TOC600 ANALYZER S TANDARD OPERATING P ROCEDURES

Transcription

1 TOC600 ANALYZER S TANDARD OPERATING P ROCEDURES Hach Ultra Analytics 5600 Lindbergh Drive Loveland, Colorado U.S.A. Voice: Fax: Support Hot Line: ANATEL ( ) info@anatel.com Website: Part Number: FG Revision Date: July 2006 Initial Release Date: July 2006 Revision Number: 01 Total Pages: 70

2 Page 2 of 70 The information contained in this document is accurate as of publication. Refer to Hach Ultra Analytics Anatel website at for the most current information on all Anatel products. Copyright 2006 by Hach Ultra Analytics. All rights reserved. Printed in U.S.A. Specifications are subject to change without notice. The information contained in this document is intended to assist Hach Ultra Analytics customers in the use of Anatel products. Any other use of this document or the information contained herein is prohibited, and the reproduction of this document or its contents without the expressed written consent of Hach Ultra Analytics is prohibited. 1 TOC600 Analyzer Standard Operating Procedures (FG580501) Table 1-1 : Revision History Revision Date Comments 01 July 2006 Initial Release. This document contains the following TOC600 Analyzer Standard Operating Procedures (SOPs): Table 1-2 : SOP Contents SOP Title Revision Release 643 1A Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) 01 7/ A System Suitability of the Anatel TOC600 Analyzer 01 7/ Conductivity Calibration of the Anatel TOC600 Analyzer 01 7/ A Temperature Calibration Verification of the Anatel TOC600 Analyzer and Sampling System Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Training on the Principles, Operation & Use of the Anatel TOC600 Analyzer Preventive Maintenance Procedures/Spare Parts Ordering & Inventory Information for the Anatel TOC600 Analyzer 01 7/ / / /06 Anatel TOC600 Analyzer

3 S TANDARD OPERATING PROCEDURE SOP Number: TOC600-1A Distribution List: Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) Objective Calibration provides a confirmation of the accuracy of the TOC values obtained by Anatel online Total Organic Carbon instrumentation. TOC values are determined by measuring the change in conductivity of a high-purity water sample as its organic compounds are oxidized to carbon dioxide inside the instrument s analysis cell. The confirmation procedure subtracts the average of a series of background TOC measurements from the average of a series of user-selected standard measurements (in the form of sucrose). Linear regression is performed on the data and the correlation coefficient (R) and percent slope change (% SC ) is calculated. The calculated R value is recommended to be and 15% of the factory calibration. Note: This Standard Operating Procedure does not attempt to address safety issues associated with its performance. It is the user s responsibility to establish appropriate safety and health practices, as well as determine the applicability of any pertinent regularity restrictions prior to use. Approved by: Reviewed by: Effective date: Part Number: FG Revision Date: July 2006 Initial Release Date: July 2006 Revision Number: 01

4 Page 4 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) 1 Frequency Calibration of the TOC600 Analyzer should be performed routinely according to industry regulations or company protocol thereafter. 2 Scope This procedure is specific for the TOC Calibration of the Anatel TOC600 Analyzer. 3 Reference Documents Anatel TOC600 Analyzer Operators Manual, part number FG , June <643> Total Organic Carbon, United States Pharmacopeia National Formulary USP 25/26-NF 20, January 2002/2003 ISO method 8245 Guidelines for the Determination of Total Organic Carbon. ASTM method D1125, Standard Test Methods for Electrical Conductivity and Resistivity of Water. ASTM method D3694, Practices for Preparation of Sample Containers and for Preservation of Organic Constituents. 4 Materials, Apparatus, and Chemicals Anatel TOC600 Calibration Kit (P/N FG ), including the following: One (1) vial of reagent water blank One (1) vial of 250 ppb C sucrose standard One (1) vial of 500 ppb C sucrose standard One (1) vial of 750 ppb C sucrose standard The Kit should be stored in a refrigerator until ready to use. 5 Instrument Setup and CSV Module installation The TOC600 TOC Analyzer must be networked to a C80 Controller for this procedure. If applicable, disconnect the Analyzer outputs from the process control system while making all calibration measurements. Connect and enable the printer or other associated output device in order to record the results. Before beginning the calibration procedure, the Inlet and Outlet water Tubing will need to be disconnected from the instrument and the CSV (Calibration, Suitability, Validation) module installed. Refer to the Anatel TOC600 Operators Manual for detailed setup instructions. 1) Remove the Calibration Kit from the refrigerator and allow the bottles to warm to room temperature (1-2 hours). 2) Shut off the on-line water supply to instrument and disconnect the Water Inlet and Water Outlet tubes from the instrument. 3) Attached CSV module to the front of the instrument using the supplied mounting bracket (Figure 1). Anatel TOC600 Analyzer SOP Number: TOC600-1A

5 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) Page 5 Fig 1 : TOC600 and attached CSV module CAUTION: I/O fittings may be hot if the sample water was hot. Allow surfaces to cool before touching. 4) Verify that the AC power switch on the CSV Module is in the OFF position. Connect the DC output power connector from the Power Supply to the DC power input jack on the CSV Module and connect the AC power cord to the appropriate power source 5) Connect one end of the Inlet Sample Tube to the CSV Module Water In Port and the other end to the Water Out port on the instrument using the supplied tubing and fittings. 6) Connect the CSV Sample Tube to the Water In port on the instrument and route the other end (with bottle cap) to the CSV module. 7) Attach the Drain Tube to the Water Out Port on the CSV Module and route the other end to an appropriate catch container or liquid drain. 8) Verify that all tubing connections have been made correctly and are tight. 9) Remove the Calibration Standards from the kit and install them in the CSV Module. Starting from the Left, insert the Standards into the numbered locations as follows: #1-(Water Blank), #2-(250 ppb), #3-(500 ppb), #4-(750 ppb). Do not remove the Bottle Caps at this time. TOC600 Analyzer SOP Number: TOC600-1A

6 Page 6 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) 6 TOC Measurements 1) Locate the Certified TOC Values found on the accompanying Certificate of Analysis. Record these TOC Values as required in the SOP TOC600-1A Worksheet Calibration at the end of this Standard Operating Procedure. Fig 2 : Standard Selection Screen Note: Be sure to enter the concentration value that appears on the Certificate of Analysis for each of the sucrose standards to be run. 2) Press the Manual button on the C80 Controller and the display presents three options. 3) Use the Down key to scroll through the selections to choose Calibrations and press Enter. 4) Press the Down key once again to select Calibrate and press Enter. 5) Select TOC Calibrate and press Enter. If more than one Analyzer is networked to the C80 Controller, the screen shows the serial number of the TOC600 Analyzer to be calibrated. Verify that it is the serial number of the appropriate Analyzer and press Enter. The TOC600 delays the start of the TOC Calibration at least five minutes to allow the analysis cell temperature to stabilize. Once stabilized (as reported on the C80 Controller), you can proceed. 6) Verify that the CSV Module is connected and that the power switch is turned Off. Press Enter when ready to proceed. 7) Specify the standards and the number of replicates to be run. Calibration requires at least two replicates at two standard levels. The standard concentrations are set using the Up/ Down keys; a check preceding a standard indicates it will be run. a) With the Standard Selection Screen (Figure 2) displayed, press Enter once. The flashing cursor underscores the check preceding the first standard, 250 ppb Std. b) Press the Up key to select the 250 ppb standard, or press the Down key to deselect the standard. c) Press Enter. If this first standard is deselected, advance to 5.d. If the 250 ppb standard is chosen, the cursor underscores its last digit. Use the Up/Down keys to scroll the display to show the appropriate concentration (found on the accompanying Certificate of Analysis) for the first standard, and then press Enter. d) The flashing cursor underscores the check preceding the second concentration, 500 ppb Std. e) Press Up key to select the 500 ppb standard, or press Down key to deselect the standard. f) Press Enter. If this second standard is deselected, advance to 5.g. If the 500 ppb standard is chosen, the cursor underscores its last digit. Use the Up/Down keys to display the appropriate concentration (found on the accompanying Certificate of Analysis) for this second standard, then press Enter. g) The flashing cursor underscores the check preceding the third concentration, 750 ppb Std. Anatel TOC600 Analyzer SOP Number: TOC600-1A

7 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) Page 7 h) Press Up to select the 750 ppb standard, or press Down to deselect the standard. i) Press Enter. If this third standard is deselected, advance to 5.j. If the 750 ppb standard is chosen, the cursor underscores its last digit. Use the Up/Down keys to display the appropriate concentration (found on the accompanying Certificate of Analysis) for this third standard, then press Enter. j) The flashing cursor now underscores the digit specifying the number of replicates to be run for each selected standard. Use the Up/Down keys to display the appropriate # of reps to be run. Up to three replicates of each standard can be analyzed. k) Press Enter and you are asked if you have entered the "C of A" values. If you have not already done so, press Enter to enter the "C of A" values: once they are entered, pressing Enter allows you to continue. l) If any changes must be made to the standard concentrations or the number of replicates, press Esc followed by Enter to abort the procedure. Immediately press Enter at the Calibrations Menu to re-enter the Standard Selection Menu and continue with TOC Calibration (the previous delays are bypassed). 8) Remove the Water Blank bottle from the CSV Module. 9) Shake the Water Blank Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Insert the CSV Sample Tube into the top of the Water Blank bottle and push the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw cap on to the bottle. 10) Turn the CSV Module Power Switch on, the pump in the CSV Module will cycle on/off automatically as each standard is run. Press Enter to proceed. 11) When analysis of the Water Blank is complete, the instrument displays up to three measurements, which reflect the number of replicates selected. Record these values on the attached WORKSHEET. 12) Press Enter on the C80 Controller and the average of the Water Blank measurements is displayed. Record this value on the WORKSHEET, then press Enter. 13) Remove the 250 ppb bottle from the CSV Module. 14) Shake the 250 ppb Standard Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Remove the CSV Sample Tube/Cap from the Water Blank and insert into the top of the 250 ppb Standard Bottle, pushing the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample TOC600 Analyzer SOP Number: TOC600-1A

