Instruction Manual MediPrep 120

Instruction Manual MediPrep 120 ERWEKA GmbH * Ottostr. 20 22 * 63150 Heusenstamm * Germany * Tel: +49 (0) 6104 6903-0 Fax: +49 (0) 6104 6903-40 * E-mail: info@erweka.com * www.erweka.com Directors: Werner G. Müller, Claudia Müller, Manfred Koller * District court Offenbach HRB 2382

Document version MediPrep 120 Version Table Date Document Change Version* 04.06.2013 1.0 08.03.2016 1.1 new number (old No.: 475-309-0001), layout (CE) * In the X.Y document version X means a technical change and Y a document change only. Date: 2016-03-08 Firmware version: from 2.0 Document No.: 475-309-0001 Document version: V1.1 Language: English ERWEKA GmbH * Ottostr. 20 22 * 63150 Heusenstamm * Germany * Tel: +49 (0) 6104 6903-0 Fax: +49 (0) 6104 6903-40 * E-mail: info@erweka.com * www.erweka.com Directors: Werner G. Müller, Claudia Müller, Manfred Koller * District court Offenbach HRB 2382

Instruction Manual Table of Contents 1 INTRODUCTION... 6 1.1 SYMBOLS USED IN THE MANUAL... 6 2 TECHNICAL DETAILS... 7 2.1 INTRODUCING MEDIPREP 120... 7 2.2 OVERVIEW DIAGRAMS AND TERMINOLOGY... 8 2.3 TECHNICAL DETAILS... 10 2.4 LIST OF COMPONENTS... 11 2.5 UNPACKING AND CHECKING... 12 3 INSTRUMENT INSTALLATION... 13 3.1 ASSEMBLING... 13 3.2 FUSES... 13 3.3 MICRO SWITCH... 14 3.4 SAFETY INSTRUCTIONS... 14 3.5 STARTUP SCREEN... 14 3.6 KEYPAD... 14 4 MAIN MENU... 16 5 CONFIGURATION... 17 5.1 LANGUAGE... 17 5.2 TIME... 17 5.3 DATE... 17 5.4 HARD DEGAS TIME... 18 5.5 PRINTOUT... 18 5.6 DISPENSE... 18 6 ADJUSTMENT... 19 6.1 SETTING THE DISPENSE TEMPERATURE... 19 6.2 LOAD CELL OFFSET (IF NECESSARY)... 20 6.3 FIRST LOAD OFFSET (IF NECESSARY)... 21 7 TEST... 22 7.1 NUMBER OF VESSELS... 22 7.2 VOLUME REQUIRED... 22 7.3 HEATER... 23 7.4 STARTING AND PERFORMING A RUN... 23 7.5 PREHEATING... 23 7.6 CHAMBER FILLING / DEGASSING AND DISPENSING... 23 8 CALIBRATION... 24 8.1 CALIBRATING THE LOAD CELL (TWO-POINT CALIBRATION)... 24 8.2 PERFORMING OQ (DISPENSE VOLUME)... 25 8.3 PERFORMING PQ (DISSOLVED OXYGEN)... 26 8.4 CALIBRATION DATES... 26 9 SYSTEM FLUSH... 27 10 MAINTENANCE AND CLEANING... 28 10.1 SERVICING... 28 10.2 TECHNICAL SUPPORT... 28 10.3 DAILY CLEANING TASKS... 28 10.4 MONTHLY CLEANING ROUTINE... 28 10.5 CLEANING DOWN FOR STORAGE PERIODS... 29 Page 4 of 35

Instruction Manual 11 TROUBLESHOOTING... 30 11.1 ERROR MESSAGES... 30 11.2 MOVING THE INSTRUMENT... 32 11.3 OPENING THE INSTRUMENT... 32 APPENDIX... 33 TEST REPORT... 33 LOAD CELL CALIBRATION REPORT... 33 OQ VALIDATION REPORT... 33 PQ VALIDATION REPORT... 33 WARRANTY... 34 COPYRIGHT... 35 Page 5 of 35

Introduction 1 Introduction Thank you for purchasing the ERWEKA MediPrep 120 1-Liter Degasser! To assure continuous and accurate function of the instrument, read this manual thoroughly before operating the instrument and keep it for further reference. If you have any questions about the operation of this instrument or would like to know any additional information, please do not hesitate to contact ERWEKA. Our products are under continuous development and improvement. Therefore, we reserve the right to make changes without notice. When ordering the spare parts or in the event of the instrument requiring repair, supply the following information: type of the instrument (as it is specified on the identification label at the instrument s rear panel) serial number of the instrument (as it is specified on the identification label at the instrument s rear panel) short description of the fault The instrument is shipped with the load cell locked by the load cell locking key. Read chapter 3 Instrument Installation carefully before operating the instrument. This instrument is not designed for use with surfactants! 1.1 Symbols used in the manual Information: this note provides you with additional information specifically useful at this point of work with the instrument. Caution: this note draws your attention to ensure smooth operation of the instrument. Warning: this note contains tips which should be taken into consideration to prevent damage or malfunction of the equipment. Page 6 of 35

