Toxinometer™ ET-6000 Endotoxin Detection System System contains : analysis module (1), Toximaster® QC7 software (pre-loaded and separate disk), personal laptop computer (1) and validation documents (when applicable). The ET-6000 units are available in “Part 11” and “Non- Part 11” formats with United States and European voltage models provided. Additional analysis modules sold separately. 1

Toxinometer™ ET-6000 Features: Allows for measurement by Turbidimetric, Colorimetric and Gel-clot methods Standard curve calculation function Time course monitoring feature built-in Automatic start of measurement begins with insertion of first test tube provides “walk away” convenience…set it and forget it PC control w/ pre-loaded optimized software 2

* With the Toxinometer™ ET-6000, all 3 methods for BET are available in one system * Samples can be added during measurement * Expandable analysis modules allow for 128 samples to be run simultaneously Flexibility At It’s Best Flexibility at its best 3

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1. Reaction tube insertion position Reaction tubes containing samples are inserted into these positions. The optical system, which is embedded in the bottom of the unit, measures the transmitted light intensity of the solution in the reaction tubes 2.Display LED Displays measurement status LEDStatus of MeasurementResult of Gelation in last Cycle Green blinkingReady to begin measurementsNo Gelation Orange/Red blinkingReady to begin measurementsGelation Green onDuring measurementsNo Gelation yet Orange onDuring measurementsGelation LED offMeasurements are complete or system not yet measuring No Gelation Red onMeasurements are completeGelation All LED’s orange onChanging pre-set temperature. The orange LED turns off when preset temperature changing is complete. 5 5

3. Heater Ready LED This LED indicates that the block temperature is stable at the preset temperature. The light will turn green when the block temperature becomes stable and has reached the preset temperature. 4. Heat Control LED This LED indicates if the block is warming up. When this LED is lit green it indicates that the block is warming up. 5. Power On LED 6. Start Key This key is used to start the measurement at the tube position showing the green LED blinking. By pressing this key after setting the reaction tube, the measurement of the reaction at that position will begin. 7. Reset Key This key is used to cancel the measurement of the latest sample to be started. If you press this key once, the Display LED corresponding to the cancel position will blink. While the Display LED is blinking, press the key once more to cancel the measurement at that position. 8. Stop Key 9. Power Switch 6

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1.USB Connector (UP) This is used to connect the primary ET-6000 analysis module control PC (laptop). 2. USB Connector (DOWN) Used to connect the primary ET-6000 analysis module to additional expansion modules. 3. Cooling Fan Transfer the internally generated heat into the surroundings and stabilizes the device temperature. The ET-6000 automatically controls the fan based on use condition. Keep away from walls and other obstructions. 4. INST. No. Switch (Rotary Switch) Designates number of analysis modules that will be connected. 5. RS-232C Connector (COM) Used only for maintenance purposes. 6. Fuse Holder Houses a 3.15A/250V fuse. 7. Power Connector Please connect only the power cord provided. 8. Ground Connection Terminal 8

Toxinometer ™ ET-6000 – Detection Optics The optical system of the ET-6000 is shown above. Light emitted from a high- illuminance blue LED passes through a first aperture on the light source and enters the reaction mixture in the reaction tube. The light then passes through the reaction mixture, then the second aperture on the silicone photocell and is finally detected by the silicon photocell. 9

Toxinometer™ ET-6000 Light Source High Intensity Blue LED Wavelength of 430nm Low heat Longer duration of life (around 50,000 hours) Low voltage operation Allows for the adjustment of light intensity Eco-friendly (absence of lead and heavy metals) 10

Toxinometer™ ET-6000 Reaction Tubes Limulus Test Tube S PYROSTAR ™ ES-F Single Test Vial 12 x 75mm Sterilized at 250 degrees C Specialized bottom design allows for maximum reading surface Thickness of glass specifically gauged to the Toxinometer ™ for stable light intensity and transmittance Single test: simple, eliminates cross-contamination….just spike your sample and go Single test KTA quantitative range of to 10 EU/ml 11

