QuantaSep ® Scale Up Sanitary Automated Chromatography Systems

Sepragen Corporation Why Automate your Chromatographic process Decrease down time Increase productivity Decrease time to market Consistency in performance Complete documentation GMP and GLP Regulations Economics 2

Sepragen Corporation 3 System Specifications

Sepragen Corporation Lab Quantasep Product Line 4 0 Quantasep 100 (100ml/min max flow) Quantasep 1000 (1000ml/min max flow) Hardware Feature Set: Two Pumps (Rotating Piston, positive displacement) 12 inlets and 10 fractions 3 columns Forward flow, reverse flow and bypass UV, pH, temp and Conductivity detection Sensors for pressure, air, leak and rpm check Stainless Steel Fluid-handling compartment Biocompatible materials of construction Outputs for remote data logging Fraction collector interface trigger Emergency pause Integrated, bench top, rugged, sanitary- Roche, Amgen, Lonza, SAFC, Hyclone, Invitrogen, Siemens

Sepragen Corporation cGMP Pilot and Production QuantaSep Sanitary, Bio-compatible Systems at Schering Plough, Teva, Baxter, Dyax 5 QuantaSep® 100 QuantaSep® 1800 QuantaSep® 5000 QuantaSep® 1000LX QuantaSep 1800: 1800 ml/min QuantaSep 5000: 5L/min QuantaSep 1000 LX: 2 in one 100ml/min & 1000ml/min QuantaSep 10000: 10L/min Compact foot print; no metals;removal tubing; low system volume

Sepragen Corporation Custom, Sanitary, Liter per minute Class 1 Div 2 Skids Custom Quantasep Process Chromatography Skids 5LPM & 30 LPM SKIDS at Human Genome Sciences

Sepragen Corporation Gradient 2 Pump Liter per minute per pump, 5-95% Gradient 10 Inlets, 2 Outlets, Filter, Bubble Trap, Column fwd, Rev & Bypass Pre and post column pH and Cond sensors, Multi wavelength UV Sanitary 316L SS Piping, 304 SS Moblie Ex Proof Skid Air sensor, Auto air removal and Bubble Trap with control system Leak sensor, Pressure Sensor Filter, Flow through and Bypass CE, BASEEFA (class 1 Div1, T4) Certified ATEX explosion proof skid Quantasep Process Chromatography Skids at GSK, Novartis, Neose

Sepragen Corporation Dramatic Space savings with Quantasep 8 QuantaSep GE Bio-Process 3mm skid

Sepragen Corporation 9 System Selection vs. Column Size

Sepragen Corporation 10 Purification of MAb onQuantasep100 A simple, load, wash elute and strip Ab isolation using Protein A Column

Sepragen Corporation Critical Software features nIntuitive method builder nDashboard Control nComprehensive run documentation and report 11

Sepragen Corporation Quantasep Software Feature Set 12 Win XPbased computer control Easy point & click interface Auto & manual operation Method builder and editor Chromatogram and analysis Event and alarm log Easy software calibration GMP Reports Part 11 Compliance

Sepragen Corporation Software module for Quantasep Systems Capabilities Real time point& click process control Data acquisition Analysis FDA compliant Reports reports

Sepragen Corporation Manual gradient

Sepragen Corporation Qsep Auto Gradient Run

Sepragen Corporation 16 P&ID with pre-column filter and sensor options Active Air Trap Multimode detector Pre column Multimode detector Advanced Gradient System Pre column filter Positive displacement pump Fraction Collection valves Column hookup with forward and reverse flow capability Column Pressure Filter pressure Inlet Buffers

Sepragen Corporation Chromatogram Manipulation And Instant Data Analysis 17 Gradient Overlays Instant Data Analysis (buffer consumption etc. during elution

Sepragen Corporation Chromatogram and data analysis 18

Sepragen Corporation Peak Identification and analysis

Sepragen Corporation Intuitive Method Builder nTabular format - eliminates the hassle of programming nPick and choose method steps for unprecedented control nAutomatic method validation 20

Sepragen Corporation Software Features Easy operation, monitoring& control Operation from graphical P&ID screen Manual or Automated Modes Real-time Chromatogram Programmable based on time, volume or sensor values Real time event log Real time alarms 21

Sepragen Corporation Reports nValidation 4track alarms, events, notes and any manual changes nAutomatic analysis report nCalibration Report 4Calibration data 4Time between calibrations nMethod and column information 22

Sepragen Corporation Calibration History and Report 23

Sepragen Corporation More Software Features Password controlled security system Chromatogram replay and zoom capabilities Linear or step gradient programmability Generic file formats for easy export Settable alarm conditions Built-in audit tracking capability 24