2 Technical Details Technical Details 2.1 Introducing MediPrep 120 The MediPrep 120 has been designed to prepare the media for dissolution tests by removing dissolved oxygen to less than 5.5 ppm and preheating the media for your convenience up to the best temperature for your laboratory conditions prior to accurate temperature setting in the dissolution tester. The instrument is designed to be used with vessels for any make of dissolution bath. The vessels are simply placed inside the vessel holder and the medium is dispensed directly into the vessel. Volumes from 250 ml to 1000ml can be selected in 10 ml steps. The instrument has easy-to-use menus designed to guide you through every process from performing a test to calibrating and flushing. A simple keypad has been used along with the clear white-on-blue display. Heating is performed by flow-through heater which can preheat the medium (ready for accurate dissolution stabilization in the dissolution bath) from ambient up to 50 degrees with accuracy of approximately ±2 C for the required volume. This saves considerable warm-up time when preparing your dissolution tester. The shipped instrument is set up to quickly heat the media to approximately 37 C at vessel volumes between 900 and 1000ml 1. The heater can be simply adjusted for vessel volumes below 900 ml. The dispense temperature is adjustable. The heater can also be switched off for tests that do not require heated media. The medium is dispensed by weight using the internal load cell. With the MediPrep 120 you do not need to wait for large quantities of media to heat up. In busy labs where different media are often used, the MediPrep 120 is an ideal dissolution media preparation tool allowing you to switch media types with a single flush routine. Do not use any alcohol or organic media when operating the MediPrep 120! 1 The instrument may require some temperature adjustment during installation as laboratory conditions will vary from those at the manufacturer. Page 7 of 35

2.2 Overview diagrams and terminology Technical Details 2.2.1 Front view 1. Micro switch 2. Heating indicator 3. Keypad 4. Base unit of MediPrep 120 5. Load cell cavity/plastic insert 6. Thermal printer with paper roll (sticky back) 7. Display 8. Dispense nozzle 9. Vessel holder (with rubber plate) 10. Water collection tray with lid Page 8 of 35

Technical Details 2.2.2 Rear view 1. Mains switch 2. Power inlet 3. Fuses 4. Empty switch 5. Glass filter 6. Waste outlet 7. Media inlet Page 9 of 35

2.2.3 3-vessel rack (optional) Technical Details 2.2.4 Calibration kit 1. Calibration plate (with shaft and screw) 2. Power cord 3. Foam case 4. Media inlet tube 5. Load cell locking key and plastic insert 6. Inline filter (connected to media inlet tube) 7. Test weight 500 g 8. Test weight 1000 g 2.3 Technical details Dimensions: Height: [mm] 625 Width: [mm] 232 Depth: [mm] 575 Weight: [kg] gross packed 48 Weight: [kg] net 25 (plus case 3.5 kg) Power supply: 230VAC/50Hz/60Hz 115VAC/60Hz Additional voltages available upon request IP rating (acc. EN60529) IP32 Fuses: Safety fuse: 230v/50Hz 2 x 10A 1 x 2A 115v/60Hz 2 x 16A, 1 x 2A (option) Temperature: Temperature control: Internal PT100 sensor (acc. to Din Kl. B) Heater: Internal flow-through heater Page 10 of 35

Technical Details Heating rates: 1950W at 230VAC/50Hz 2000W at 115VAC/60Hz (option) Temperature range: Single set temperature from ambient to 50 C Function: Power consumption: 2200W, 9.5A, @ 230V single phase Vessel heating and dispense cycle at 1000 ml Control: Degassing type: Approx. 1min. 30 sec. (+ hard degas time if required) 6 vessels = approx. 9 min. 8 vessels = approx. 12 min. ERWEKA custom keypad Vacuum 200 mbar based on 1000 mbar atmospheric pressure < 5.5 ppm Dissolved oxygen level while dispensing: Dispensing principle: Pumping Hard degas time: 0-60 sec. (can be increased as required) Dispensed volumes: Min.: 250 ml Max.: 1000 ml Step: 10 ml Accuracy: ±1% Media types: All internal parts are inert. Therefore, most dissolution media can be used including aggressive HCl solutions. The instrument should be properly flushed at the end of each day. (Contact ERWEKA if in doubt.) Surfactants: The MediPrep 120 is not designed to be used with surfactants Printer: Built-in thermal printer Required installation environment: Ambient temperature in operation +10 C up to +30 C Storage and transport temperature -10 C up to +55 C Relative humidity 25-80% / no condensation 2.4 List of components The ERWEKA MediPrep 120 is delivered with the following components: Quantity Description Part Number 1 Base unit of MediPrep 120 220V version Including rear filter, complete printer with printer roll (thermal, 600600 sticky back) 115V version 600700 1 Water collection tray with lid 600012 1 Media inlet tube 090270 1 Inline filter (connected to media inlet tube) 091512 1 3-vessel rack (optional) 303163 1 Power cord 010257 1 Instruction manual S1 Page 11 of 35

