Hi!
I am having a few questions regarding process simulation study.
Please give me answers.
1.
Is it necessary to simulate full operation time during the study?
Example my regular operation in a equipment takes 48 hrs. Is it
necessary to simulate /Keep media in the equipment for 48 hrs?
2. Is
it necessary to simulate full batch size? Example my Batch size is about
180 kg, Is it necessary to use 180 kg of media during the study?
3. Whether an unqualified personnel is allowed to enter in aseptic/critical area during the study?
Waiting for responses.
Thanks & Regards
S.Gurusamy
- Is it necessary to simulate full operation time during the study?
Example my regular operation in a equipment takes 48 hrs. Is it
necessary to simulate /Keep media in the equipment for 48 hrs?
- Is it necessary to simulate full batch size? Example my Batch size is about
180 kg, Is it necessary to use 180 kg of media during the study?
- Whether an unqualified personnel is allowed to enter in aseptic/critical area during the study?
1). Yes. This should match the actual processing time.
2). Yes, again this should represent the actual batch.
For both of the above, you could cover a range, in which case you would do max and min and target.
3). I wouldn’t recommend it.
The duration of the fill is a critical aspect of an approved run. If your run is 48 hours, then you media fill (simulation) must also be 48 hours at a minimum. Most companies will go even longer during media fills just to be sure. Otherwise an upset in your process can cause the batch to be discarded, or cause additional testing (done under an incident/exception/CAPA/deviation)
The volume/mass of the media isn’t required It is the number of units which is critical. You need to fill each unit so that there is enough to coat the walls of the vial, when swirled. But you have to leave enough air in the vials so as to provide oxygen needed to support microbial growth. So typically about 1/3 to 1/2 full is sufficient.
Don’t put an unqualified person in the area. Either qualify them and bring them in, or else rely on the cameras (if it is an executive/manager type person who just wants to watch) - most audits now require cameras so as to watch the process since access is limited.
Also, a media fill has a lot of details like the ones I’ve answered above. Make sure there is a definite goal/plan and description of your process, the interventions, your people, your filling speed, your duration, etc. Please feel free to ask additional questions online or through private message.
I am in an Sterile Bulk API production unit, Our process includes
preparation of Sterile API from a Non-Sterile API through Filtration and
recrystallization.
After sterile filtration, product is handled aseptically throughout the
process. In some cases in closed equipments such as Crystallizer, ANFD,
Filling machines. Final API product is aseptically unloaded from Filling
machine into Primary packing containers.
In Crystallizer our processing is about 6 to 9 hrs, In ANFD it is around
10-40 Hrs. My question is to get clarity on the operation involved in the
closed equipments.
Once the sterile material is in hermetically closed equipment is it
necessary to do hold time for the entire operation duration during
mediafill?
Aseptic handling of the product is done during the unloading of product in
Filling machines.
Kindly clarify
Thanks in advance
Yes. The API can degrade over time and temperature via a splitting of the molecule (de-esterification). Microbes may have nothing to do with hold time. You basically have to ‘prove’ your contention that the drug product is not harmed via a prolonged hold time.
Are you challenging the sterile hold of the product? A hold time would show that the filtration was adequate, and that it was in fact hermetically sealed. I’m not sure about this, but there might be another way to show that your process is in fact closed and sterile.