Do you need to reduce the sterilisation parameter, e.g. time or temperature when doing validation or re-qualification of an SIP process, to show worst case? We test the process by temperature monitoring and using BI.
The SIP process is already overkill in my opinion. Set point is at 121.5deg for 20 minutes. Would reducing time and/or temperature means tampering with the program and makes your validaiton questionable?
A good reference for autoclave validation is PDA Technical Report #1 - Validation of Moist Heat Sterilization Processes.
From the section of Process Performance Qualification - “In order to assure consistent delivery of the minimum acceptable cycles, routine operational cycles generally include a safety margin through the use of higher temperatures and/or exposure times.”
To answer your question - Will your validation be acceptable if you execute at operating parameters? Yes. You will then have more risk if your process deviates from established specifications. It is recommended to validate outside of the intended operating range, but not necessary depending on the amount of risk you are willing to take.
As a part of validation if worst case is to be excercised it is not considered as tempering with parameter. Reason is that at this stage parameters are not freezed & can not be viewed as final validated CCP. During validation we always have liberty to challenge the CCP for desired results/acceptance criteria.
Generally, in steam or dry heat sterilization/depyrogenation cycle, we should challenge worst case with biological/endotoxin indicators.
Rgds
Ravi Dhanbhar
Thanks for all the replies. What about during routine re-qualifications? The parameters are already set in place. Should you do routine requalifications at reduced (worst case) parameters or routine production parameters?
For SIP, we use approximatley 2/3 of manufacturing SIP dwell time for PQ as well as revalidation as a worst-case to prove that the SIP cycle is effective. For example, if the manufacturing configuration (circuit) has 30 minutes of dwell time, the validation is performed with 20 minutes of dwell time (if 20 minutes then we do 15 minutes). The duration of dwell time depends on your F0 (lethality) acceptance criteria. If you are using the worst-case approach, you would have to make sure that you are getting enough kill (F0) to meet your acceptance criteria for lethality (F0). Since F0 depends on actual SIP temperature and time, you could perform a theoretical F0 using your temperature data (could be historical data) to make sure you are meeting the acceptance criteria if a worst-case (shorter time than manufacturing cycle) is used for validation. For example, if your acceptance criteria for F0 is 12 minutes, validation at 15 minutes should be enough at 121 deg-C or higher to achieve the required F0.
In such case if want to to reduce your SIP I think it should be covered in “Risk assessment study of tank”, then you can easily challenge your worst case conditions.