Technical Details 1 Load cell locking key 600019 1 Plastic insert for load cell cavity 040802 1 Test weight 1000 g 092011 1 Test weight 500 g 092010 1 Calibration plate (with shaft and screw) 600001 1 Calibration case 090728 1 Media tank tube (530 mm length, 12 mm diameter polypropylene) 090271 The following spare parts are also available: Quantity Description Part Number 1 Glass filter 080325 1 Printer paper roll (sticky back) 092012 1 Printer paper roll (non-sticky back) 092013 1 Replacement printer 091711 1 Heater cartridge 220V 011631 1 Heater cartridge 115V 011623 1 Load cell 039911 1 Micro switch (vessel in position) 011105 1 PT100 (preheating or media temperature) 011416 1 Main board 039107 1 Display 010433 1 Dissolved oxygen meter (Hannah HI-9145) 010125 1 1-liter visual test vessel with volume markers 2.5 Unpacking and checking Upon receiving the instrument and prior to installing it, check the package for damage and to ensure you have received all of the items listed as follows: Check the outer package for any physical damage. Unpack the instrument and check it for any evidence of damage. Check the goods supplied against your delivery note and purchase order for its completeness. Refer to section 2.4 List of components to make sure that none of the components is missing and that all the components have been received in good condition. If any damage has occurred to the package in transit, inform the manufacturer and the carrier agency IMMEDIATELY. If any evidence of damage to the instrument can be observed, inform the manufacturer IMMEDIATELY. If any component or its parts are missing or damaged, inform the manufacturer IMMEDIATELY. Page 12 of 35

Instrument Installation 3 Instrument Installation 3.1 Assembling Once unpacked, the instrument should be assembled as follows: 1. Position the instrument in its final location on a horizontal plane surface. 2. Remove the load cell locking key by unscrewing it. 3. Put the supplied plastic insert into the load cell cavity. 4. Insert the water collection tray and lid. 5. Connect the media inlet tube into the media inlet at the rear panel of the instrument. Push it firmly. 6. Ensure that the mains switch is switched off. 7. Connect the mains cable to the mains inlet at the rear panel of the instrument. To prevent system damage, ensure that the instrument is not connected to the electrical mains supply. 8. Check that you have the correct power supply for the instrument (see section 2.3 Technical details ). 9. Connect the instrument to the electrical mains supply. 10. Switch on the instrument. 11. Place the media end of the media inlet tube into a container with deionized water. 12. After the startup screen (see below), the Flush System menu appears. Failure to follow these instructions may result in possible damage to the instrument. Do not operate a test until you have performed a flush routine after each time you switch the power off. This resets the instrument. In case of any failure the instrument should be opened by authorized staff only! Before opening the instrument, pull the mains plug. 3.2 Fuses Three fuses on the rear panel protect the instrument as follows: F1 = incoming mains live F2 = incoming mains neutral F3 = PCB and valve assembly Page 13 of 35

3.3 Micro switch Instrument Installation The micro switch at the back of the vessel holder is designed to ensure that a vessel is in place before the filling cycle and at the start of the dispense function. If this switch is not activated during these functions, the instrument will show an error message indicating that the vessel is not in place. Ensure that the vessel is securely held in the vessel holder and that the micro switch is not bent out of shape during the run cycle. The vessels should remain in place throughout the run cycle. 3.4 Safety instructions The instrument is to be wired only to an earthed mains supply socket. The voltage of the available mains supply is to be compared with the indications on the identification plate. ERWEKA accepts no liability in case of false wiring. 3.5 Startup screen The startup screen appears when the instrument is switched on: It shows the firmware version. Please provide it when requesting information, repair, spare parts or during a service visit to the instrument. 3.6 Keypad The display and keypad of the MediPrep 120 are designed to access menus quickly and efficiently. Page 14 of 35

