PendoTECH TFF Process Control & Data Acquisition System

PendoTECH TFF Process Control & Data Acquisition System Product Information Ideal for many applications in biopharmaceutical processing: Ultra-Filtration / diafiltration (UF/DF) of proteins and viruses Cell culture harvest and perfusion processes Virus removal processes Adds automation, in-line process monitoring and data collection to your processes Complete batch control with 6 built-in programable recipes System interaction via a PC-based Graphical User Interface Real time trending and all data is written for permanent record Features use of PendoTECH Pressure Sensors that are available from a luer size to 1 inch inner diameter No limitation on process scale- from milliliters and up with any filter Integrates with different types of pumps and different brands of scales Built in conductivity & ph measurement Options for filtrate flow/flux measurement in addition to ability to measure other process parameters via configurable inputs Several advanced features afford additional system utility IQ/OQ templates available for cgmp manufacturing Benchtop System Process Development Pilot/Clinical System Copyright 2012 PendoTECH TFFS-3

Product Overview Completely and efficiently automates your TFF/Crossflow Filtration Process Recipe based control of entire concentration and diafiltration process with multiple options for automated diafiltration end point (filtrate weight, conductivity, ph, air in buffer feed line, total flow) Pressure measurement in psi or bar and calculation of trans-membrane pressure (TMP) and delta-p with PendoTECH Pressure Sensors that are available from a luer size to 1 inch inner diameter Interact with the system via an easy to use graphical user interface (GUI) that includes a trending module with many advanced features Alarms for all process parameters that shut-down the pumps Alarm features include a delayed detection on the minimum inlet pressure that can stop the system if the inlet pressure drops due to a flow path problem Automation and alarm features allow the system to be operated with minimal user interaction Completely sealed front panel for use in clean environments where frequent wipe-down is required. Process control via integration of industry standard scales and pumps Can be used at any process scale ph probe input via a BNC connector that can accommodate standard ph probes and the GUI includes an easy to use probe calibration wizard Conductivity probe/flow cell input to embedded conductivity transmitter with temperature display and compensation Air detector end-point can be used for Fed-batch process where product is fed to the main vessel and dynamically concentrated via diafiltration mode Filtrate flow meter input for optional disposable rotary flow meter, ultrasonic flow meter, or other that includes the ability to totalize flow Two inputs available for other sensors with 4-20 milliamp outputs to enable collection of additional process data that can be configured for advanced features and alarms points such as UV, temperature or filtrate line One input can be used to input external conductivity signal The system may be controlled remotely via a PC, ipad or smart phone by using 3rd party software. Process details are visualized on the graphical interface and the system interaction is via the PC so remote control is possible by simply accessing the PC. The pre-alarm notification points can be used to send email alerts. Retentate flow may be controlled by either installation of a retentate flow meter or by deltap. System has TMP output signal that can be connected to external non-invasive control valve to control system TMP. CE tested for EMC and LVD Graphical User Interface - Simplifies Control System Interaction The GUI is designed for use with a mouse or touch-screen operation. Clicking a numeric field is followed by appearance of a pop-up key pad for data entry. Values entered that are out of range are rejected with a message. There are four tabs for easy navigation: 1. Setup View- used to enter experiment information, program recipe, set alarms and to create a data file where all process data will be stored 2. System View- used to view current process values and change pump flow rates 3. Trends View- utility to trend process variables that is loaded with features to dynamically view the data of interest, ability to quickly auto-scale or manually scale the axes, and ability to export a trend of interest either as data or a graphics file 4. Maintenance View- used to set up pumps based on tubing size, calibrate ph and conductivity via easy to use wizards, select units of measure, configure flow meter and more. 4 Tabs for Fast and Easy Navigation (system view shown) Critical Alarm - Critical alarm that stops pumps appears here in RED. Notes - Click here and a pop-up box appears where an electronic note can be entered. The note is written to the data file one time and time-stamped. Notifications - Give notifications but do not trigger an alarm. These can be enabled to send email alerts also. The system view can be customized with selection of a hollow fiber or cassette module graphic and with the ability to enable/ disable the filtrate pump. 2

