White Paper

Refinement and Performance Testing of the Spreadsheet for Automated Calculation of Method VDmax Values

12/7/16

John B. Kowalski, Ph.D. Independent Consultant of Sterigenics/SteriPro President & Principal Consultant microGAMMA, LLC

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Introduction In a previous White Paper (1), a spreadsheet-based method was described to calculate the four VDmax values (SIP=1.0 Verification Dose, SIP Verification Dose, SIP Dose Reduction Factor, and Dose Augmentation Value) for a given input average bioburden, sterility assurance level (SAL), and minimum sterilization dose. The purpose of this document is to describe enhancements to the spreadsheet itself as well as give the results of a set of performance tests that were performed on the spreadsheet. Spreadsheet Enhancements The following enhancements have been introduced into the VDmax Values Calculation Spreadsheet (compare Figures 1 and 2): • The footprint has been made smaller by removing the test case and other extraneous

information.

• A cell has been added that documents the time and date the calculation was made.

• A cell has been added that documents the path and the file name of the spreadsheet.

• To ensure an acceptable value is readily entered in the five input cells, data validation has been added. When an input cell is selected, a pop-up appears that gives information on the range of acceptable values. The pop-up for the Minimum Sterilization Dose cell directs the user to additional guidance. See Figure 3.

• In the event an unacceptable value is entered, an additional pop-up appears indicating an error condition exists. See Figures 4 to 8.

• The ability to choose the use of 10, 30, or 90 product items for irradiation in the verification dose experiment has been added. The output VDmax values are automatically reflected the number of product items input.

Spreadsheet Performance Testing

The purpose of this testing was to "exercise" the spreadsheet to document that the intended output was observed for the test input values. • If the average bioburden obtained in a sterilization dose establishment is not found on a

conventional existing look-up table, falling between two tabulated values, the standard instructs the practitioner to use the closest tabulated average bioburden greater than the calculated average bioburden. Figure 9 shows the entry of an average bioburden of 502 and the automatic conversion by the spreadsheet to the closest greater value, 525. Figure 9 also shows a message in the "SIP VDmax Verification Dose" output cell; an SIP=1.0 has been input and therefore no SIP<1.0 value is output ("NA" message instead).

• Figure 10 shows the input of an SIP=0.5 into the base case (Figure 2) and the corresponding reduction of the verification dose. Because an SIP<1.0 was input, an "NA" message appears in the output cell for the SIP=1.0 Verification Dose.

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• Figure 11 shows the messages in the SIP-related output cells in the case where the input average bioburden is <1 and therefore use of an SIP is not permitted.

• Figure 12 shows the messages in the output cells when an SIP<1.0 is input along with an average bioburden <1, a combination not permitted. In this situation, no verification dose is calculated.

• Because average bioburden, SAL, and minimum sterilization dose are interrelated, it is possible to enter a minimum sterilization dose that is too low to attain the input SAL for the input average bioburden. The spreadsheet automatically calculates the minimum dose for the input average bioburden and SAL and then outputs the message shown in Figure 13 when the input minimum sterilization dose is too low.

• Figures 14 and 15 show examples of input values of 30 or 90 product items for the verification dose experiment. Compared to the base case in Figure 2, higher verification dose values are observed along with increases in the SIP Dose Reduction Factor and the Dose Augmentation Value. This increase in the output values is expected at higher average bioburden and the output values are correct.

• Figures 16 to 18 show examples of the input of 10, 30, or 90 product items for the verification dose experiment at a relatively low average bioburden value. In this case, use of 30 or 90 product items for the verification dose experiment, compared to 10 product items, leads to an increase in the verification dose only. This outcome is again expected and correct.

Conclusions The VDmax Value Calculation Spreadsheet described in this White Paper has been incrementally improved compared to the version initially developed and has "passed" the performance testing conducted thus far. This spreadsheet-based approach to calculation of Method VDmax values remains a work in progress and its final embodiment in the US will be defined by the AAMI Radiation Sterilization Working Group - ST/WG 02. 1. Development of a Spreadsheet for Automated Calculation of Method VDmax Verification

Dose, SIP Dose Reduction Factor, and Dose Augmentation Values. 11/14/16 http://www.sterigenics.com/docs/VDmax_Values_Calculator_White_Paper_111416.pdf

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Figure 1. Previously published screenshot of the VDmax Value Calculation spreadsheet.

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Figure 2. Current spreadsheet revision showing the performance testing base case: 1000 bioburden, 10-6 SAL, 25-kGy minimum dose, 10 product items for the verification dose experiment.

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Figure 3. Screenshot of data validation pop-ups when an input cell is selected.

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Figure 4. Attempt to enter unacceptable bioburden value (2,000,000).

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Figure 5. Attempt to enter unacceptable SAL value (10-5.7).

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Figure 6. Attempt to enter an unacceptable minimum sterilization dose (50 kGy).

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Figure 7. Attempt to enter an unacceptable SIP value (2.0).

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Figure 8. Attempt to enter un unacceptable number of product items for the verification dose experiment (35).

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Figure 9. Example of an input average bioburden value not tabulated in previous look-up tables showing automatic conversion to the next highest tabulated value (502 to 525).

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Figure 10. Example of entry of valid SIP value (bioburden >1, SIP = 0.5).

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Figure 11. Example of SIP-related values not output due to bioburden <1 (0.9).

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Figure 12. Example of entering an SIP value <1.0 when not allowed due to the average

bioburden entry is <1.0 (bioburden 0.9, SIP=0.5).

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Figure 13. Example of entering a sterilization dose too low for the entered bioburden and SAL

values (22 kGy, 25 kGy minimum required).

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Figure 14. Example of entering 30 product items for irradiation in the verification dose

experiment.

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Figure 15. Example of entering 90 product items for irradiation in the verification dose

experiment.

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Figure 16. Example of calculations for an average bioburden of 50 and 10 product items for

irradiation in the verification dose experiment.

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Figure 17. Example of calculations for an average bioburden of 50 and 30 product items for

irradiation in the verification dose experiment.

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Figure 18. Example of calculations for an average bioburden of 50 and 90 product items for

irradiation in the verification dose experiment.