Instrument Installation Buttons Functions Function buttons Used when a command is available in the function line on the display. (F1, F2, F3) The ENTER button To select the current highlighted line on the display to allow value change (the value starts flashing). To confirm the current value and exit the modification (the value stops flashing). Scroll buttons To highlight the needed line of the display by moving the cursor or (arrow keys) highlighted line up or down. To edit the flashing value shown up or down after pressing ENTER. The scroll buttons can be pressed and held (2 sec.) for continuous scrolling or value changing. All data inputs are supported by a beep tone. The beep tone confirms that the command has been accepted and carried out. Page 15 of 35

Main Menu 4 Main Menu This is the main menu of the MediPrep: The MediPrep is designed to be very user-friendly. Each menu item contains instructions on how to take the next step or move back to the previous menus. Where a menu line can be edited, it will be highlighted by a white scroll bar. To change this line, press the ENTER button. Use the scroll up and down buttons (arrow keys) to change the value to the required setting and then press ENTER to confirm this setting. Refer to the chapters below for more information about each menu item. Page 16 of 35

Configuration 5 Configuration Upon completion of the MediPrep 120 installation and setup, the instrument configuration settings should be applied. To apply the configuration settings, select Configuration in the main menu and press ENTER to see the following menu items: Use the arrow keys to scroll through the menu and select the needed item. Once the item is selected, press ENTER to open it. 5.1 Language Use this menu item to select the user language. Select the Language item from the Configuration menu and press ENTER. Select the language you need with the scroll buttons (English or German; other languages are available upon request) and confirm it with ENTER. 5.2 Time Use this menu item to specify the current time. Select the Time item from the Configuration menu and press ENTER. Use the scroll buttons to change the hour, then scroll right to the minutes and adjust the value using the up and down scroll buttons as required. Confirm it by pressing ENTER. 5.3 Date Use this menu item to specify the current date. Select the Date item from the Configuration menu and press ENTER. The day will flash. Use the up and down scroll buttons to select the day, then press the right scroll button to move to the month, then year. Change each value by scrolling up or down and pressing ENTER. Page 17 of 35

5.4 Hard degas time Configuration Upon delivery, the instrument will be set up to ensure that the amount of dissolved oxygen present in the dispensed media is less than 5.5 ppm. It is set to 0 by default as the required degassing is carried out without the hard degas time saving the user time. If you wish to lower the amount of dissolved oxygen from the current level, you can amend the hard degas time from this menu. When the required amount of media has been pumped into the internal chamber, the entry valve to the chamber is closed off but the pump continues to expel air from the chamber. This is the hard degas time. Increasing this time will further reduce the levels of dissolved oxygen in the dispensed media. There is no maximum value set for this parameter but you should not need to use a value above 40 sec. at any time. If you are not getting the required dissolved oxygen levels, refer to chapter 11 Troubleshooting. Select the Hard Degas Time item from the Configuration menu and press ENTER. The current value will flash. Use the up and down scroll buttons to select the required hard degas time and confirm it by pressing ENTER. 5.5 Printout The degasser can be configured so that a test protocol will be printed automatically at the end of each run or you can receive a prompt asking if you wish to receive a printout or not. Alternatively you can switch off the printer. Select the Printout item from the Configuration menu and press ENTER. The current value will flash. Use the scroll buttons to select the required setting (Auto, Prompt, or Off) and confirm it by pressing ENTER. 5.6 Dispense The degasser can be configured to dispense the required media volume at the end of the test in automatic or manual mode: Automatic: the medium is dispensed after the hard degas time directly into the vessel without user intervention. The instrument will check that the vessel is in position at the start of the run and prior to dispense and prompt the user to place the vessel in the vessel holder if the vessel is not present. Do not remove the vessel during dispense. Manual: the instrument prompts the user to press a button prior to dispense confirming that the vessel is in position. Select the Dispense item from the Configuration menu and press ENTER. The current value will flash. Use the scroll buttons to select the required setting (Auto or Manual) and confirm it by pressing ENTER. Please note that by default ERWEKA previously sets the dispense volume to 900 ml ± 1% (related to 35-37 o C). Any other dispense volume requires a change in the offset in the Adjust menu. Page 18 of 35