Process Overview TFF/Cross Filtration Process Overview A tangential flow filtration (TFF) or cross flow filtration process using a hollow fiber filter module (versus a plate & frame cassette flat sheet device) is represented in Figure 1. Liquid is fed from a product vessel (or bioreactor) by a circulation pump to a filter module containing numerous hollow fibers and the liquid flows into the inner cross section of the individual fibers. The wall of the hollow fiber is the filter membrane. As is shown in Figure 2, a certain amount of liquid and liquid components smaller than the pore size of the fiber wall permeates through the wall (the filtrate). The filtrate collects in the module shell and the shell has ports for removal of filtrate from the shell (the void area between the fibers is closed at both ends to prevent the liquid that is entering the filter module from going directly into the shell). The feed pressure (P IN ) is higher than the retentate pressure in (P OUT ) because of the pressure drop as liquid flows through the narrow fibers and returns to the vessel. There is also a pressure drop across the fiber wall and the filtrate pressure is measured at P F. Monitoring of these pressures is critical to measure process performance and for process control. The cross flow rate is orders of magnitude above the filtrate flow rate and it is this phenomena that prevents a membrane filter from clogging from material that would rapidly clog a membrane filter operating in normal flow filtration. In flat sheet devices, even though the geometry of the device is different, the operation of the process is similar. TFF is a very effective process selection in many areas of biopharmaceutical processing. Depending on the process, a filtrate pump may be used to limit the filtrate flow and prevent rapid filter fouling. A throttling valve may be used on the retentate tube to create back pressure to drive liquid through the membrane. In a TFF process, as filtrate is removed, the vessel contents are concentrated. In a diafiltration process, liquid is added to the product vessel as the same rate of filtrate removal. Process Schematic with Available Inputs and Outputs Product Container Buffer Container Cross Pressure Control Valve Main Vessel Cross Meter DPV1 DPV2 Buffer Feed Pump Circulation Pump ph sensor Conductivity sensor Pressure sensor Scale Scale Solenoid Graphical User Interface Data TFF Control System Copyright 2012 PendoTECH TFFS-3 3

User Interface Details System View current process values and change pump flow rates External sensor readings Recipe Info All process variables are displayed including calculated values such as TMP and DeltaP Gauge ranges set by min/max alarm set points only appears if flow meter configured Pumps rotate while running Estimated flow rate can be calculated by an algorithm based on the change in filtrate scale rate. Indicators in blue can be changed while running by clicking on the indicator Setup Enter experiment information, program recipe, set alarms and creates a data file where all process data will be stored 6 Diafiltration endpoint options listed Information is written to header of data file when data collection is started; then it becomes uneditable 6 options available When Start Process Data Collection is selected, a dialog box appears so a file name and location can be entered. All process data is saved to a CSV file that can be opened later in software such as Excel. Settings for selected recipe are entered here Feed pump only programmed for Diafiltration steps Ability to save/recall frequently used recipes Alarms set-points Will stop pumps Filtrate pump appears here only if enabled Notification points (create no action) Configure notification email alerts 4

Utility to trend process variables with features to view the data of interest, auto or manual scale the axes, & export a trend as a data or graphics file Trends Slide to change cursor value Options to select Auto-scale or Manual scale on all axes Powerful tools to zoom, export an image of the current trend and much more Quickly compare current values to cursor value Ability to change plot update rate Export the current trend only to open in software such as Excel Maintenance Use to set up pumps based on tubing size, calibrate ph & conductivity via wizards, select units of measure, configure flow meter & more Functions Include: Zero pressure sensors Enable/disable filtrate pump Select conductivity range Calibrate ph Set units of measure Set-up pumps Select graphic display for filter Configure the flow meter Zero flow meter total Set range of external signals Enable/disable Diafiltration Valves Exit program ph wizard zoom Filtrate Meter that is also used to determine flux, has a choice of flow meters that set the K-factor for the flow meter or the K-factor may be entered manually or determined by a user calibration wizard. Copyright 2012 PendoTECH TFFS-3 5

Integration Options Control System Back Panel Input/Output Connections PendoTECH Pressure Sensors Pressure sensor cables provided with the system accept the PendoTECH Single Use Pressure Sensors (below). Even though these are called single use, they are robust enough to be re-used for process development work where cross-contamination is not a concern. Sizes available luer, 1/4, 1/2, 3/8, 1/2, 3/4 and 1 hosebarb. Ultra secure tubing retainers are available or higher pressure operations. The system comes with the required cables to enable the sytem to be quickly up and running. All connections are keyed to prevent connection of a cable to the wrong connector. Pumps and scales may be delivered with the system or existing equipment or self-procured equipment may be used. Throttle Valve Option Accessory Throttling Tubing Pinch Valve that can control TMP independent of the control system Scale Options Most scales with RS232 communication can be used Control system has customized software interface for optimal integration of scales to enhance performance A scale selection menu on the process control system is used to quickly configure the RS232 parameters for the different scale brands. Pump Options Any pump with a remote speed control input can be used- no process scale limitations! Peristaltic, rotary lobe, diaphragm pump, and other Pump Setup function used to quickly enter the pump parameters Masterflex pump selection guide available from PendoTECH The pump cables are supplied to interface to the remote control connector on the user selected pumps as shown in the example below. Interface Connector Pump Cable (Masterflex Pump Cable Shown) Example of Pump Back Panel with remote interface connector meter Options Different options are available for Filtrate /Flux measurement such as the low-flow ultrasonic (<100m/min) and rotaty flow meters for higher flow rates. For retentate flow where there may be a shift in viscosity and/or conductivity, flow must be measured by other types of flow meters such as the PendoTECH Coriolis Meter. Following is a selection of just some of the pumps that can be integrated to the system Rotary Meter PendoTECH Coriolis Low Ultrasonic 6