Sepragen Corporation 25 Product Features and Benefits

Sepragen Corporation 26 Differentiating Features  Hardware –Fully Integrated system –Compact foot-print –Real time air ejection –Leak Detect – multimode detector –Pump stall feed-back  Software –Intuitive method builder –Easy P&ID Control –Comprehensive reports –Chromatograms & analysis

Sepragen Corporation Precision Rotary piston pumps with stepper motor control 27 Positive displacement Stepper motor control No check valve for good clean-ability Low pulsation Small displacement/ rev= even flow

Sepragen Corporation 28 Gradient Performance- 100:1 Turn down ratio on pumps

Sepragen Corporation Real- time Air Ejection Vs. Passive Bubble Traps nProtects against dilution of Product nNo Unnecessary Gradient formation nProvides Protection of Column from any amount of air nCan be used to detect end of sample 29 Causes Dilution of Product Unwanted Gradient formation Doesn’t provide complete protection of column against air Increases Holdup volume Air Outlet Flow In Flow Out 3 way valve Ultrasonic air sensor Manual air valve Air Flow in Flow Out Active Air EjectionPassive Bubble Trap

Sepragen Corporation 30 With Active Air Trap 0.25L elution volume With Standard Bubble Trap 0.4L elution volume Active Air Trap reduces Elution Volume by 50%

Sepragen Corporation 31 Cleaning Validation Sanitization Study Process: Inoculate Incubate Wash in NaoH Water Wash Swab at test points

Sepragen Corporation 32 Results of Microbial challenge study on Quantasep 1000 LocationS. AureusE.ColiP.Aerg.C. AlbicansA.niger Inlet A00000 Inlet B00000 Pump A00000 Pump B00000 Manifold A00000 Manifold B00000 Pressure00000 Mixer00000 Col Outlet00000 Col. Inlet00000 Bypass In00000 Bypass Out00000 UV flow cell00000 Cond. sensor00000 pH sensor00000 pH Ref00000 Fraction comm00000 Fraction Air Outlet00000 Air Inlet00000

Sepragen Corporation 33 Material Tubing Silicone, polyethylene and polypropylene, 316L ss Valves Polypropylene, PTFE diaphragms, 316L SS Pump Head Ceramic, 316LL SS Pump Body PVDF, 316L SS Instrumentation glass/quartz/316L stainless steel Gaskets Silicone, EPDM Material of Construction

Sepragen Corporation Multimode Detector Vs. Individual Detectors UV, pH, Conductivity and Temp. all in one Reduce Lag time between detectors Minimize Hold up / Dead zone More accurate control of Chromatography process Separate UV, pH, Conductivity and Temp. Too much lag time between detectors. Increases unnecessary Hold up / Dead Zone. Harder to control and validate a process. 34 Multimode DetectorSeparate Detectors Flow in Flow out All Sensors are embedded in one unit Separate detector flow cells connected by tubing Flow in Flow out

Sepragen Corporation Chromatography Automation Cost-benefit analysis Overall cost with system – Fixed Cost: System and accessories- manual components – Variable Cost: annual maintenance Benefits – Direct Saving Labor Savings in production: Skilled labor (upto $400/hr fully burdened) Labor Savings in documentation, report writing and admin – Indirect Savings Better time management with 24/7 operation Lesser skilled labor rate can be applied to production Improvement in lot-to-lot consistency or quality Reduced batch failure Accessible documentation for regulatory compliance 35

Sepragen Corporation Cost- Benefit Case Study 36 Incremental investment $258K Savings/run=25 hrs or$400x25= $10K/run=$30K/mo Payback= 258/ 30 x12 =7 mos

Sepragen Corporation 37 Competitive Analysis

Sepragen Corporation Product Comparison– Qsep 100 vs AKTA Explorer 38 System PositioningSolution/ Price QuantaSep 100 is also positioned as small scale production system (simple, compact, Integrated unit design)  Small scale production  Process scale up studies  Integrated design with certain options  Simpler selection  Priced 10-15% lower than competition  Better features AKTA Explorer is positioned as “all things to all people” tool  Small scale production tool  Process scale up studies  R&D  QC  Price10-15% above Qsep 100  Modular design with “mix and match” of different components  Complex selection criteria