Adjustment 6 Adjustment Upon completion of the instrument installation, setup and configuration, the adjustment should be carried out. To carry out the adjustment, select Adjust in the main menu and press ENTER to see the following menu items: Note that the values 35 and 38 are not actual temperature values but temperature offset values. The higher the temperature offset value, the higher the media temperature. The higher the load cell offset, the less is being dispensed. 6.1 Setting the dispense temperature The Heater Temp settings specify the heating curve. This curve should be set to heat the media to the required temperature for the volume that you are currently dispensing. There are two settings: one for the lowest output volume of 250 ml and another for the highest output volume of 1000 ml. For any other output volume, the machine calculates an interpolated value between two settings. These will be preset by our engineers prior to shipping but may need some adjustment to allow for your laboratory conditions. The Heater Temp settings are not the actual dispense temperatures. In order to set the correct temperature for your test, use the following procedure. Page 19 of 35

6.1.1 Setting the heater temperature for 250 ml Adjustment To set the heater temperature value for 250 ml: 1. Perform a flush routine. 2. From the Test menu, run a test by degassing and dispensing 250 ml of heated medium with the current settings and discard this. 3. Run a further test with 250 ml of the heated medium and measure the temperature. 4. Enter the Adjust menu and adjust the temperature value in Heater Temp (250ml) up or down by 1 or 2 degrees and run a further test. 5. Repeat the above mentioned until the medium temperature (e.g. 37 C) will be achieved. 6.1.2 Setting the heater temperature for 1000 ml To set the heater temperature value for 1000 ml: 1. Degas and dispense 1000 ml of heated medium with the current settings and discard this. 2. Run a further test with 1000 ml of the heated medium and measure the temperature. 3. Enter the Adjust menu and adjust the temperature value in Heater Temp (1000ml) up or down by 1 or 2 degrees and run a further test. 4. Repeat the above mentioned until the medium temperature (e.g. 37 C) will be achieved. 5. Now check the heated volumes at both 250 ml and 1000 ml and make further adjustments as necessary. Note that the calculation of the dispensed volume should be performed at 25 o C with density of 0.99704 g/ml for water. Use the following equation to determine the weight (dispense accuracy: ±1%): Volume [ml] x Density _Medium [g/ml] = Weight [g] 6.2 Load cell offset (if necessary) This is only required if the machine is found to have an offset in the output volumes. Typically after load cell calibration it might be found that the output volumes tend to have an offset from the expected amounts. This is caused by the pressure applied by the compressor when dispensing has a small effect on the measured load. If such an offset is seen, generate a number of output volumes to obtain an average offset (in grams) from the correct value. The offset is subtracted from the output weight so that, for example, if the output tends to be 10 grams higher than it should be, you need to increase the offset value by 10 grams and vice versa. Adjust the offset appropriately in the Loadcell Offset item of the Adjust menu. Note that the offset should be adjusted after switching on the instrument, the cleaning procedure and every change of the medium volume. This is necessary because the media and their temperatures are density-dependent. Check your results by performing an OQ (see section 8.2 Performing OQ (dispense volume) ). Page 20 of 35

6.3 First load offset (if necessary) Adjustment This is only required if the machine is found to generate incorrect output volumes during the first degassing after switch-on or flush (i.e. when the machine was started with the empty chamber). The machine loads and dispenses a small extra offset weight on these occasions to account for the weight of fluid to fill the outlet pipe work. Obtain an average of the weight of fluid that the offset needs to be adjusted by. Example 1: If every first dispense is 10 grams lower, the offset should be increased by 10 grams. Example 2: If every first dispense is 10 grams higher, the offset should be decreased by 10 grams. Adjust the offset appropriately in the First Load Offset item of the Adjust menu. Page 21 of 35

Test 7 Test When switching on the instrument, it will automatically show the Flush System menu. Before performing the tests, ensure that the MediPrep chamber was emptied. Otherwise, press the empty switch (red button) on the instrument s rare panel. If cleaning solution is different from test media, it is important to discard the first flush. If volume, temperature or media is changed, it is necessary to readjust the offsets in the Adjust menu (see section 6.2 Load cell offset (if necessary) ). The Test item of the main menu allows you choose the settings for the current run as follows: Select the needed item and press ENTER to open it. Refer to the sections below for details. 7.1 Number of vessels This is a number of vessels that need to be degassed and dispensed in this run. You can choose to fill multiple dissolution baths up to 16 vessels. Select the Number of Vessels item from the Test menu and press ENTER. The current value will flash. Use the scroll buttons to select a value between 1 and 16 (holding the scroll button will change the value automatically) and confirm it by pressing ENTER. 7.2 Volume required This is the volume that will be dispensed into each vessel in this run. Select the Volume Required item from the Test menu and press ENTER. The current value will flash. Use the scroll buttons to select a value between 250 ml and 1000 ml (holding the scroll button will change the value automatically) and confirm it by pressing ENTER. Page 22 of 35