Air Detector Option The non-invasive ultrasonic air detector detects air in a tube placed into the detector. There is an integral LED that indicates liquid presence. The tube can be opaque because the sensing mechanism is sound waves. The software has a user entered detection delay to prevent false endpoints. Built-in Conductivity & Temperature Monitor Built-in conductivity monitor also measures temperature and performs temperature compensation. Temperature is measured by a 100 Ohm Pt RTD. There is a simple one-step calibration procedure and probes with constants of K=1 or K=10 may be used. The range is selectable from either 0-19.99 ms or 0-199.9 ms. The PendoTECH in-line sensor, stainless steel or epoxy dip-type probes and a glass flow cell is available. Buffer Feed & Retentate tubes can be positioned to deliver liquid to the bottom PendoTECH 2 Liter Vessel Removable collars for tube adjustment/ removal Spare hole for vent filter Conductivity Probe Options: Top and base attached by 4 inch sanitary clamps 2L Vessel made of polysulfone - easily removed for cleaning Conical base with low point drain Stand with adjustable legs for different stir plates Stir bar locator in the center of the base Complete Small Scale Benchtop Setup Diafiltration Feed Selection Pinch Valves Air Detector For Fed Batch End Point Retentate Meter Throttling Pinch Valve Circulation Pump Low Filtrate Meter PC for Graphical User Interface Diafiltration feed pump Vessel with stirrer Cond. Cell Scales Pressure Sensors Control System Throttle Valve Controller Copyright 2012 PendoTECH TFFS-3 7

Integrated Cart Systems Process Development Cart Diafiltration Feed Selection Pinch Valves Diafiltration Feed Pump Air Detector For Fed Batch End Point Throttling Pinch Valve Cond. Cell 2 Liter Vessel with Stirrer Conical Bottom With Low Point Drain Retentate Meter Pressure Sensors PC for Graphical User Interface with Touch-Screen Filtrate Meter Scale Throttle Valve Controller Circulation Pump Waterproof integral keyboard/ mouse on slideout tray Control System Heavy Duty Locking Casters Filtrate Scale (Deluxe Cart also available) Pilot/Clinical System Throttle Valve Controller Water Resistant PC for Graphical User Interface with Touch-Screen and Wireless Networking Control System Retentate Meter (optional-not shown) Throttling Pinch Valve Pressure Sensors Surface for Filter Filtrate Meter 30 Liter Vessel with Stirrer with Bottom Drain Conductivity Cell Diafiltration Feed Selection Pinch Valves Diafiltration Feed Pump Heavy Duty Locking Casters for Moving Air Detector For Fed Batch End Point Scales Circulation Pump Pinch Valves For Automated Recovery 8

Advanced Features Remote Access Easy ability to operate system remotely from another PC using software such as Real VNC, Remote Desktop, Timbuktu, GoToMyPC, LogMeIn and others or smart devices such as the iphone/ipad Circulation Pump Control Options for Retentate Control which adjusts the flow rate of the circulation pump: A Retentate flow set point can be controlled by enabling this feature and installing a retentate flow meter such as the PendoTECH Coriolis Meter DeltaP can be controlled by the GUI software Adjust algorithm by entering the DeltaP setpoint These modes are activated on the Maintenance Tab. Additional control settings are added to the other tabs to optimize this feature. This mode allows the pump to be slowed to drop the filter inlet pressure to prevent a high pressure alarm during a concentration step where the fluid viscosity increases. This mode works in conjuction with and independent of automated TMP control. Email Notification The pre-alarm notification points can be used to send email alerts. The system is given a name and the email addresses to send the alerts are entered. There is a built-in mail program to send these notifications with a default mailbox which may be replaced by a user configured mailbox. pendotechpsc j.jones@abc.com External Input The two external inputs can be used to collect data from a wide variety of sensors not built into the system. The input signals are configured in the software and alarm points on these values may be entered also. These inputs give the ability to instantly integrate the PendoTECH Temperature Sensors and UV Sensors. UV Sensor with Transmitter Temperature Sensor with Transmitter Copyright 2012 PendoTECH TFFS-3 9