Sepragen Corporation Advantage: QuantaSep 100 over Akta Explorer FeaturesQsep 100 Akta Exp Quantasep Advantages Hardware Low System Backpressure at max-flow YesNoAkta generates high pressure at 100 ml/min; Qsep is only 50% of the pressure Can Run Pump DryYesNoPumps need to be primed or doesn’t flow Pumps don’t siphonYesNoUnintended loss of buffer or sample Auto Air Eject SystemYesNoColumn protected from air intrusion Leak detectionYesNoProtection from loss of material Diaphragm valvesYesNoDiaphragm valves are more sanitary compared to rotating valves Sanitary designYesNoSanitary tubing connections; Bug Challenge study Software Easy to use and programYesNo2 hrs to learn software as opposed to 2 days Point & Click P&ID operation YesNoEasy to run, monitor and change parameters Real time analysisYesNoReal time superior process control Get buffer volumes; switch conditions; % areas in real time as opposed to post run 39

Sepragen Corporation Similarities between QuantaSep 100 vs Akta Explorer FeaturesQsep100AktaOptions Bench topYes Similar footprint Flow rate ml/min Similar stated flow range but Akta’s usable flow range is ~40 ml/min Air detectoryes Akta uses it to stop flow not remove air dynamically Gradient0- 100% Similar Sample injectoryes In Quantasep sample loops are standard DetectorsUV, Cond, pH All 3 sensors standard Pumps222 Pumps but Akta pumps can only run with primiing Columns31Quantasep can enable user to do uf/df Manual & Auto OperationYes Buffer selection; Flow setting; switch conditions based on time, volume, UV, pH, Cond, Air, Fraction collection SecurityYes Controlled access Data AnalysisYes % areas; HETP; buffer usage; switch conditions ReportsYes Method and batch; chromatogram; alarms & events; access 40

Sepragen Corporation Product Positioning – Sepragen Qsep 1000 vs. GE AKTA Pilot 41 System PositioningSolution/ Price QuantaSep 1000 is also positioned as small scale production system (simple,compact,integrated unit design) Small scale production Process scale studies Integrated design with certain options  Smaller footprint & more compact  Priced 10-15%lower than competition  Better features AKTA Pilot is positioned more as a Small scale production Process scale up studies  AKTA “mix and match" multiple components  Complex decision making  Integrated system with few options  Akta priced 15% above Qsep 1000

Sepragen Corporation Advantages QuantaSep 1000 vs Akta Pilot FeaturesQsep 100Akta PilotBenefits Hardware Buffers128Greater versatility- enables all 3 columns to be used without stopping run Fractions108More capability for collecting fractions from multi- column run Low System Backpressure YesNoOperational over 100% range vs. only 60% for Akta Auto Air Eject System YesNoColumn protected from air intrusion Leak detectionYesNoProtection from loss of material Flow rate/ pump ml/min ml/minGreater dynamic range…..can process large dilute batches faster No Bubble trapYesNoBetter chromatography less dilution Software Point & Click software YesNoSoftware easy to learn, use and troubleshoot; Akta Software unwieldy to program, train and run overkill for production Real time Analysis YesNoBetter process control; lower losses Real time overlays YesNoIncrease run- run consistency; lower losses and increase yields 42

Sepragen Corporation Advantages of QuantaSep Software vs Competition Software Features SepragenAmershamPallMilliporeBenefits Software Point and Click Manual Operation YesNo Less training time Online Data Analysis YesNo Lower failure rate Ease of Operation Ease of Use Ease of Programming Ease of Use Real Time Overlays YesNo Improved reliability Integrate Chrom and UF/ DF YesNo 2 operations for the price of one 43

Sepragen Corporation QuantaSep Skids vs Competition SepragenGEPallMillipore HardwareQsep Qsep 5000 Akta ProcessPK SeriesKPrime Series Benefits Product Range6333Greater range Turndown Ratio of Pumps 100:110:130:110:1Greater dynamic range Typical Flow Range50ml/min- 5000ml/min 600ml/min- 6000ml/min 100 ml/min ml/min 150ml/min- 1500ml/min Greater dynamic range Gradient (at 50% FS)5-95%10-90% 20-80%Better Chromatography Online Buffer DilutionYes NoSave labor, space, time System Volume750ml~2000 ml2000 ml Better chromatography Footprint22”x27”x46”30”x60”x72”30’x60’x72”30”x60”x50”Increased Capacity Air EjectionElectronicBubble trap Increased Reliability Leak DetectionYesNo Increased Reliability Leak SensorYesNo Increase reliability Easy to use softwareYesNo Easy training; usage and intervention 44

Sepragen Corporation QuantaSep vs Competition SepragenAmershamMillipore FeaturesQsep Qsep mm Bioprocess K Prime 40+Benefits Inlet Valves6+6, Greater flexibility Columns3,111Greater flexibility Fractions10,644Greater flexibility Dual wavelength UVYes Greater flexibility 45

