technology CONFIDENTIAL

Design Objectives Robust, single use cell harvesting centrifuge Scalable platform Harvest capacity of 10L to 2,500L bioreactor Pilot ≈ 3L/min with1.5L cell volume collection Production ≈ 20L/min with 40L cell volume collection Gamma irradiated single use liner Fully automated processing High recovery of cells with minimal cell lysis Process rates allow for single shift harvesting CONFIDENTIAL INFORMATION DISCLOSURE FOR ‘A’ The information contained in this document contains privileged and confidential information.  It is intended only for the use of the person(s) named above. If you are not the intended recipient,  you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited.

UniFuge® Concept, Prototype & Testing Dec 2007 - Concept Mar. 2009 – Alpha unit mammalian cell test Oct. 2009 – Beta unit field trials begin Alpha Prototype Beta Prototype

UniFuge® Design Concept Solid Bowl Centrifuge Reinforced & contained flexible single-use component Semi-continuous, automated cell processing Programmable feed & harvest cycles Intermittent cell concentrate removal Closed loop operation Gamma irradiated disposable liner Sterile connections for feed, centrate & concentrate Rotating mechanical seal, no process contact CONFIDENTIAL INFORMATION DISCLOSURE FOR ‘A’ The information contained in this document contains privileged and confidential information.  It is intended only for the use of the person(s) named above. If you are not the intended recipient,  you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited.

UniFuge® Single Use Component Rigid + flexible components Tube set is integrated as part of single use component Terminally sterilized (gamma) Complies with: ISO 10993 USP <87> & <88> Class VI plastics Polycarbonate Polyurethane Polypropylene C-Flex Silicone

Automatic pinch valves UniFuge® Overview Automatic pinch valves Ultrasonic sensor Feed In Concentrate Out Supernatant Out Peristaltic feed & harvest pump Single-use pressure sensor Onboard air supply and sterile filter Fiber optic level sensor Cooling jacket supply connect RPM Sensor

UniFuge® Automated Processing Auto & manual modes Setup integrity test mode Controlled parameters Bowl speed / G-force Feed flow rate Fill volume (flow rate / time) Cycle time Discharge time Number of cycles Monitored Parameters Supernatant line pressure Air pressure Vibration (accelerometer) Calibration screens Alarms

UniFuge® Pilot Layout Process connections: 57” (1448mm) 25” (635mm) Process connections: Electrical: 230VAC, 1 phase, 50/60Hz, 15A Feed supply: up to 4Lpm, ½” weldable tubing Cell concentrate discharge: ½” weldable tubing Supernatant discharge: ½” weldable tubing Cooling (optional): ¼” FNPT 4LPM @ 70KPA; -25° to´+20° C

UniFuge® Pilot Prototype

UniFuge® Pilot Prototype

UniFuge® Development Tests Alpha Unit 3/4/09 Objective: separation performance 20L CHO Cells Feed: 1.15x106 cells/ml @ 95% viability Three tested conditions 1, 2 & 3 L/min 2,000 x g Cell Capture Results 1 L/min: 99.99% 2 L/min: 99.8% 3 L/min: 98.6% Beta Unit 8/26/09 Objective: separation performance, lysis, viability 20L SF9 Cells Feed: 6x106 cells/ml @ 73% viability Three tested conditions 1, 2 & 3 L/min 2,000 x g Cell Capture Results 1 L/min: 99.99% 2 L/min: 99.9% 3 L/min: 98.8% CONFIDENTIAL INFORMATION DISCLOSURE FOR ‘customer’ The information contained in this document contains privileged and confidential information.  It is intended only for the use of the person(s) named above. If you are not the intended recipient,  you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited.

UniFuge® Supernatant Separation Results CONFIDENTIAL INFORMATION DISCLOSURE FOR ‘customer’ The information contained in this document contains privileged and confidential information.  It is intended only for the use of the person(s) named above. If you are not the intended recipient,  you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited.

UniFuge® Prototype Turbidity CONFIDENTIAL INFORMATION DISCLOSURE FOR ‘customer’ The information contained in this document contains privileged and confidential information.  It is intended only for the use of the person(s) named above. If you are not the intended recipient,  you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited.

UniFuge® Pilot Customer Field Trails Customer Trial #1 – preliminary results, awaiting formal summary Objective: Harvest with recovery of viable cells Cell Line Volume Flow rate G-force Feed Viability Harvest Viability % Loss in supernatant CHO 56L 3 L/min 2,000 99% ~98% 1.68% 50L 4 L/min 3,000 95.4% 97.3% Negligible 57L 5 L/min 98.6% 98% 2.97% 90L 96.2% - CONFIDENTIAL INFORMATION DISCLOSURE FOR ‘customer’ The information contained in this document contains privileged and confidential information.  It is intended only for the use of the person(s) named above. If you are not the intended recipient,  you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited.

UniFuge® Pilot Customer Field Trails Customer Trial #2 – preliminary results, awaiting formal summary Objective: Clarification & Harvest from Wave Bag BR Cell line Batch size Flow rate Concentrations Feed Concentrate Supernatant CHO 10L 1 Lpm 3.03x106 21.2x106 .003x106 Sf9 Baculovirus infected 4.1x106 17.91x106 .049x106 CONFIDENTIAL INFORMATION DISCLOSURE FOR ‘customer’ The information contained in this document contains privileged and confidential information.  It is intended only for the use of the person(s) named above. If you are not the intended recipient,  you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited.

 UniFuge® Summary Benefits Centrifugation Single Use Technology Improved separation performance means less downstream processing Better suited for high titers – no blinding or fouling of filters Single Use Technology Lower cost due to less cleaning/sterilization - No CIP/SIP required Less product losses due to contamination Programmable automatic processing Variable separation force Optimize feed flow rates Programmable harvest cycle time Capable of recovering and concentrating viable cells Reduced downstream filtration Scalability, Pilot -> Production 

UniFuge® Next Steps Unit(s) available for field testing in US and Europe Typical field trial period is for one (1) week and includes on site technical support Each customer will purchase the disposable liner(s) needed for testing The beta test single-use components will not be gamma irradiated Unifuge Pilot is available for sale, estimated delivery is 12 weeks