8 Page 8 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) Tube screw Cap on to the bottle. Press Enter when ready to proceed. 15) When the analysis is complete, the instrument displays the 250 ppb C Sucrose Standard measurements. Record these values on the attached WORKSHEET. 16) Press Enter and the average of the 250 ppb C Sucrose Standard measurements is displayed. Record this value on the WORKSHEET and press Enter to continue. 17) Remove the 500 ppb bottle from the CSV Module. 18) Shake the 500 ppb Standard Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Remove the CSV Sample Tube/Cap from the 250 ppb Standard and insert into the top of the 500 ppb Standard Bottle, pushing the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw Cap on to the bottle. Press Enter when ready to proceed 19) When the analysis is complete, the instrument displays the 500 ppb C Sucrose Standard measurements. Record these values on the attached WORKSHEET. 20) Press Enter and the average of the 500 ppb C Sucrose Standard measurements is displayed. Record this value on the WORKSHEET and press Enter to continue. 21) Remove the 750 ppb bottle from the CSV Module. 22) Shake the 750 ppb Standard Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Remove the CSV Sample Tube/Cap from the 500 ppb Standard and insert into the top of the 750 ppb Standard Bottle, pushing the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw Cap on to the bottle. 23) When the analysis is complete, the instrument displays the 750 ppb C Sucrose Standard measurements. Record these values on the attached WORKSHEET. 24) Press Enter and the average of the 750 ppb C Sucrose Standard measurements is displayed. Record this value on the WORKSHEET and press Enter to continue. 25) Press Enter to view the calculated average values of the Blank, 250, and 500 ppb standards. Pressing Enter again displays the 750 ppb average. To review the previous set of average data if necessary, press the Up key. 26) Pressing Enter again displays the calculated correlation coefficient (R) and the Pass/Fail status of the Analyzer. Record these results on the attached WORKSHEET. Anatel TOC600 Analyzer SOP Number: TOC600-1A

9 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) Page 9 CAUTION: Pressing Esc results in the previous data being lost. A second Calibration Kit will be required in order to redo the calibration. Note: If the calibration fails, a screen is displayed that states the results are unacceptable. Press Enter on the C80 Controller to repeat the procedure or press Esc to abort the calibration process. 27) If the Calibration is acceptable, then press Enter to save the calibration and print the results. If it's not acceptable, then press Esc to redo the Calibration. 28) This completes the Calibration procedure. If additional procedures (TOC Validation, System Suitability, Conductivity calibration) are to be run, leave the CSV Module connected to the instrument and proceed to the next procedure. 29) To disconnect the CSV Module, remove the CSV Sample Tube/ Cap from the last bottle, re-cap the Standard bottles using the original shipping Caps. Remove the bottles from the CSV Module and follow your company's procedures for proper disposal. Disconnect the Inlet and Outlet tubing from the CSV Module and the Instrument. Reconnect the Instrument Water In and Water Out tubing. Remove the CSM Module from the instrument and press Enter. Return the Instrument to On-Line TOC analysis by pressing View, then Manual, select Modes, press Enter, select Auto TOC and press Enter. 30) To return to the main display, press the View key. 7 Acceptance Note: The calibration will not fail automatically if the correlation coefficient is The correlation coefficient (R) is a user-accepted value only. The TOC600 Analyzer is considered calibrated and within acceptable limits for measuring TOC levels of high-purity water if the absolute value of the slope change (% SC ) is 15% of the factory calibration. It is recommended that the correlation coefficient (R) is Further Action If the TOC600 Analyzer is not within acceptable limits and the TOC calibration was performed according to this Standard Operating Procedure, place the instrument in Self-Clean Mode for at least 30 minutes (refer to the Anatel TOC600 Analyzer Operators Manual), then repeat the procedure using a new Calibration Kit. If the analyzer fails the second calibration, contact Hach Ultra Analytics with the following information: a) Instrument serial number b) Sample resistivity and temperature c) Current and historical TOC data d) Current and historical alarm codes e) A Setup Printout f) Process resistivity and temperature g) Any drain flow observed during sample oxidation h) Any other significant changes in operating conditions TOC600 Analyzer SOP Number: TOC600-1A

10 Page 10 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) SOP TOC600-1A Worksheet Calibration Instrument ID/Serial Number Reagent Water Blank: 250 ppb C sucrose standard 500 ppb C sucrose standard 750 ppb C sucrose standard Reagent Lot Number Certified TOC Value Reagent Water Blank Measurements ppb C ppb C ppb C Average blank measurement 250 ppb C Sucrose Standard Measurements ppb C ppb C ppb C Average 250 ppb C standard measurement 500 ppb C Sucrose Standard Measurements ppb C ppb C ppb C Average 500 ppb C standard measurement 750 ppb C Sucrose Standard Measurements ppb C ppb C ppb C Average 750 ppb C standard measurement Calibration Coefficient (R) TOC Calibration (circle one) Pass / Fail Anatel TOC600 Analyzer SOP Number: TOC600-1A

11 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) Page 11 Comments Checked by Initials: Date: Date: TOC600 Analyzer SOP Number: TOC600-1A

12 Page 12 Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) Notes Anatel TOC600 Analyzer SOP Number: TOC600-1A

13 S TANDARD OPERATING PROCEDURE SOP Number: TOC600-2A Distribution List: System Suitability of the Anatel TOC600 Analyzer Objective System suitability provides a field confirmation of the performance and oxidation efficiency of Anatel online Total Organic Carbon instrumentation. TOC values are determined by measuring the change in conductivity of a high-purity water sample as its organic compounds are oxidized to carbon dioxide inside the instrument s analysis cell. The confirmation procedure compares the average of a series of TOC measurements from an easy to oxidize working standard (in the form of sucrose) to the average of a corresponding series of measurements of a hard to oxidize system suitability solution (in the form of 1,4-Benzoquinone). The calculated TOC content of the system suitability solution should be within ± 15% of the limit response value. Note: This Standard Operating Procedure does not attempt to address safety issues associated with its performance. It is the user s responsibility to establish appropriate safety and health practices, as well as determine the applicability of any pertinent regularity restrictions prior to use. Approved by: Reviewed by: Effective date: Part Number: FG Revision Date: July 2006 Initial Release Date: July 2006 Revision Number: 01

14 Page 14 System Suitability of the Anatel TOC600 Analyzer 1 Frequency System suitability of each TOC600 Analyzer should be confirmed according to industry regulations or company protocol thereafter. This procedure requires that the TOC600 Analyzer has passed a TOC calibration as described in SOP number TOC600-1A, Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) prior to performance. 2 Scope This procedure is specific for the TOC system suitability of the Anatel TOC600 Analyzer. 3 Reference Documents Anatel TOC600 Analyzer Operators Manual, part number FG <643> Total Organic Carbon, United States Pharmacopeia National Formulary USP 25/26-NF 20, June ISO method 8245 Guidelines for the Determination of Total Organic Carbon. ASTM method D1125, Standard Test Methods for Electrical Conductivity and Resistivity of Water. ASTM method D3694, Standard Practices for Preparation of Sample Containers and for Preservation of Organic Constituents. 4 Materials, Apparatus, and Chemicals Anatel TOC600 System Suitability Kit (P/N FG ), including the following: One (1) vial of reagent water blank One (1) vial of 500 ppb C sucrose standard One (1) vial of 500 ppb 1,4-Benzoquinone system suitability solution The Kit should be stored in a refrigerator until ready to use. 5 Instrument Setup and CSV Module installation The TOC600 TOC Analyzer must be networked to a C80 Controller for this procedure. If applicable, disconnect the Analyzer outputs from the process control system while making all calibration measurements. Connect and enable the printer or other associated output device in order to record the results. Before beginning the calibration procedure, the Inlet and Outlet water Tubing will need to be disconnected from the instrument and the CSV (Calibration, Suitability, Validation) module installed. Refer to the Anatel TOC600 Operators Manual for detailed setup instructions. 1) Remove the System Suitability Kit from the refrigerator and allow the bottles to warm to room temperature (1-2 hours). 2) Shut off the on-line water supply to instrument and disconnect the Water Inlet and Water Outlet tubes from the instrument. 3) Attached CSV module to the front of the instrument using the supplied mounting bracket (Figure 1). Anatel TOC600 Analyzer SOP Number: TOC600-2A