Specifications Detail Specifications Dimensions (HxWxD) 6.125 x 16 x 11.5 (15.5575cm x 40.64cm x 29.21cm) Weight 8 lbs (3.6 kg) Enclosure Material Power Requirements Pressure Sensor Inputs Pump Control AIr Detector Input Meter Input External Inputs ph Input Conductivity Input Scale Inputs PC Requirements 304 Stainless Steel 100-240 Volts, 50-60 Hertz, 2 amp max PendoTECH Single Use Pressure Sensors (-7 to 75 psi / 0.5 to 5.2 Bar) Speed Control: 4-20mA; Start/Stop: Relay 3-48VDC, up to 3A continuous Digital input with 24VDC supply 5V Digital pulse input with 5VDC or 24VDC supply Analog Signal - both 4-20mA Standard probe input via BNC connector 4 wire input (2 wires for 100 ohm Pt RTD) K=1 or K=10 with range selectable for either 0-19.99mS or 0-199.9mS RS232 Communication Windows XP or Vista, 2 GHz or faster, 2GB of RAM Ordering Information System PDKT-PCS-TFF TFF Process Control System with Graphical User Interface Software and interface cables PUMPS (Others Available) PUMP-MF-LS-TW PUMP-MF-LS-TKW PUMP-MF-LS-HP PUMP-WM-620 PUMP-Q150SU PUMP-Q150SS PUMP-Q1200SU PUMP-Q1200SS PUMP-Q1200HSU PUMP-Q1200HSS Masterflex General Purpose Digital, with RPM display only, 600RPM with EasyLoad II pump head for thin wall L/S tubings Masterflex General Purpose Digital, with RPM display only, 600RPM with EasyLoad II pump head for thick wall L/S tubings Masterflex General Purpose Digital, with RPM display only, 600 RPM with High Performance pump head for thick wall L/S tubings Watson Marlow Model 620U/R 265 RPM Pump with to 12.7 l/min Quattro Pump Q150 Single Use chamber (up to 3L/min) and includes 3 chambers Quattro Pump Q150 Stainless steel chamber (up to 3L/min) Quattro Pump Q1200 3 Pump Single Use chamber (up to 11L/min) and includes 3 chambers Quattro Pump Q1200 3 Pump Stainless steel chamber (up to 11L/min) Quattro Pump Q1200 5 Pump Single Use chamber (up to 18.3 L/min) and includes 3 chambers Quattro Pump Q1200 5 Pump Stainless steel chamber (up to 18.3L/min) filtrate flow meter FM-22WV FM-22WV-E FM-23WV FM-23WV-E FM-US-LF PCFM-31 PCFM-32 PCFM-42 PCFM-82 Rotor for Disposable PVDF Turbine meter 1/4 inch, 0.1-1.0 LPM, clip mount. With individual calibrations. Electronic Assembly for one PVDF rotor with 1/4 inch hose barb (includes one rotor), 0.1-1.0 LPM clip mount. With individual calibrations. Single Use Rotary Meter, non-sterile, PVDF, 1/2 inch hose barb, 0.3-20.0 LPM, clip mount. With individual calibrations. Electronic Assembly for one PVDF rotor with 1/2 inch hose barb (includes one rotor), 0.3-20.0 LPM, clip mount. With individual calibrations. Low flow ultrasonic flow meter (with 1/16 inch ID, 1-100 ml/min) PendoTECH Coriolis Mass meter with 0.25 /6.35 mm ID (range 5-1,500 grams/min) PendoTECH Coriolis Mass meter with 0.25 /6.35 mm ID (range 5-4,000 grams/min) PendoTECH Coriolis Mass meter with 0.25 /6.35 mm ID (range 60-5,000 grams/min) PendoTECH Coriolis Mass meter with 0.25 /6.35 mm ID (range 750-24,000 grams/min) Copyright 2012 PendoTECH TFFS-3 10