7.3 Heater Test You can choose not to heat the medium (e.g. if the medium is already held in a heated ERWEKA Bulk Media tank) Select the Heater item from the Test menu and press ENTER. The current value will flash. Use the scroll buttons to select On or Off and confirm this by pressing ENTER. 7.4 Starting and performing a run Press F3 to start a run from the Test menu and follow the instructions on the screen. The MediPrep 120 will guide you through the run of one vessel at a time. Each vessel should be placed in the vessel holder and will be filled by the instrument. A micro switch is supplied to ensure that the vessel is in place during the run. The lighter indicator will light up to show when the heater is in use. Empty the MediPrep chamber by pressing the empty switch (red button) on the rare panel each time after using the instrument. 7.5 Preheating The instrument will perform preheating of the heaters at the beginning of each test. This will last longer the first time of operation. For this reason, we recommend that you perform one run cycle of 1000 ml prior to using the instrument for your dissolution tester or run a flush routine which preheats the chamber. 7.6 Chamber filling / degassing and dispensing The MediPrep 120 will show animated icons during the chamber filling, degassing and dispensing cycles. These cycles are performed after pressing F3 to start the run. Then the media will be dispensed automatically or manually depending on your settings (see chapter 5 Configuration ). At the run end, the instrument will print out the test protocol (see Appendix) automatically or with a prompt depending on your settings in the Configuration menu. Note that the first dispense after changing the media and cleaning with other media should always be discarded. Ensure that the previous vessel has been removed and that an empty vessel of the correct size is in place during each dispensing. Page 23 of 35

8 Calibration Calibration The MediPrep 120 includes the menus for performing calibration of the load cell, Operation Qualification (volume) and Performance Qualification (dissolved oxygen) as well as for viewing the calibration dates. Select the Calibration item of the main menu to see the following options: Select the required item and press ENTER to open it. Refer to the sections below for details. 8.1 Calibrating the load cell (two-point calibration) This menu guides you through calibration of the internal load cell. Flush the system using the Flush System menu! This is important as it empties the chamber. To calibrate the load cell: 1. Enter the Calibration item in the main menu. 2. Select the Calibrate Loadcell item and press ENTER. 3. Remove the plastic insert from the top of the instrument. 4. Assemble the calibration plate by screwing the plate onto the shaft and firmly tightening. 5. Mount the calibration plate onto the load cell when asked to do so by the instrument (the message Position the Support Weight ) and press ENTER. The calibration plate is screwed into the top of the load cell through the load cell cavity on the top of the instrument. Do not over-tighten. The menus will then guide you through the calibration procedure: 6. Zeroing: tare the load cell with the calibration plate on it. 7. Place the 500 g weight on the calibration plate. 8. The instrument will show the Nominal reading of 500 g and the Actual reading from the load cell. Pressing F3 will set the lower calibration point for the load cell and inform the load cell that 500 g is now being applied to it. 9. You will now be asked to remove the 500 g weight and place the 1000 g weight on the calibration plate. When you have done this, press F3. Page 24 of 35

Calibration 10. The instrument will show the Nominal reading of 1000 g and the Actual reading from the load cell. Pressing F3 will set the upper calibration point for the load cell and inform the load cell that 1000 g is now being applied to it. The load cell is now calibrated. You may choose to repeat this calibration. Two calibrations may be necessary to reach the tolerance of ± 1 g. The instrument now prompts you to remove the support plate and at this time you should reinsert the plastic insert. Then press ENTER. At the end of the calibration, a corresponding calibration protocol is printed (see Appendix). 8.2 Performing OQ (dispense volume) The OQ menu is designed to allow the user check that the volume dispensed by the instrument is within tolerance of ±1 %. Ensure that the first load offset has been adjusted prior to your first OQ! To perform OQ: 1. Enter the Calibration item in the main menu. 2. Select the Perform OQ item and press ENTER. The menus will then guide you through the calibration procedure: Select OQ test parameters: 3. Enter the required weight for this OQ test, e.g. 1000 g at 37 C will weigh 992 g, 900 ml at 37 C will weigh 894 g. OQ tare vessel: Place an empty vessel on a calibrated balance and weigh it. Performing the test: 4. Place the vessel in the vessel holder. 5. Fill the vessel with 1000 ml of the medium from the MD1000. OQ check results: 6. Remove and weigh the vessel complete with the dispensed media. 7. The MediPrep 120 will show the Weight Required (e.g. 894 g ±1 %) and the Actual Weight can be entered by pressing ENTER and using the scroll up and down buttons to select the value shown on the balance 8. Press F3 to confirm the Actual Weight. 9. At the calibration end, a corresponding calibration protocol will be printed that can be signed for Pass or Fail of the instrument (see Appendix). The instrument provides a possibility to perform this test again if required. Page 25 of 35