15 System Suitability of the Anatel TOC600 Analyzer Page 15 Fig 1 : TOC600 and attached CSV module CAUTION: I/O fittings may be hot if the sample water was hot. Allow surfaces to cool before touching. 4) Verify that the AC power switch on the CSV Module is in the OFF position. Connect the DC output power connector from the Power Supply to the DC power input jack on the CSV Module and connect the AC power cord to the appropriate power source 5) Connect one end of the Inlet Sample Tube to the CSV Module Water In Port and the other end to the Water Out port on the instrument using the supplied tubing and fittings. 6) Connect the CSV Sample Tube to the Water In port on the instrument and route the other end (with bottle cap) to the CSV module. 7) Attach the Drain Tube to the Water Out Port on the CSV Module and route the other end to an appropriate catch container or liquid drain. 8) Verify that all tubing connections have been made correctly and are tight. 9) Remove the System Suitability Standards from the kit and install them in the CSV Module. Starting from the Left, insert the Standards into the numbered locations as follows: #1-(Water Blank), #2-(500 ppb Sucrose), #3-(500 ppb 1-4 Benzoquinone. Do not remove the Bottle Caps at this time. TOC600 Analyzer SOP Number: TOC600-2A

16 Page 16 System Suitability of the Anatel TOC600 Analyzer 6 TOC Measurements 1) Locate the Certified TOC Values found on the accompanying Certificate of Analysis. Record these TOC Values as required on the SOP TOC600-2A Worksheet System Suitability Worksheet at the end of this Standard Operating Procedure). 2) Press the Manual button on the C80 Controller and the display presents three options. 3) Use the Down key to scroll through the selections to choose Calibrations and press Enter. 4) Select Suitability and press Enter. 5) If more than one Analyzer is networked to the C80 Controller, the screen shows the serial number of the TOC600 Analyzer to be calibrated. Verify that it is the serial number of the appropriate Analyzer and press Enter. The TOC600 delays the start of the System Suitability at least five minutes to allow the analysis cell temperature to stabilize. Once stabilized (as reported on the C80 Controller), you can proceed. 6) Verify that the CSV Module is connected and that the power switch is turned Off. Press Enter when ready to proceed. 7) Enter the Certificate of Analysis values for both the lot of Sucrose and 1,4-benzoquinone being used. 8) The standard concentrations are set using the Up/ Down Keys. With the Selection Screen displayed, press Enter. a) The flashing cursor underscores the last digit of the 500 ppb Sucrose standard. b) Use the Up/Down keys to display the appropriate concentration (found on the accompanying Certificate of Analysis) for the Sucrose standard, and then press Enter. c) The flashing cursor next underscores last digit of the 1,4-benzoquinone concentration. d) Use the Up/Down keys to display the appropriate concentration (found on the accompanying Certificate of Analysis) for the 1,4-benzoquinone standard. e) Press Enter. 9) Remove the Water Blank Bottle from the CSV Module. 10) Shake the Water Blank Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Insert the CSV Sample Tube into the top of the Water Blank Bottle and push the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw cap on to the bottle. 11) Turn the CSV Module Power Switch On, the pump in the CSV Module will cycle on/off automatically as each standard is run. Press Enter to proceed. Anatel TOC600 Analyzer SOP Number: TOC600-2A

17 System Suitability of the Anatel TOC600 Analyzer Page 17 12) When analysis of the Water Blank is complete, the instrument displays up to three measurements, which reflect the number of replicates selected. Record these values on the attached WORKSHEET. 13) Press Enter on the C80 Controller and the average of the Water Blank measurements is displayed. Record this value on the WORKSHEET, then press Enter. 14) Remove the 500 ppb Sucrose Standard bottle from the CSV Module. 15) Shake the 500 ppb Standard Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Remove the CSV Sample Tube/Cap from the Water Blank and insert into the top of the 500 ppb Standard bottle, pushing the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw Cap on to the bottle. Press Enter when ready to proceed. 16) When the analysis is complete, the instrument displays the 500 ppb C Sucrose Standard measurements. Record these values on the attached WORKSHEET. 17) Press Enter and the average of the 500 ppb C Sucrose Standard measurements is displayed. Record this value on the WORKSHEET and press Enter to continue. 18) Remove the 500 ppb 1,4-benzoquinone bottle from the CSV Module. 19) Shake the 500 ppb 1,4-benzoquinone Standard Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Remove the CSV Sample Tube/Cap from the 500 ppb Sucrose Standard and insert into the top of the 500 ppb 1,4-benzoquinone Standard bottle, pushing the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw Cap on to the bottle. Press Enter when ready to proceed. 20) When the analysis is complete, the instrument displays the 500 ppb C 1,4-benzoquinone Standard measurements. Record these values on the attached WORKSHEET. 21) Press Enter and the average of the 500 ppb 1,4-benzoquinone Standard measurement is displayed. Record this value on the WORKSHEET. 22) Press Enter to view and print the calculated System Suitability results. Record these results on the attached Worksheet. 23) Press Enter to save the results. TOC600 Analyzer SOP Number: TOC600-2A

18 Page 18 System Suitability of the Anatel TOC600 Analyzer Note: If the system suitability test fails, a screen is displayed that states the results are unacceptable. Press Enter on the C80 Controller to repeat the procedure or press Esc to abort the calibration process. Note: The option to Set TOC Limit equal to Limit Response only is presented when the limit response exceeds the set TOC limit. 24) This completes the System Suitability procedure. If additional procedures (TOC Validation, TOC Calibration, Conductivity calibration) are to be run, leave the CSV Module connected to the instrument and proceed to the next procedure. 25) To disconnect the CSV Module, remove the CSV Sample Tube/ Cap from the last bottle, re-cap the Standard bottles using the original shipping Caps. Remove the bottles from the CSV Module and follow your company's procedures for proper disposal. Disconnect the Inlet and Outlet tubing from the CSV Module and the Instrument. Reconnect the Instrument Water In and Water Out tubing. Remove the CSM Module from the instrument and press Enter. Return the Instrument to On-Line TOC analysis by pressing View, then Manual, select Modes, press Enter, select Auto TOC and press Enter. To return to the main display, press the View key. 26) To return to the main display, press the View key. 7 Calculations Each sucrose and 1,4-benzoquinone replicate analysis is first corrected with the Certificate of Analysis value according to the following equation: Note: Correction of the measured responses for sucrose and 1,4-benzoquinone values by the ratio of 500 and the Certificate of Analysis value corrects for any production variations from the target 500 ppb solutions. 500 Corrected Response = raw response (ppb C) C of A The response efficiency (R E ) is calculated by finding the ratio of the limit response and the system suitability response: Limit Response = r s r w System Suitability Response = r ss r w Where: ( r ss r w ) R E = ( ) 100 r s r w r W = Average TOC response for three measurements of background water used in the preparation of the sucrose standard and the 1,4-benzoquinone system suitability solution in ppb r SS = Certificate of Analysis corrected average TOC response for three measurements of the 1,4-benzoquinone system suitability solution in ppb r S = Certificate of Analysis corrected average TOC response for three measurements of the sucrose stansard solution in ppb R E = response efficiency of the TOC600 Analyzer Anatel TOC600 Analyzer SOP Number: TOC600-2A

19 System Suitability of the Anatel TOC600 Analyzer Page 19 8 Acceptance The TOC600 Analyzer is considered suitable for use in measuring TOC levels of high-purity water if the response efficiency (R E ) is no less than 85% and not more than 115%. 9 Further Action If the TOC600 Analyzer is not within acceptable limits and the system suitability test was performed according to this Standard Operating Procedure, place the instrument in the Self-Clean Mode for at least 30 minutes (refer to the Anatel TOC600 Analyzer Operators Manual), then repeat the procedure using a new System Suitability Kit. If the analyzer fails the second system suitability procedure, repeat both the TOC Calibration (SOP #TOC600-1A, Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) and TOC System Suitability (#TOC600-2A) procedures. If you continue to have problems, contach Hach Ultra Analytics with the following information: a) Instrument serial number b) Sample resistivity and temperature c) Current and historical TOC data d) Current and historical alarm codes e) A Setup Printout f) Process resistivity and temperature g) Any drain flow observed during sample oxidation h) Any other significant changes in operating conditions TOC600 Analyzer SOP Number: TOC600-2A

20 Page 20 System Suitability of the Anatel TOC600 Analyzer Instrument ID/Serial Number SOP TOC600-2A Worksheet System Suitability Reagent Water Blank: 500 ppb C Sucrose Standard 500 ppb C 1,4-Benzoquinone System Suitability Solution Reagent Lot Number Certified TOC Value Reagent Water Reagent Water Measurements ppb C ppb C ppb C Average reagent water measurement (r W ) in ppb C: Sucrose Standard 500 ppb C Sucrose Standard Measurements ppb C ppb C ppb C Average sucrose standard measurement (r S ) in ppb C: 1,4-Benzoquinone Standard 500 ppb C 1,4-Benzoquinone Standard Measurements ppb C ppb C ppb C Average system suitability solution measurement (r SS ) in ppb C: Response Calculations System Response Calculation r SS r W = ppb C Limit Response Calculation r S r W = ppb C Response Efficiency Calculation ( r ss r w ) ( ) 100 r s r w = R E Anatel TOC600 Analyzer SOP Number: TOC600-2A

21 System Suitability of the Anatel TOC600 Analyzer Page 21 Comments Checked by Initials: Date: Date: TOC600 Analyzer SOP Number: TOC600-2A