Ordering Information CONDUCTIVITY COND1-TFF COND2-TFF COND3-TFF COND4-TFF Conductivity Probe K=1 with 100ohm Pt RTD for temperature measurement for TFF Process Control System, stainless steel with flow cell Conductivity Probe K=1 with 100ohm Pt RTD for temperature measurement for TFF Process Control System, epoxy Conductivity Glass flow cell K=1 for 1/4 ID tubing w/100ohm Pt RTD for temperature measurement for TFF Process Control System Conductivity Probe K=1 with 100ohm Pt RTD for temperature measurement for TFF Process Control System, stainless steel with sanitary flange AIR DETECTOR Part Number AD-16 AD-17 AD-24 AD-36 AD-73 AD-88 AD-100 Tubing OD 1/4 3/8 7/16 9/16 5/8 7/8 1 DIAFILTRATION VALVE PDKT-PVE2-TFF-S PDKT-PVE2-TFF-M TFF Control System Electric Diafiltration Pinch Valve Pair - Small for 1/8 inch ID TFF Control System Electric Diafiltration Pinch Valve Pair - Medium for 1/4 inch ID ph* PH-GFC PH-GFCP PH-GFCC ph probe glass flow cell with 1/4 inch barb ph probe for glass flow cell ph probe & glass flow cell with 1/4 inch barb * Any ph probe will work with system. Other options available from PendoTECH 2 Liter Vessel PDKT-TNK Complete 2L tank setup with stir plate, 2 dip tubes, and stand 2LPS Polysulphone cylinder with 4 inch TC ends for 2L vessel with 2 EPDM gaskets TNK-BASEPS Polysulphone vessel base with 4inch TC eonnection, stirrer bar locator, and low-point drain TNK-2LSTAND 2L Delrin vessel stand with 4 adjustable stainless steel legs TNK-TOPPS Polysulphone vessel top with 4inch TC eonnection, and 3 holes with for 5/16 inch OD dip tube TNK-DIPCLMP One Delrin split clamps to hold vessel dip tubes to 2L vessel lid TNK-2L-STRBAR Stir bar for 2L poly sulphone vessel TNK-2L-HBSS 1/4 inch hose barb vessel outlet for 2L vessel base- 316 Stainless steel TNK-DIPTUBE 5/16 inch OD dip tube with 1/4 inch ID, 15 inch length TNK-TCCLMP One 4 inch light duty TC clamp TNK-2L-STRPLATE Stirrer plate for 2 liter vessel Warranty Seller warrants that the Software will execute the programming instructions provided by Seller, and that the Goods manufactured by Seller will be free from defects in materials or workmanship under normal use and service until the expiration of (24) months from the date of shipment by Seller. Expendable items are warranted to be free from defects in material and workmanship under normal use and service for a period of ninety (90) days from the date of shipment by Seller. Products purchased by Seller from a third party for resale to Buyer ( Resale Products ) shall carry only the warranty extended by the original manufacturer. Buyer agrees that Seller has no liability for Resale Products beyond making a reasonable commercial effort to arrange for procurement and shipping of the Resale Products. If, within thirty (30) days after Buyer s discovery of any warranty defects during the applicable warranty period, Buyer notifies Seller thereof in writing, Seller shall, at its option and as Buyer s sole and exclusive remedy hereunder, promptly correct any errors that are found by Seller to exist in the Software, or repair or replace F.O.B. point of manufacture, that portion of the Goods or Software found by Seller to be defective. All replacements or repairs necessitated by inadequate preventive maintenance, or by normal wear and usage, or by fault of Buyer, or by unsuitable power sources or by attack or deterioration under unsuitable environmental conditions, or by abuse, accident, alteration, misuse, improper installation, modification, repair, storage or handling, or any other cause not the fault of Seller are not covered by this limited warranty, and shall be at Buyer s expense. Seller shall not be obligated to pay any costs or charges incurred by Buyer or any other party except as may be agreed upon in writing in advance by an authorized Seller representative. All costs of dismantling, reinstallation and freight and the time and expenses of Seller s personnel for site travel and diagnosis under this warranty clause shall be borne by Buyer unless accepted in writing by Seller. Failure by Buyer to give such written notice of defects within the applicable time period shall be deemed an absolute and unconditional waiver of Buyer s claim for such defects. Goods repaired and parts replaced during the warranty period shall be in warranty for the remainder of the original warranty period or ninety (90) days, whichever is longer. This limited warranty is the only warranty made by Seller and can be amended only in a writing signed by an authorized representative of Seller. Except as otherwise expressly provided in the Agreement, there are no representations or warranties of any kind, express or implied, as to merchantability, fitness for particular purpose, or any other matter with respect to any of the goods or software. Copyright 2012 PendoTECH TFFS-3 11