Dear All,

Please find below the calculation by which I am running the autoclave validation. My approach is half cycle method and double the cycle time for routine validation. Now for SAL value calculation what will I do. What formula I use. Mention that BI population is 1.2 x 106 and I have no facility to find out population after autoclave.

Overkill Cycle Approach: For achieving the over kill cycle half cycle method will be followed. Through this process 6 log reduction of Biological indicator (BI) will be documented and during production cycle run time will be double to ensure the overkill approach i.e. 12 log reduction.

Consideration of MPE: Validation temperature will be set considering the 1°C MPE of the autoclave internal sensors.

Calculation of validation set temperature and time for half cycle:

What How

Calculation for 6 log reduction Calculate the dwell time at 121°C

```
Temperature compensate the dwell time L121 = 10 (Tset-121° C) / Z
ttest = tK / L 121.1
Set the Validation cycle time tVC ≈ ttest
```

Method

Calculation of sterilization time at 123 0C considering MPE 1C for minimum 6 log reduction (half cycle approach)

```
What How Result (minutes)
```

Calculate the dwell time at 121°C 2.0 * {2+ log10(106)} 16

Temperature compensate the dwell time L121=10(123-121)/10 1.58

Ttest=16/1.58 10.13

Set the Validation cycle time tVC ≈ ttest 10.13 ≈ 10

Justification of run time 10 minutes: Run time will be 10 minutes as worst case validation. If it can be proved that running with 10 minutes (instead of 10.13 minute), minimum 6 log reduction can be achieved, then for 12 log reduction cycle total run time will be 20 minutes. But during production cycle real run time will be 22 minutes i.e. more than the requirements of overkill cycle run time which is 20 minutes. So, the validation is designed as worst case validation considering the time and temperature.

Run time and temperature for Production Cycle: For production cycle 1°C MPE will be added with the validation sterilization set temperature and to achieve this set temperature 1°C heating temperature will also be added with the validation heating temperature & Jacket Temperature i.e. production set sterilization temperature will be 124°C and run time will be (20 minutes + 2 minutes) i.e. 22 minutes for achieving the over kill.

Acceptance criteria for Production Cycle:

Run Time: Cycle run time should complete 22 minutes.

Temperature: During the sterilization period temperature should be 122 – 126 (set temperature is 1230°C) and at a certain time point, temperature for all sensors should not differ from another by more than 2°C.

Justification for Acceptance criteria of lethality value for Half cycle and Full cycle (Production Cycle) at steady state:

(A) As per validation Protocol:

At 121.1°C, required lethality For Overkill = D X 6 minutes

The BI that is to be used in this Execution has a D-value of 2 minutes

The required lethality for overkill = 2 X 6 minutes = 12 minutes

Considering MPE as 0.5 °C = 121.1°C + 0.5 °C = 121.6°C

At 121.6°C, Lethality Rate = [L121.6 = 10 (Tset-121 ° C) / Z],

= [L121.6 = 10 (121.6-121 ° C) / 10], = 1.15

The required lethality for overkill = Lethality Rate X 12 minutes = 1.15 X 12 minutes = 13.8 minutes

So, for half cycle acceptance criteria for lethality value should be ≥13.8 minutes.

For Production Cycle: As the acceptance criteria for half cycle is ≥13.8 minutes, so minimum lethality value for all sensors should be ≥ 27.6 minutes for full cycle (Production Cycle).