22 Page 22 System Suitability of the Anatel TOC600 Analyzer Notes Anatel TOC600 Analyzer SOP Number: TOC600-2A

23 S TANDARD OPERATING PROCEDURE SOP Number: TOC600-3 Distribution List: Conductivity Calibration of the Anatel TOC600 Analyzer Objective Conductivity calibration provides a field confirmation of the performance and oxidation efficiency of Anatel online Total Organic Carbon instrumentation. The values are determined by measuring the conductivity of a high-purity water sample prior to oxidation of organic compounds into carbon dioxide inside the instrument s analysis cell. The calibration consists of verifying the cell constant by measuring a solution of known conductivity and determining the instrument s meter accuracy. The instrument s meter accuracy must be within ± 0.1 µs/cm. The cell constant is adjusted to the value of the conductivity standard, and therefore, is always within ± 2%. If the measured values are greater than ± 10% of the original factory value, or ± 5% of the previous calibration, an alarm message displays. Note: This Standard Operating Procedure does not attempt to address safety issues associated with its performance. It is the user s responsibility to establish appropriate safety and health practices, as well as determine the applicability of any pertinent regularity restrictions prior to use. Approved by: Reviewed by: Effective date: Part Number: FG Revision Date: July 2006 Initial Release Date: July 2006 Revision Number: 01

24 Page 24 Conductivity Calibration of the Anatel TOC600 Analyzer 1 Frequency Calibration verification of the conductivity measurement of each TOC600 Analyzer should be confirmed according to industry regulations or company protocol thereafter. 2 Scope This procedure is specific for the conductiivity calibration of the Anatel TOC600 Analyzer. 3 Reference Documents Anatel TOC600 Analyzer Operators Manual, part number FG , June <643> Total Organic Carbon, United States Pharmacopeia National Formulary USP 25/26-NF 20, January 2002/2003 ASTM method D1125, Standard Test Methods for Electrical Conductivity and Resistivity of Water. 4 Materials, Apparatus, and Chemicals 5 Instrument Setup and CSV Module installation Anatel TOC600 Conductivity Kit (P/N FG ) Printer or other suitable serial output device for recording the instrument s conductivity measurements The TOC600 TOC Analyzer must be networked to a C80 Controller for this procedure. If applicable, disconnect the Analyzer outputs from the process control system while making all calibration measurements. Connect and enable the printer or other associated output device in order to record the results. Before beginning the calibration procedure, the Inlet and Outlet water Tubing will need to be disconnected from the instrument and the CSV (Calibration, Suitability, Validation) module installed. Refer to the Anatel TOC600 Operators Manual for detailed setup instructions. 1) Remove the Conductivity Calibration Kit from the refrigerator and allow the bottle to warm to room temperature (1-2 hours). 2) Shut off the on-line water supply to instrument and disconnect the Water Inlet and Water Outlet tubes from the instrument. 3) Attached CSV module to the front of the instrument using the supplied mounting bracket (Figure 1). Anatel TOC600 Analyzer SOP Number: TOC600-3

25 Conductivity Calibration of the Anatel TOC600 Analyzer Page 25 Fig 1 : TOC600 and attached CSV module CAUTION: I/O fittings may be hot if the sample water was hot. Allow surfaces to cool before touching. 4) Verify that the AC power switch on the CSV Module is set in the OFF position. Connect the DC output power connector from the Power Supply to the DC power input jack on the CSV Module and connect the AC power cord to the appropriate power source 5) Connect one end of the Inlet Sample Tube to the CSV Module Water In Port and the other end to the Water Out port on the instrument using the supplied tubing and fittings. 6) Connect the CSV Sample Tube to the Water In port on the instrument and route the other end (with bottle cap) to the CSV module. 7) Attach the Drain Tube to the Water Out Port on the CSV Module and route the other end to an appropriate catch container or liquid drain. 8) Verify that all tubing connections have been made correctly and are tight. 9) Remove the Conductivity Calibration Standard from the kit and install it in the CSV Module. Insert the Conductivity Standard into location #1. Do not remove the Bottle Cap at this time. TOC600 Analyzer SOP Number: TOC600-3

26 Page 26 Conductivity Calibration of the Anatel TOC600 Analyzer 6 Cell Constant Determination Fig 2 : Cell Slope Screen Fig 3 : Conductivity Slope Screen 1) Before continuing with this procedure, retrieve the factory Cell Constant (Cell Slope) and the User Conductivity Slope (So) values and record them on the SOP TOC600-3 Worksheet Conductivity Calibration at the end of this Standard Operating Procedure. a) Press the Setup key on the C80 controller and the display presents four options. b) Select Sensor Setup and press Enter. c) Choose Analysis Setup and press Enter. d) Use the Down arrow key to select More Setup and then press Enter. e) Use the Down arrow key once again to specify Cell Setup, and then press Enter. f) Press the Down key to select Factory Calib and press Enter. g) Choose Cell Slope, press Enter and the Cell Slope is displayed (Figure 2). h) Record the displayed value as the Cell Constant on the attached Worksheet. i) Press Esc twice to return to the previous Cell Setup Menu. j) Use the Up arrow key to select User Calib and press Enter. k) Choose Cond Slope, press Enter and the Conductivity Slope is displayed (Figure 3). l) Record the displayed value as the Conductivity Slope (So) on the attached WORKSHEET. 2) Locate the Certified Conductivity Value found on the accompanying Certificate of Analysis. Record the conductivity Value as required on the WORKSHEET at the end of this Standard Operating Procedure. 3) Press the Manual button on the C80 Controller and the display presents three options. 4) Use the Down key to scroll through the selections to choose Calibrations and press Enter. 5) Press the Down key once again to select Calibrate and press Enter. 6) Select Cond Calibrate and press Enter. If more than one Analyzer is networked to the C80 Controller, the screen shows the serial number of the TOC600 Analyzer to be calibrated. Verify that it is the serial number of the appropriate Analyzer and press Enter. The TOC600 delays the start of the Calibration at least five minutes to allow the analysis cell temperature to stabilize. Once stabilized (as reported on the C80 Controller), you can proceed. 7) Verify that the CSV Module is connected and that the power switch is turned Off. Press Enter when ready to proceed. 8) Enter the concentration value of the Conductivity standard as it appears on the Certificate of Analysis. Anatel TOC600 Analyzer SOP Number: TOC600-3

27 Conductivity Calibration of the Anatel TOC600 Analyzer Page 27 CAUTION: Pressing Esc results in the previous data being lost. A second Calibration Kit will be required in order to redo the calibration. a) With the Conductivity Screen displayed, press Enter and the cursor underscores the last digit of the 100 µs/cm standard. Use the Up/Down arrow keys to display the appropriate concentration (found on the accompanying Certificate of Analysis for this standard. Press Enter. 9) Remove the Conductivity Standard bottle from the CSV Module. 10) Shake the Conductivity Standard k Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Insert the CSV Sample Tube into the top of the Water Blank bottle and push the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw cap on to the bottle. 11) Turn the CSV Module Power Switch On, the pump in the CSV Module will cycle on/off automatically as each Rep is run. Press Enter to proceed. 12) When analysis of the Conductivity Standard is complete, the instrument displays three measurements. Record these values on the attached WORKSHEET. 13) Press Enter on the C80 Controller and the average of the Conductivity Standard measurements is displayed along with the conductivity of the original solution and the differential percentage are displayed. Record these values on the WORKSHEET. Press Enter to continue. 14) If the Calibration is acceptable, press Enter to save the calibration and print these results. If the measured value of the conductivity standard does not agree within ± 10% of the labeled value, an alarm message is displayed. Press Esc to perform the calibration test again. 15) This completes the Calibration procedure. If additional procedures (System Suitability, TOC calibration, TOC Validation) are to be run, leave the CSV Module connected to the instrument and proceed to the next procedure. 16) To disconnect the CSV Module, remove the CSV Sample Tube/Cap from the last bottle, re-cap the Standard bottles using the original shipping Caps. Remove the bottles from the CSV Module and follow your company's procedures for proper disposal. Disconnect the Inlet and Outlet tubing from the CSV Module and the Instrument. Reconnect the Instrument Water In and Water Out tubing. Remove the CSM Module from the instrument and press Enter. Return the Instrument to On-Line TOC analysis by pressing View, then Manual, select Modes, press Enter, select Auto TOC and press Enter. 17) To return to the main display, press the View key. TOC600 Analyzer SOP Number: TOC600-3

28 Page 28 Conductivity Calibration of the Anatel TOC600 Analyzer 7 Calculations The new User Conductivity Slope (S N ) is calculated by dividing the labelled conductivity of the Standard (C L ) by the averaged measured conductivity value of the standard solution (C M ). S N = Where: S N = The User Conductivity Slope determined during the current Conductivity Calibration S C = The change in User Conductivity Slope determined by dividing the new slope by the last slope and represented by the equation: C L C M S C = S N % S O S O = The User Conductivity Slope that was determined during the last successful conductivity calibration C L = The labelled conductivity of the Standard C M = The analyzer s average measured conductivity value C K = The percent difference between the actual conductivity standard value and the Anatel TOC600 s measured conductivity value in µs/cm. 8 Acceptance Note: USP Method <645> requires the cell constant to be known within ± 2%. To ensure this is the case, if the conductivity calibration solution is measured within ± 5% of the previous calibration value, then the new cell constant (slope) is used in the current calibration, and saved as the cell slope for future calibrations. This calibration of the Anatel TOC600 Analyzer for conductivity measurement provides both a confirmation of the cell constant and meter accuracy of the instrument. The Analyzer is considered calibrated and within acceptable limits for the purpose of measuring conductivity levels of high-purity water if the measured slope change using the standard solution has not changed more than ± 5% from the previous calibration or ±10% from the factory calibration. Anatel TOC600 Analyzer SOP Number: TOC600-3