8.3 Performing PQ (dissolved oxygen) Calibration The PQ menu is designed to allow the user check the level of dissolved oxygen in the dispensed media and enter the received results in the instrument for printing. The MediPrep 120 will provide a sample of dispensed media and the user will be prompted to test this sample with a dissolved oxygen meter (which can be optionally supplied by ERWEKA). To perform PQ: 1. Enter the Calibration item in the main menu. 2. Select the Perform PQ item and press ENTER. The menus will then guide you through the calibration procedure: Select PQ test parameters: 3. Place an empty vessel into the vessel holder. 4. Select the Volume Required. We recommend 1000 ml of the medium. 5. Select whether you wish to switch on the heater for the test. This should be set to ON. 6. Press F3 to start. 7. The instrument will now fill the chamber, degas and dispense the media into the waiting vessel. PQ check results: 8. Remove the vessel and test the media with dissolved oxygen meter (following the instructions of the meter carefully). Press F3. Enter PQ results: 9. The instrument displays the D.O. (Dissolved Oxygen) Level Required < 5.5ppm. Below this, enter the Actual D.O. Level (the flashing value) by pressing the up and down scroll buttons and pressing F3 to confirm it. 10. At the check end, a corresponding calibration protocol will be printed that can be signed for Pass or Fail of the instrument (see Appendix). An additional PQ test can be performed at this time. 8.4 Calibration dates The Calibration Dates menu allows the user check when the last load cell calibration, OQ, PQ and machine service were performed. These dates are stored automatically by the instrument when these functions are performed. The machine service date can only be amended by an ERWEKA trained service engineer (please contact our service department for details). Page 26 of 35

System Flush 9 System Flush The Flush menu can be found in the main menu and should be used to clean through the instrument on a daily basis at the start and end of each day use. It should also be used each time you change your dissolution medium. To flush the instrument: 1. Enter the Flush System item in the main menu. Fill with water: 2. Place an empty 1-liter vessel into the vessel holder and press F3. 3. Place the media inlet tube into deionized water and press F3. 4. The instrument will now fill the system with deionized water. Clear system tubing: 5. When instructed, the media inlet tube should be removed from the deionized water source. Press F3. 6. The system will continue to pump emptying the media inlet tube. Dispensing: 7. The media (just over 1000 ml) held within the chamber will now be dispensed. From the firmware version 1.2 on, the cleaning media is being dispensed in two steps. This ensures no flooding of the vessel. After emptying the vessel, press Continue. 8. Remove the vessel for emptying. Press F3. Approximately 10 ml of the medium will always remain in the instrument. For this reason, you should always flush the system prior to use, at the end of the day use and when changing the media. You may wish to perform the flush routine more than one time to ensure that the instrument and the dispensed media meet your internal requirements for cleaning. You may also opt to empty the chamber (see the subsection 11.1.3 Emptying the system using the empty switch below) prior to using the Flush System menu. This is a matter of your internal procedures. Page 27 of 35

Maintenance and Cleaning 10 Maintenance and Cleaning 10.1 Servicing The MediPrep 120 should receive regular preventative maintenance and servicing to ensure a long life. This should only be performed by an ERWEKA trained engineer. Our engineers are trained to check the correct functioning of all working parts including the load cell, valves, pumps and heaters as well as performing a complete cleaning internally and externally and full validation of the system. Please contact our sales department for a quotation. 10.2 Technical support Contact our service department with any technical questions: Telephone: + 49 6104 69030 Fax: + 49 6104 690340 Email: service@erweka.com 10.3 Daily cleaning tasks Make sure the instrument is cleaned on a regular basis. The MediPrep 120 should be flushed with deionized water at the beginning of each day use, when changing media and at the end of every day use. 10.3.1 Preparing the instrument for operation Switch on the instrument. Perform a flush routine with deionized water. 10.3.2 Replacing the media Perform a flush routine with deionized water when changing the medium. 10.3.3 Shutting down the instrument Perform a flush routine with deionized water. 10.4 Monthly cleaning routine The instrument should be thoroughly cleaned and wiped dry every month. To clean the instrument: 1. Perform a flush routine using the Flush System menu. 2. Disconnect the mains supply. Page 28 of 35

Maintenance and Cleaning 3. Remove the water collection tray with lid and clean with a non-aggressive cleaning agent. A dishwasher may be used for these parts. 4. Wipe down the base unit with a non-aggressive agent. Do not use alcohol or similar solvents since they will damage the surfaces of the instrument! 5. Remove any spillages from around and underneath the water collection tray and the painted parts. 10.5 Cleaning down for storage periods If the instrument is not to be used for a prolonged period (more than 1 week), put a vessel in position and press the red button (empty switch) on the rear panel of the instrument to fully empty the chamber. Page 29 of 35