Sepragen Corporation Customer Quotes Human Genome Sciences, Inc. "We have purchased several QuantaSep Systems and use them routinely in development and manufacturing. They have provided us with the capability to scale-up quickly and reliably. The robust design and compact size has enabled us to add productive capacity without waiting for additional construction. The QuantaSep software is easy to learn and use. Automated processing and report generation have enabled us to get more done with the same resources. Our quality and consistency have improved, as well. I would highly recommend the QuantaSep® family of products to anyone." Mark Oelkuct, Purification Manager Cohesion Technologies "At Cohesion we have used a QuantaSep 1000 as a workhorse in both manufacturing and process development. We are quite satisfied with its performance. In our hands the QuantaSep has been a reliable instrument that is also easy to use and maintain. The flow rate range of the 1000 matched out commercial requirement for one process and pilot scale for another. It fits well into smaller processing spaces (critical when working in Palo Alto). Again, we have been happy with our QuantaSep 1000 and would be willing to discuss our experience with others" Lou Sehl, Ph. D., Senior Scientist and Team Leader 46

Sepragen Corporation Customer Quotes Dade Behring "The efficiency of these products, in our hands, provides a significant advantage over other purification equipment we have evaluated for the following reasons: 1) The QuantaSep software is easy to use and train. 2) The QuantaSep allows us to reduce our standard direct hours, thus reduce our projected costs, by allowing a production chemist to perform multiple purification tasks simultaneously. This system eliminates the need to "baby-sit" all the individual purification steps. With reduced labor costs, the return on investment is easily less than two years for the QuantaSeps. 3) This programmable system insures lot-to-lot consistency, resulting in consistent elution profiles vs. the built in variability with more manual operations. A critical advantage for a GMP production process. 4) And finally, one unique advantage of this system is its versatility. We can run both our small and large volume production (5 liter to 200 liter) runs with the change over feature. No other systems we have investigated have that volume flexibility." Dennis Gould, Manager, Antibody Manufacturing 47

Sepragen Corporation Representative Quantasep Users for Quantaseps 48 Domestic Customer ProductInternational Country CompanyProduct Siemen’s Diagnostic, Dyax Qsep 1000 LXJapanAsahi KaseiQsep 1000 NeovatechQsep 1000sGermanyBaxterQsep 1000 Dow PharmaQsep 1800/ 1000SwitzerlandLonzaQsep 1000 Lonza, Biogen- Idec Qsep 1000, 1800 Qsep 1000 IndiaCadilla PharmaQsep 1000 Amgen, Roche Diagnostics Qsep 100BelgiumHenogenQsep 1000 HGSQsep 1000/ 1800U.K., BelgiumGSKQsep 1000, Qsep 40Lpm Schering Plough Qsep 1000s, 5000China, RussiaseveralQsep 100/ 1000

Sepragen Corporation Summary 49  Reduce Project backlog  Improve product backlog  Improve product quality and reliability  Reduce Project backlog  Unattended clinical Production 24/7 NOW!  GMP documentation automatically  Easy scale-up 500X  Improved process economic by 50%

QuantaSep ® Additional Slides

Sepragen Corporation Custom Explosion Proof Chromatography Skids Liter per minute Class 1, Div 1 or 2 Stainless Steel construction Fully drainable Multi-wavelength detection Diaphragm pumps 51

Sepragen Corporation 52 Quantasep 100 Quantasep 1000 Flowrate 1 – 100 mL/min10 – 1000 mL/ min Tubing ID (mm) 1.59 (1/16”) 6.35 (1/4”) Connections ¼.28 thread½” tri-clamp Hold-up volume 7 mL120 mL Dimensions (WxDxH ) 660 x 533 x 381(mm) (26"X 21" X15") 660 x 533 x 381(mm) (26"X 21" X15") Un-crated weight (kg) 57 (125 lbs)66 (145 lbs) Quantasep General Specifications

Sepragen Corporation 53 Sensor Range Conductivity ms± 2% pH 1-14 pH± 0.3 UV (280nm) 0-2 Au± 2% UV (260nm) option 0-2 A-u± 2% Active Air Trap >5mm (0.20")0.6 x tubing ID Operating Pressure 0-7 bar (0-100 psi) ± 0.07bar (± 1 psi) Leak 5 mL - Flow:Qsep100 Qsep1000 Qsep mL/min mL/min ml/min ± 3% Operating Temperature o C - Accuracy Sensor Specifications

Sepragen Corporation 54 Quantasep Flow cell

Sepragen Corporation 55 Quantasep 100- Inside Look

Sepragen Corporation 56 Quantasep Inside Look

Sepragen Corporation 57 Flow cell and column & fraction manifolds forQuantasep 1000

Sepragen Corporation 58 pH Ref pH Probe UV Lamp Flow Cell Multimode Detector Compact and Zero lag time detector helps minimize footprint