29 Conductivity Calibration of the Anatel TOC600 Analyzer Page 29 9 Further Action If the TOC600 Analyzer is not within acceptable limits and the conductivity calibration was performed according to this Standard Operating Procedure, place the instrument in Self-Clean Mode for at least 30 minutes (refer to the Anatel TOC600 Analyzer Operators Manual), then repeat the calibration procedure. If the analyzer fails the second calibration, contact Hach Ultra Analytics with the following information: a) Instrument serial number b) Sample resistivity and temperature c) Current and historical TOC and conductivity data d) Current and historical alarm codes e) A Setup Printout f) Process resistivity and temperature g) Any drain flow observed during sample oxidation h) Any other significant changes in operating conditions TOC600 Analyzer SOP Number: TOC600-3

30 Page 30 Conductivity Calibration of the Anatel TOC600 Analyzer Instrument ID/Serial Number SOP TOC600-3 Worksheet Conductivity Calibration Current User Conductivity Slope (S O ): Cell Constant (Cell Slope): Conductivity Calibration Measured Value of the Conductivity Standard: µs/cm µs/cm µs/cm Average measured conductivity value (C M ): µs/cm Value of the Conductivity Standard from the Certificate of Analysis (C L ) in µs/cm: Show User Conductivity Slope Calculation (S N ): C L = S N C M Is S N and is S N 1.104? Yes / No Conductivity Calibration Status: Pass / Fail Comments: Checked by Initials: Date: Date: Anatel TOC600 Analyzer SOP Number: TOC600-3

31 S TANDARD OPERATING PROCEDURE SOP Number: TOC600-4 Distribution List: Temperature Calibration Verification of the Anatel TOC600 Analyzer Objective Temperature calibration verification provides a field confirmation of the accuracy of the temperature values reported by Anatel online Total Organic Carbon instrumentation. The values are determined by measuring the temperature of a high-purity water sample flowing through the instrument s analysis cell. The verification subtracts a stable instrument reading from that obtained by a calibrated temperature measurement device. The difference should be no more than ±1 C. Note: This Standard Operating Procedure does not attempt to address safety issues associated with its performance. It is the user s responsibility to establish appropriate safety and health practices, as well as determine the applicability of any pertinent regularity restrictions prior to use. Approved by: Reviewed by: Effective date: Part Number: FG Revision Date: July 2006 Initial Release Date: July 2006 Revision Number: 01

32 Page 32 Temperature Calibration Verification of the Anatel TOC600 Analyzer 1 Frequency Calibration verification of the temperature measurement of the TOC600 Analyzer should be routinely confirmed according to industry regulations or company protocol thereafter. This SOP is not meant to be a calibration method. All Anatel instruments are calibrated for temperature at the factory and no adjustments can be made by the user. 2 Scope This procedure is specific for the temperature measurements of the Anatel TOC600 Analyzer. 3 Reference Documents Anatel TOC600 Analyzer Operators Manual, part number FG , June Materials, Apparatus, and Chemicals Certified temperature measurement device with an accuracy of ±0.25 C or better. High-purity water with a flow rate of at least 100 ml/minute 5 Temperature Calibration Verification Temperature Measurement This procedure is performed in the process area. 1) Referring to the TOC600 Analyzer Operators Manual, put the TOC600 Analyzer to be verified into purge mode. 2) Allow the process water to flow through the instrument until its displayed temperature reading stabilizes to ±0.1 C. Measure the water flow rate exiting from the analyzer s Water Out port with a graduated cylinder and verify that the flow rate is at least 60 ml/minute. 3) Place the calibrated temperature measurement device into the water stream entering the analyzer s Water In port (Figure 1) and allow the temperature to equilibrate. The temperature probe must be no further than three inches from the analyzer s Water In port. 4) When the display on the calibrated temperature measurement device has stabilized, record the reference reading (T Ref ) on the SOP TOC600-4 Worksheet Temperature Calibration Verification at the end of this procedure. Also immediately record the sample water temperature reading reported in the analyzer display (T Anatel ). 5) Return the analyzer to Auto TOC mode. Anatel TOC600 Analyzer SOP Number: TOC600-4

33 Temperature Calibration Verification of the Anatel TOC600 Analyzer Page 33 High-purity water system Optional Isolation Valve (user-supplied) Note: The reading must be taken no further than 3" from the Analyzer's Water In port to prevent a significant temperature drop between the Analyzer and the calibrated measurement device. Calibrated Temperature Measurement Device 25 C TOC 1 ppb P3 WATER IN 3" or less ANATEL TOC600 WATER OUT TOC600 Analyzer To Drain Fig 1 : TOC600 Analyzer Diagram 6 Calculations The difference (T Diff ) between the temperature measurements is calculated by subtracting the analyzer s temperature reading (T Anatel ) from the temperature reading of the certified measurement device (T Ref ). Where: T Diff = T Ref T Anatel T Diff = The difference between the certified temperature measurement and the analyzer s temperature measurement in C. T Ref = The sample water temperature reading of the certified measurement device in C. T Anatel = The sample water temperature reading of the analyzer at the time the reference temperature was recorded in C. 7 Acceptance The TOC600 Analyzer is considered within acceptable limits for the purpose of measuring temperature levels of high-purity water is the difference between the two measurements (T Diff ) is within ±1 C. TOC600 Analyzer SOP Number: TOC600-4

34 Page 34 Temperature Calibration Verification of the Anatel TOC600 Analyzer 8 Further Action If the TOC600 Analyzer is not within acceptable limits and the temperature calibration verification was performed according to this Standard Operating Procedure, place the instrument in Purge Mode (refer to the Anatel TOC600 Analyzer Operators Manual) for at least 30 minutes maintaining a flow rate through the instrument cell of at least 100 ml/minute. Repeat the verification procedure. If the analyzer fails the second verification procedure, contact Hach Ultra Analytics with the following information: a) Instrument serial number b) Sample resistivity and temperature c) Current and historical TOC and conductivity data d) Current and historical alarm codes e) A Setup Printout f) Process resistivity and temperature g) Any drain flow observed during sample oxidation h) Any other significant changes in operating conditions Anatel TOC600 Analyzer SOP Number: TOC600-4

35 Temperature Calibration Verification of the Anatel TOC600 Analyzer Page 35 SOP TOC600-4 Worksheet Temperature Calibration Verification Instrument ID/Serial Number Certified Temperature Measurement Device Number: Date of last certification: Temperature of analyzer inlet water reported by the certified temperature measurement device (T Ref ): C Analyzer temperature reading (T Anatel ): C Show T DIFF Calculation T Ref T Anatel = T Diff Comments: Checked by Initials: Date: Date: TOC600 Analyzer SOP Number: TOC600-4

36 Page 36 Temperature Calibration Verification of the Anatel TOC600 Analyzer Notes Anatel TOC600 Analyzer SOP Number: TOC600-4

37 S TANDARD OPERATING PROCEDURE SOP Number: TOC600-5A Distribution List: Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Objective Validation of the TOC600 Analyzer s TOC calibration is provided by analyzing user-selected concentrations of sucrose validation standards after a TOC calibration has been performed. The instrument response for the validation standard must have a deviation of less than 15% of the calibrated response to be considered acceptable. Note: This Standard Operating Procedure does not attempt to address safety issues associated with its performance. It is the user s responsibility to establish appropriate safety and health practices, as well as determine the applicability of any pertinent regularity restrictions prior to use. Approved by: Reviewed by: Effective date: Part Number: FG Revision Date: July 2006 Initial Release Date: July 2006 Revision Number: 01

38 Page 38 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) 1 Frequency Validation of each TOC600 Analyzer should be routinely confirmed according to industry regulations or company protocol thereafter. A valid TOC Calibration must be completed on the instrument as described in SOP number TOC600-1A, Calibration of the Anatel TOC600 Analyzer (Sucrose Standards) before performing this procedure. 2 Scope This procedure is specific for the TOC validation of the Anatel TOC600 Analyzer. 3 Reference Documents Anatel TOC600 Analyzer Operators Manual, part number FG , June ISO method 8245 Guidelines for the Determination of Total Organic Carbon. ASTM method D1125, Standard Test Methods for Electrical Conductivity and Resistivity of Water. ASTM method D3694, Standard Practices for Preparation of Sample Containers and for Preservation of Organic Constituents. 4 Materials, Apparatus, and Chemicals The Anatel kit used to perform the validation depends on the number of standards being used. The TOC600 Validation Kit contains supplies for a single standard, while the TOC600 Calibration Kit allows as many as three standards to be used. In either case, store the kit under refrigeration until ready for use. 5 Instrument Setup and CSV Module installation Anatel TOC600 Validation Kit (P/N FG ) One (1) vials of reagent water blank One (1) vial of 500 ppb C sucrose standard Anatel TOC600 Calibration Kit (P/N FG ) One (1) vial of reagent water blank One (1) vial of 250 ppb C sucrose standard One (1) vial of 500 ppb C sucrose standard One (1) vial of 750 ppb C sucrose standard The TOC600 TOC Analyzer must be networked to a C80 Controller for this procedure. If applicable, disconnect the Analyzer outputs from the process control system while making all calibration measurements. Connect and enable the printer or other associated output device in order to record the results. Before beginning the calibration procedure, the Inlet and Outlet water Tubing will need to be disconnected from the instrument and the CSV (Calibration, Suitability, Validation) module installed. Refer to the Anatel TOC600 Operators Manual for detailed setup instructions. Anatel TOC600 Analyzer SOP Number: TOC600-5A