Troubleshooting 11 Troubleshooting If you encounter a problem while working with the instrument, check this section for possible solutions. For additional help, contact the local technical support service. You may also send a request to the following e-mail address: service@erweka.com. 11.1 Error messages Error messages will inform you about a value or condition that is not consistent with the true or expected value or condition of the system. The error will prevent the instrument from being operated further until the error is rectified. You should read the error message carefully and investigate the cause and possible solutions. You cannot proceed with work without taking actions on the error. 11.1.1 Unit fails to fill / float switch error / time out error The instrument will show this message if the maximum duration for filling has been reached. This informs you that the instrument is not collecting the media into the chamber correctly. The most likely cause for this is that the inlet media tube is either not connected securely or that it is not fully submerged within the media source. To rectify this problem: Check that the media inlet tube is submerged in the media source and that sufficient media exists in the container. Check that the media inlet tube is not pinched or bent/folded. Check that the inline filter (connected to the inlet tube) is clean. Check that the inline filter is securely closed and that the inlet tube push fittings are tightly secured to the inline filter. Check that the media inlet tube is pushed securely into the media inlet on the back of the MediPrep 120. Having checked all the above mentioned settings, empty and flush the system (see the section 11.1.3 Emptying the system using the empty switch below). 11.1.2 Emergency float activation This error message informs you that the instrument is overfilled, has reached the emergency float switch and cut out. To rectify this problem, follow the procedure of emptying the system using the empty switch (see below). Page 30 of 35

11.1.3 Emptying the system using the empty switch Troubleshooting To empty the system using the empty switch: 1. Switch off the instrument using the mains switch on the rear panel and wait 5 seconds. 2. Switch on the instrument. 3. Place an empty vessel in the vessel holder. 4. Press the red button (empty switch) on the rear panel of the instrument. This ejects the media from the chamber. 5. When the chamber is empty, perform a system flush using the Flush System menu (refer to chapter 9 System Flush ). 11.1.4 Warning: drain time out This error message will appear if the instrument is failing to dispense the media correctly. In this case, contact our service department. 11.1.5 Dissolved oxygen content too high / unit not degassing Upon delivery, the instrument is set up to ensure that the amount of dissolved oxygen present in the dispensed media is less than 5.5 ppm. If you wish to lower the amount of dissolved oxygen from the current level, you can amend the hard degas time from this menu. If you are not getting the required dissolved oxygen levels, try increasing the value of the Hard Degas Time in the Configuration menu up to a maximum of 40 sec. If the results are still insufficient, try all connections to ensure that the tube fittings are secure. It is possible that a valve or pump has erred. Contact ERWEKA to rectify this problem. 11.1.6 Printer out of paper To rectify this problem: The printer paper cartridge can be refilled by opening the printer cover (press the Printer Open button). Push together the two pins holding the paper cover end ring. This will release the old cartridge. Place the new ring onto the paper roll pin and feed the free end into the paper slot while pressing the Spool On button. Close the lid. Page 31 of 35

11.2 Moving the instrument Troubleshooting Always ensure that the load cell locking key is in place before moving the instrument! Failure to do this will result in damage to the load cell. 11.3 Opening the instrument Under no circumstances should the back of the instrument be removed by personnel other than ERWEKA service engineers or those of our sales agents! Failure to adhere to this will invalidate the warranty. Page 32 of 35

Appendix Appendix This chapter shows the reports that can be generated by the instrument. Test Report Load Cell Calibration Report OQ Validation Report PQ Validation Report Page 33 of 35

Warranty Warranty The MediPrep 120 is supplied with one-year parts and labor warranty. The warranty will be invalidated if the instrument is repaired, serviced or modified by anybody other than an ERWEKA service engineer or an ERWEKA trained engineer approved in writing by the service department of ERWEKA GmbH. ERWEKA GmbH will not be liable for any damage caused by failure to adhere to the above mentioned. Page 34 of 35

Copyright Copyright The material in this document is the intellectual property of ERWEKA. Any copy or reproduction of this document or its parts without the written permission of and reference to ERWEKA is prohibited and will be prosecuted according to the law. Trademarks All trademarks in this manual are the property of their respective owners. Copyright 20013 by ERWEKA ERWEKA GmbH Ottostrasse 20-22 63150 Heusenstamm Germany Phone: +49-6104-69030 Fax: +49-6104-690340 Page 35 of 35