The ratio of the light intensity l(t) to the light intensity at the onset of the reaction l(o) is defined as R(t), and the threshold R(th) of R(t) is determined. Based on this, the Toxinometer® reads the period from the start of the reaction to the point at which R(t) reaches R(th) as the gelation time (Tg for Turbidimetric method) or the activation time (Ta for Chromogenic method). Toxinometer™ ET-6000 – Measurement Principle 12

Preloaded Toximaster® QC7 Software Program The Toxinometer ™ ET-6000 analysis unit comes with a Dell Laptop computer that is pre- loaded with the Toximaster® QC7 software program, so no software installation is required. The laptop is fully optimized for use with this particular program only, so Wako recommends that no other external programs or software platforms be incorporated onto this unit. A separate software disc is also included with the system. 13

Features of the Toximaster® QC7 Program The Toximaster® QC7 software program provides all of the functions for endotoxin test data processing and report preparation to include: Support of measurement modes complying with BET Simultaneous measurement for FDA test and BET (USP, EP and JP) Assignment of data processing functions to various test groups Simultaneous monitoring of all measurement points Support of various types of standard curves Realization of repeated measurements Functions for entering information on tested samples Time savings in routine processing Storing of test standards 14

Toximaster® Data Files The Toximaster® QC7 software program supports the following four types of data files: 1.Kinetic file (.kinx) – containing the activating time data of the measured wells, the measurement results of calculated concentration and the kinetic data of all measured wells. 2. Results file (.rltx) – contains the same information as the Kinetic file with the exception of the kinetic data 3. Standard Curve file (.calx) – contains the standard curve data only 4. Protocol file (.ptlx) – contains the protocol settings 15

Dell Laptop – Window Opening Screen Toximaster® program shortcut 16

Toximaster® QC7: Load Screen 17

From this location, a series of functions can be selected to facilitate operations from sample preparation to measurement. When the Toximaster® program is initiated, the Welcome Screen will be the first window to appear. 18

Toximaster® QC7: Main Screen Data display view Ribbon Status Bar 19

The Main Screen of the Toximaster® program consists of five major fields, each of which are assigned with specific functions: Application Button – collectively controls the functions associated with the entire application Ribbon – lists the various functions of the Toximaster® QC Part 11. Operation of a specific function is performed by selecting the appropriate button on the ribbon Navigation View – use this view to select the items to be displayed in the data display view such as sample arrangement, well data and time course data. Group reports and standard curve information can also be accessed here. Data Display View – details the items selected in the Navigation View window Status Bar – the name of the person who is logged in, the status of the test record, the set point temperature and the actual temperature of all connected measurement modules are displayed. During measurement, the elapsed time after the start of measurement is also displayed. 20

Navigation View (1) Assay Sample Arrangement The Sample Arrangement display screen consists of the following fields: Information of Selected Wells (left side) – shows the registered test groups, sample types, sample ID’s and settings for the selected wells Sample Arrangement Information (right side) – shows the image of the measurement wells being tested 21

Navigation View (2): Assay Well Data Tg (Time of gelation) While in the Well Data Screen, the progress of measurement data being collected is displayed and can be monitored to include: (1) Sample ID, (2) Activating or Gelation Time, (3) Original Concentration, (4) Elapsed Time, (5) Light Difference Signal and (6) Light Transmission Rate 22

Navigation View (3): Time Course 23

Toximaster® QC7: Standard Curve Standard Curve Graph The standard curve data is plotted and the regression graph is displayed. The concentration and activating time are shown on the horizontal and vertical axes, respectively. Standard Curve Data A list of set concentrations and activating times are displayed. Regression, r The standard regression and correlation coefficient are displayed Interpolation For the standard curve regression, interpolation from concentration to activating time and vice-versa can be performed. When the standard curve is printed, the results of the interpolation can be added. 24

Toximaster® QC7: Assay Group Report 25

Toximaster® QC7: Completed Time Course Print Out 26

Competed Group Report Cover Page Competed Group Report Data Page 27