39 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Page 39 1) Remove the TOC Validation Kit from the refrigerator and allow the bottles to warm to room temperature (1-2 hours). 2) Shut off the on-line water supply to instrument and disconnect the Water Inlet and Water Outlet tubes from the instrument. 3) Attached CSV module to the front of the instrument using the supplied mounting bracket (Figure 1). Fig 1 : TOC600 and attached CSV module CAUTION: I/O fittings may be hot if the sample water was hot. Allow surfaces to cool before touching. 4) Verify that the AC power switch on the CSV Module is set in the OFF position. Connect the DC output power connector from the Power Supply to the DC power input jack on the CSV Module and connect the AC power cord to the appropriate power source 5) Connect one end of the Inlet Sample Tube to the CSV Module Water In Port and the other end to the Water Out port on the instrument using the supplied tubing and fittings. 6) Connect the CSV Sample Tube to the Water In port on the instrument and route the other end (with bottle cap) to the CSV module. 7) Attach the Drain Tube to the Water Out Port on the CSV Module and route the other end to an appropriate catch container or liquid drain. 8) Verify that all tubing connections have been made correctly and are tight. TOC600 Analyzer SOP Number: TOC600-5A

40 Page 40 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) 9) Remove the Validation Standards from the kit and install them in the CSV Module. Starting from the Left, insert the Standards into the numbered locations as follows: #1-(Water Blank), #2-(500 ppb). If a multipoint validation is run, install the Standards starting from the left in order of increasing concentration (Blank, 250 ppb, 500 ppb, 750 ppb). Do not remove the Bottle Caps at this time. 6 TOC Measurements 1) Locate the Certified TOC Values found on the accompanying Certificate of Analyses. Record these TOC Values as required on the SOP TOC600-5A Worksheet Validation (500 ppb C Standard) or SOP TOC600-5A Worksheet Validation (250, 500, & 750 ppb C Standards) at the end of this procedure. Fig 2 : Valedate Screen 2) Press the Manual button on the C80 Controller and the display presents three options. 3) Use the Down key to scroll through the selections to choose Calibrations and press Enter. 4) Press the Down key twice again to select Validate and press Enter. 5) If more than one Analyzer is networked to the C80 Controller, the screen shows the serial number of the TOC600 Analyzer to be calibrated. Verify that it is the serial number of the appropriate Analyzer and press Enter. The TOC600 delays the start of the TOC Calibration at least five minutes to allow the analysis cell temperature to stabilize. Once stabilized (as reported on the C80 Controller), you can proceed. 6) Verify that the CSV Module is connected and that the power switch is turned Off. Press Enter when ready to proceed. 7) Specify the 500 ppb standard and the number of replicates to be run. Set standard concentration using the Up/ Down keys; a check preceding a standard indicates it will be run. a) With the Validate Screen (Figure 2) displayed, press the Up arrow key twice. Press Enter and the cursor underscores the last digit of the 500 ppb standard. Use the Up/Down arrow keys to display the appropriate concentration (found on the accompanying Certificate of Analysis for this standard. b) Press Enter twice and the flashing cursor underscores the digit specifying the number of replicates to be run for the 500 ppb C standard. Use the Up/Down arrow keys to display the appropriate # of reps to be run. Up to three replicates of each standard can be analyzed. c) If any changes must be made to the standard concentrations or the number of replicates, press Esc followed by Enter to abort the procedure. Immediately press Enter at the Calibrations Menu to re-enter the Standard Selection Menu and continue with TOC Validation (the previous delays are bypassed). Anatel TOC600 Analyzer SOP Number: TOC600-5A

41 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Page 41 8) Remove the Water Blank bottle from the CSV Module. 9) Shake the Water Blank Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Insert the CSV Sample Tube into the top of the Water Blank bottle and push the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw cap on to the bottle. 10) Turn the CSV Module Power Switch On, the pump in the CSV Module will cycle on/off automatically as each standard is run. Press Enter to proceed. 11) When analysis of the Water Blank is complete, the instrument displays up to three measurements, which reflect the number of replicates selected. Record these values on the attached WORKSHEET. 12) Press Enter on the C80 Controller and the average of the Water Blank measurements is displayed. Record this value on the WORKSHEET, then press Enter. 13) Remove the 500 ppb bottle from the CSV Module. 14) Shake the 500 ppb Standard Bottle vigorously for at least five seconds, re-install the bottle back into the CSV bottle tray, and remove the screw cap. Remove the CSV Sample Tube/Cap from the Water Blank and insert into the top of the 500 ppb Standard bottle, pushing the tube down until it is near the bottom of the bottle. Secure the Sample Tube in place by tightening the Sample Tube screw Cap on to the bottle. Press Enter when ready to proceed. 15) When the analysis is complete, the instrument displays the 500 ppb C Sucrose Standard measurements. Record these values on the attached WORKSHEET. 16) Press Enter and the average of the 500 ppb C Sucrose Standard measurements is displayed. Record this value on the WORKSHEET. 17) Repeat Steps For each additional sucrose validation standards required. The Water Blank is analyzed only once at the beginning of the process and the Blank average is subtracted from the Replicate average of each sucrose validation level. The results are displayed once all analyses are completed. 18) Press Enter twice and the results are averaged and then reported in the form of a ppb response and deviation percentage. The instrument passes the Validation Test if the response has a deviation of less than 15% from the given Sucrose Standard value. Press Enter to continue. 19) Press Enter to accept the test results and initiate a printout of the data. Record the results on the attached Worksheet. TOC600 Analyzer SOP Number: TOC600-5A

42 Page 42 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Note: If the validation fails, a screen is displayed that states the results are unacceptable. Press Enter on the C80 Controller to repeat the procedure or press Esc to abort the validation process. 20) This completes the Validation procedure. If additional procedures (System Suitability, Conductivity calibration) are to be run, leave the CSV Module connected to the instrument and proceed to the next procedure. 21) To disconnect the CSV Module, remove the CSV Sample Tube/ Cap from the last bottle, re-cap the Standard bottles using the original shipping Caps. Remove the bottles from the CSV Module and follow your company's procedures for proper disposal. Disconnect the Inlet and Outlet tubing from the CSV Module and the Instrument. Reconnect the Instrument Water In and Water Out tubing. Remove the CSM Module from the instrument and press Enter. Return the Instrument to On-Line TOC analysis by pressing View, then Manual, select Modes, press Enter, select Auto TOC and press Enter. 22) To return to the main display, press the View key. 7 Calculations The percentage of deviation (% D ) is calculated by dividing the validation response (r V ) minus the reagent water blank response (r W ), by the certified TOC value (r C ) from the Certificate of Analysis for the validation standard. Where: ( r % V r W ) D = ( ) r C r V = Average TOC response for three measurements of the sucrose validation standard. r W = Average TOC response for three measurements of background water used in the preparation of the validation standard. r C = Certified TOC value from the Certificate of Analysis for the validation standard. 8 Acceptance The instrument response for the Carbon Sucrose Validation Standard must have a deviation of less than ±15% from the Certificate of Analysis validation standard value to be considered acceptable. Anatel TOC600 Analyzer SOP Number: TOC600-5A

43 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Page 43 9 Further Action If the TOC600 Analyzer is not within acceptable limits and the validation was performed according to this Standard Operating Procedure, place the instrument in Self-Clean Mode for at least 30 minutes (refer to the Anatel TOC600 Analyzer Operators Manual), then repeat the procedure using a new Validation Kit. If the analyzer fails the second validation procedure, repeat both the TOC Calibration (SOP #TOC600-1A) and the TOC Validation (SOP #TOC600-5A) procedures. If problems continue, contact Hach Ultra Analytics with the following information: a) Instrument serial number b) Sample resistivity and temperature c) Current and historical TOC data d) Current and historical alarm codes e) A Setup Printout f) Process resistivity and temperature g) Any drain flow observed during sample oxidation h) Any other significant changes in operating conditions TOC600 Analyzer SOP Number: TOC600-5A

44 Page 44 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) SOP TOC600-5A Worksheet Validation (500 ppb C Standard) Instrument ID/Serial Number Reagent Water Blank: 500 ppb C Validation Standard (r C ): Reagent Lot Number Certified TOC Value Background Water Measurements ppb C ppb C ppb C Average Background Measurement (r W ): ppb C 500 ppb C Sucrose Validation Standard Measurements ppb C ppb C ppb C Average 500 ppb C Sucrose Standard Measurement (r V ): ppb C Show Validation Response Calculation: r V r W = ppb C Show Percent Deviation (% D ) Calculation: ( r V r W ) ( r C ) = % D Comments: Checked by Initials: Date: Date: Anatel TOC600 Analyzer SOP Number: TOC600-5A

45 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Page 45 SOP TOC600-5A Worksheet Validation (250, 500, & 750 ppb C Standards) Instrument ID/Serial Number Reagent Water Blank: Validation Standard (r C ): Validation Standard (r C ): Validation Standard (r C ): Reagent Lot Number Certified TOC Value Background Water Measurements ppb C ppb C ppb C Average Background Measurement (r W ): ppb C 250 ppb C Sucrose Validation Standard Measurements ppb C ppb C ppb C Average 250 ppb C Sucrose Standard Measurement (r V ): ppb C 500 ppb C Sucrose Validation Standard Measurements ppb C ppb C ppb C Average 500 ppb C Standard Standard Measurement (r V ): ppb C 750 ppb C Sucrose Validation Standard Measurements ppb C ppb C ppb C Average 750 ppb C Standard Standard Measurement (r V ): ppb C TOC600 Analyzer SOP Number: TOC600-5A

46 Page 46 Validation of the Anatel TOC600 Analyzer (Sucrose Standards) Show 250 ppb C Validation Response Calculation: r V r W = ppb C Show Percent Deviation (% D ) Calculation: ( r V r W ) % ( r C ) = % D Show 500 ppb C Validation Response Calculation: r V r W = ppb C Show Percent Deviation (% D ) Calculation: ( r V r W ) % ( r C ) = % D Show 750 ppb C Validation Response Calculation: r V r W = ppb C Show Percent Deviation (% D ) Calculation: ( r V r W ) % ( r C ) = % D Comments: Checked by Initials: Date: Date: Anatel TOC600 Analyzer SOP Number: TOC600-5A

47 S TANDARD OPERATING PROCEDURE SOP Number: TOC600-6 Distribution List: Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer Objective This document provides a general guide for the training of personnel associated with the use and operation of the Anatel TOC600 Analyzer. The TOC600 is designed for the on-line measurement of conductivity, temperature and Total Organic Carbon in pharmaceutical high-purity water systems. User training supplements are recommended for each individual system. Note: This Standard Operating Procedure does not attempt to address safety issues associated with its performance. It is the user s responsibility to establish appropriate safety and health practices, as well as determine the applicability of any pertinent regularity restrictions prior to use. Approved by: Reviewed by: Effective date: Part Number: FG Revision Date: July 2006 Initial Release Date: July 2006 Revision Number: 01

48 Page 48 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer 1 Scope This training document is specific to the Anatel TOC600 Analyzer. It begins with a synopsis of the United States Pharmacopeia s (USP) rationale for the use of Total Organic Carbon (TOC) and conductivity in the determination of the suitability of high-purity water for certain pharmaceutical purposes. This summary is followed by a basic discussion of the TOC and conductivity measurement techniques employed by the Anatel TOC600 Analyzer. Finally, the use and operation of the TOC600 Analyzer, as well as the associated sampling system for pharmaceutical water applications, is reviewed. 2 Reference Documents Anatel TOC600 Analyzer Operators Manual, part number FG , June <643> Total Organic Carbon ; United States Pharmacopeia National Formulary USP 25/26 NF 20, January 2002/2003. <645> Water Conductivity ; United States Pharmacopeia National Formulary USP 25/26 NF 20, January 2002/2003. ASTM method D1125 Standard Test Methods for Electrical Conductivity and Resistivity of Water. Soli, T.C., in Pharm Tech Conference Proceedings 94, Atlantic City, N.J., Sept , 1994, pp , Advanstar Communications, Eugene, Oregon Revising the Chemical Specifications and Microbial Discussion in the United States Pharmacopeia. Anatel Standard Operating Procedure #TOC600 1A: Calibration of the Anatel TOC600 Analyzer. Anatel Standard Operating Procedure #TOC600 2A: System Suitability of the Anatel TOC600 Analyzer. Anatel Standard Operating Procedure #TOC600 3: Conductivity Calibration of the Anatel TOC600 Analyzer. Anatel Standard Operating Procedure #TOC600 4: Temperature Calibration of the Anatel TOC600 Analyzer. 3 USP Measurements of Water Quality Attributes High-purity water, such as Purified Water (PW) and Water-for-Injection (WFI), represents the largest volume raw material used bythe pharmaceutical industry today. Anatel TOC600 Analyzer SOP Number: TOC600-6

49 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer Page Old Tests Prior to November 1996, the tests required for PW and WFI by the United States Pharmacopeia (USP) were: Test Date Introduced Sulfate 1840 Calcium 1840 Carbon Dioxide 1850 Chloride 1890 Ammonia 1890 Oxidizable Substances 1890 Heavy Metals 1900 Total Solids 1947 Coliforms 1947 ph 1970 Bacterial Endotoxins (BET) 1983 Most of these chemical tests lack standards, are antiquated, subjective, insensitive, labor-intensive, unusable for process control, inapplicable to on-line measurement, involve tedious wet chemistry, and provide slow data turnaround time. 3.2 New Tests The Water Quality Committee of the Pharmaceutical Research and Manufactures of America (PhRMA), in cooperation with the USP staff and members of the Committee of Revisions, conducted a comprehensive review and evaluation of the various USP regulations relating to pharmaceutical grades of water. Recommendations were proposed to revise the compendia s monographs, test chapters and general information chapter for water specifications and testing. The following changes were made to the USP Water Monograph for PW and WFI: Current Revised Calcium Conductivity Sulfate Conductivity Chloride Conductivity Ammonia Conductivity Carbon Dioxide Conductivity ph Retain with Conductivity Oxidizable Substances TOC BET (WFI only) Retain Heavy Metals Delete Total Solids Delete Coliforms Delete TOC600 Analyzer SOP Number: TOC600-6

50 Page 50 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer The measurement of conductivity will replace the USP wet chemical inorganic ion limit tests for Ca ++, SO4 =, Cl, NH 3, and CO 2. The existing ph test will be retained. If necessary, the ph measurement will be used to correct the conductivity measurement for absorption of atmospheric carbon dioxide. The measurement of TOC replaces the current USP oxidizable substances limit test for the detection of organic compounds in water. The TOC test is non-selective, sensitive, rapid, quantitative and highly reproducible. System suitability rather than a specific method of TOC analysis will be used to validate this measurement. Conductivity and TOC measurements can be automated and are well suited for on-line monitoring. The Heavy Metals, Total Solids, and Coliforms tests were deleted. Method-linked action levels are to be established by the user based on the application and product being manufactured. Viable microbial testing is to be used for both process control and QC. No best test method for all water systems has been established: It is up the user to establish the best sampling and methods for the particular water system. 4 Conductivity Conductivity in water is a measure of the ability of the water to carry an electrical current. Water molecules dissociate into ions as a function of ph and temperature. Some gases, most notably carbon dioxide, readily dissolve in water to form ions that affect both the conductivity and the ph of the water. These ions are regarded as intrinsic to the water. Water conductivity is also influenced by the presence of extraneous ions such as those included in the present USP water test requirements. The conductivity of water is a summation of the contributions of all the ions present. The combined conductivity of the intrinsic and extraneous ions varies as a function of ph and temperature and is the basis for the proposed USP conductivity specifications for PW. 4.1 Measurement Conductivity is determined by applying an alternating current voltage across two electrodes and measuring the electrical resistance of the segment of solution between the electrodes. The size of the electrodes and the distance between them influences this reading and defines the measurement cell constant. Note: A cell with electrode dimensions of 1 cm by 1 cm, with electrodes spaced 1 cm apart, possesses a cell constant of 1 cm -1. Cell Constant = distance between electrodes (cm) area of electrodes (cm 2 ) For a constant distance between the electrodes, the lower the conductivity (and the higher the resistivity) of the liquid being measured, the larger the area of electrodes needed for accurate measurement. Conversely, for a constant area of the electrodes under the same conductivity/resistivity conditions, less distance is required between the two electrodes for accurate measurement. Anatel TOC600 Analyzer SOP Number: TOC600-6

51 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer Page Units The relationship between conductivity and resistivity is a mathematical reciprocal. There is no difference in the instrumentation used to obtain the measurements. The units of measurement are ohms for resistivity and mhos or Siemens for conductivity: Contuctance = L = = = mhos = Siemens R ohms Since conductance may be measured by many electrode configurations, the units of conductivity (specific conductance) are used to normalize the effect of the cell dimensions. Conductivity (specific conductance) is the measured conductance multiplied by the cell constant: Conductivity (Specifice Conductance) = measured conductance (Siemens) cell contant (cm 1 ) = Siemens cm 4.3 Temperature Temperature has a significant effect on the measured conductivity of a liquid. For dilute solutions, the higher the temperature, the more conductive (less resistive) the solution becomes. Most conductivity specifications are established for solutions at a temperature of 25 C, although measurements are seldom taken at this exact temperature. Modern instrumentation includes a temperature compensation function which calculates the specific conductance value that would be observed at 25 C regardless of the temperature of the solution being measured. Since conductivity is a function of the contributions of all the different ions in solution, there is no single temperature compensation factor that is correct for all solutions. 4.4 Validation of the Measurement Device High-purity water has a very low conductivity and high resistivity. The theoretical specific conductance of pure water at 25 C is µs/cm ( S/cm). The specific resistivity of this water is Mohm-cm (18,150,000 ohm-cm). When the conductivity of highpurity water is measured at temperatures other than 25 C, only temperature compensation algorithms within microprocessor-controlled instruments are adequate to provide reasonable estimates of the true conductivity at 25 C. The ability of a conductivity measurement system to provide accurate measurements depends on the accuracy of the instrument and the accuracy of the cell constant used to convert the measurement value to specific conductance units. If measurements are made at temperatures other than 25 C, the temperature compensation algorithm used to convert the readings to those which would be observed at 25 C also influences the accuracy of the reported value. TOC600 Analyzer SOP Number: TOC600-6

52 Page 52 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer Validation of the calibration of conductivity instrumentation may be accomplished several ways. Instruments which allow the cell to be disconnected from the measurement device may be verified by substituting NIST traceable resistors in place of the cell. The USP requirements specify that the instrument accuracy must be at least ±0.1 µs/cm. In addition, the USP requirement states that the cell constant of the measurement cell must be known to ±2%. Cell constants may be determined by measurements of solutions of known specific conductance. Another method of verifying the cell constant is to compare its measured conductivity with that obtained from a certified cell. This may be accomplished by comparing the readings obtained by the instrument s measurement cell to those of a cell with a known constant. Both cell readings are taken on an atmosphere equilibrated high-purity water sample. 4.5 USP Conductivity Test Limits 5 Total Organic Carbon (TOC) The USP has a three-stage test for the conductivity measurement limit. Stages 1 and 2 are preliminary fail-safe tests. If the test conditions and conductivity limits are met at either of these stages, it is impossible to fail the critical third stage of the method. Only in the event of failure at the final test stage is the sample judged non-compliant with the requirements of the USP conductivity test. Stage 1 is the only test condition that can be performed online. Refer to USP document <645> Water Conductivity for the test conditions and specifications of Stages 2 and 3. The water sample meets the conductivity test requirements for Stage 1 if the conductivity is no greater than 1.3 µs/cm at 25 C. For the on-line conductivity measurement of hot water to comply with this test requirement, the instrument s temperature compensation function must be disabled. This confirmation may be achieved by comparing the instrument s temperature-corrected conductivity reading to that of a 25 C adjusted side-stream measurement using a separate calibrated instrument. The temperature-corrected reading may be used if it is not less than the 25 C reading. Total carbon (TC) is the sum of the inorganic carbon (IC), which may be present from dissolved carbon dioxide (CO 2 ), and bicarbonate ions, as well as the Total Organic Carbon (TOC) present due to any organic molecules dissolved in the water. The TOC in water is the sum of the purgeable organic carbon (POC) and the non-purgeable organic carbon (NPOC). Anatel TOC600 Analyzer SOP Number: TOC600-6

53 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer Page 53 Analytical technologies utilized to measure TOC share the objective of completely oxidizing any organic molecules dissolved in a water sample to carbon dioxide, measuring the resultant CO 2 level and then expressing this response as carbon concentration. Several commercialized instrumentation techniques meet the USP criteria for sensitivity, specificity, selectivity, precision, accuracy, and validation. Included in these techniques are combustion oxidization, heated persulfate oxidization, ultraviolet oxidation, and ultraviolet/persulfate oxidation. Most instrumentation measures the liberated CO 2 by infrared analysis of a carrier gas stream which has purged the CO 2 from the water. Conductivity measurements of liberated CO 2 dissolved in high-purity water are highly sensitive and used for quantitation. The carbon content of an organic molecule is calculated by multiplying the number of carbon atoms in the molecule by the molecular weight of carbon (12.01 g/mole) and dividing the product by the gram molecular weight of the molecule: Carbon Content = number of carbon atoms molecular weight (g) 5.1 TOC Measurement The TOC analytical technique must discriminate between the inorganic carbon and the organic carbon in the water sample. Two general approaches are employed to measure TOC. One determines TOC by subtracting the measured IC from the measured TC: TOC = TC IC The other approach purges the IC from the sample before any carbon measurement is performed. However, this IC purge may also remove some (or all) of any volatile organic molecules present in the sample. These purgeable organics can be trapped and quantified as POC. The remaining organic matter in the sample is then quantitated as NPOC. Using this approach, TOC is the sum of the POC and the NPOC: TOC = POC + NPOC Based on a study of water sources from a variety of pharmaceutical manufactures, the PhRMA Water Quality Committee has determined that the amount of POC in pharmaceutical waters is negligible and can be discounted. Thus, for pharmaceutical waters, the proposed USP revision accepts NPOC as the equivalent to TOC. 5.2 Units TOC is present in high-purity water in very small amounts. TOC levels of less than 250 µg/l for PW and 50 µg/l for WFI are the norm in well controlled pharmaceutical water systems. For these high-purity water TOC levels, the µg/l units typically are expressed as parts per billion (ppb). TOC600 Analyzer SOP Number: TOC600-6

54 Page 54 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer 5.3 Suitability of the Measurement Device Since a variety of analytical techniques may be used to determine the TOC level in high-purity water, the USP has provided guidelines on how to qualify the technology. The TOC test method can be performed either as an online or offline laboratory procedure using a calibrated instrument. No specific calibration procedure is mandated, testing normally being based on the instrument manufacturer s recommendations or requirements. Secondly, the suitability of the measuring device must be demonstrated periodically. This is done by analyzing a 500 ppb system suitability solution (in the form of 1,4-benzoquinone) to challenge the instrument s ability to analyze difficult-to-oxidize organic molecules. The result of this measurement is compared to the measured result of a 500 ppb Sucrose Standard. Both values are corrected for the TOC level present in the water used to prepare the solutions. 5.4 USP Test Limits The response efficiency (RE) calculated by: Where: ( R SS R W ) R E = ( ) 100 R S R SS = Average TOC response for three measurements of the 1,4-benzoquinone System Suitability solution in ppb. R W = Average TOC response for three measurements of Background Water used in the preparation of the Sucrose Standard and the 1,4-benzoquinone System Suitability solution in ppb. R S = Average TOC response for three measurements of the Sucrose Standard solution in ppb. R E = Response efficiency of the TOC600 Analyzer. R W 6 TOC600 Instrumentation must be not less than 85% or not more than 115% in order for the measuring device to be considered suitable (or acceptable) to qualify for use in PW and WFI installations. High-purity water containing not more than 500 ppb TOC meets the USP requirements for Total Organic Carbon. The instrumentation may be used as a limit test with the sample water meeting the USP requirement if it measures not more than the 500 ppb corrected sucrose standard instrument, or limit response. The measurement chamber of the Anatel TOC600 Analyzer consists of a high sensitivity conductivity cell containing titanium electrodes, a high energy 185 nm UV lamp separated from the conductivity cell by a UV transparent window, a temperature element within the cell, and a valve at the exit port of the cell. Anatel TOC600 Analyzer SOP Number: TOC600-6

55 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer Page 55 Fig 1 : The Anatel TOC600 Analyzer Unlike other on-line, high-purity water TOC analyzers, the Anatel TOC600 requires no reagents or carrier gases to determine the TOC content of the water sample. Volatile compounds are not lost during sampling handling and the sample s oxidation time is monitored rather than fixed to ensure complete oxidization of all organic molecules present. The operating range of the instrument is from 1 ppb to 1000 ppb TOC. 6.1 Principle of Operation A side stream from the process water system flows through the measurement cell when the sample valve is open. A water sample is then isolated in the analysis cell by closing the sample valve. The initial conductivity and temperature of the water are measured in order to establish a reference conductivity value, compensated to 25 C. Energy from a 185 nm mercury vapor lamp reacts photocatalytically with the titanium dioxide (TiO 2 ) coating on the titanium electrodes to produce hydroxyl radicals ( OH) which are a strong and efficient oxidizing agent. The organics present in the water sample are oxidized to CO 2, which dissolves in the water to form carbonic acid and subsequently dissociates as H + and HCO 3 ions. The presence of these ions increases the conductivity of the water while a sophisticated set of algorithms continuously monitors this conductivity change until oxidation is complete. The difference between the initial and the endpoint conductivity, compensated to 25 C, is used to determine the TOC in the water sample. The chemistry of this process is described as: Organics(aq) + OH CO 2 (aq) + H 2 O CO 2 (aq) H 2 CO 3 H + + HCO 3- TOC600 Analyzer SOP Number: TOC600-6

56 Page 56 Training on the Principles, Operation and Use of the Anatel TOC600 Analyzer 6.2 Sampling System The purpose of the sampling system is to provide an appropriate side stream of the process water to the Analyzer. The sampling system must deliver water at a temperature between 5 C and 95 C, restrict the inlet pressure to less than 100 psig, and provide a flow rate of at least 60 ml/min to the Analyzer. In pharmaceutical applications, this side stream must not be returned to the process water system. All materials that contact the stream must be constructed of 316 stainless steel, PFA Teflon or other suitable inert material. Fig 2 : TOC600 Sampling System 6.3 Instrument Configuration The minimum Anatel TOC600 Analyzer combines a Controller and a Sensor unit. Multiple Controllers and Sensors may be linked together via a proprietary local area network (A-Net) to furnish a wide variety of potential system configurations. 1) C80 Controller The C80 Controller serves as a control/display device for the TOC600 measurement system. A 4-line by 16-character display presents information. Function and edit keys provide the ability to display and modify the various parameters which control the Sensor s operation. 2) TOC600 Analyzer The TOC600 Sensor is the basic analysis device. A 1-line by 16- character display reports current TOC values in ppb. Operation parameters for the Sensor are established through a C80 Controller. Anatel TOC600 Analyzer SOP Number: TOC600-6