Hi, Shelley -
As the previous respondents noted, I have not seen a hard and fast requirement for number of vials. However, the number of vials should be representative of your commercial process, and optimally should include the maximum batch size. If you cannot produce the maximum batch size, you will need a justification for why the reduced scale is representative, and may want to discuss with the relevant regulatory authorities.The two guidances below may help.
FDA: Process Validation: General Principles and Practices (2011)
EMA: Guideline on process validation for finished products - information and data to be provided in regulatory submissions (2016)
Best,
Cathy
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Catherine Anderson PhD, RAC
Senior Manager - Regulatory CMC
Hillsborough NC
United States
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Original Message:
Sent: 03-May-2018 09:38
From: Sarah Bakker
Subject: Process Qualification
Dear Shelley,
It is my understanding that you are required to run process validation/qualification at your largest intended batch size to demonstrate the process is robust, and that this would be critical for a sterile product. Note, that for submission purposes in the US, you do not need to have completed process validation at commercial batch size.
I believe that Victor is referring to the SUPAC guidance, which is for scale up post approval. If this is the guidance, the value of 10x is to establish post approval reporting category, and does not reflect the requirements for validation. It is also indicated in that guidance that "All scale-up changes should be properly validated", unfortunately, it does not indicate what properly means. If this is not the guidance being referenced, I am very intrigued to read the one in question.
With that said, my expertise does not lie in validation, and I am very interested to receive other members experience and advice on this topic.
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Sarah Bakker RAC
Regulatory Project Manager
Original Message:
Sent: 02-May-2018 08:28
From: Victor Mencarelli
Subject: Process Qualification
Hi Shelley.
I remember some years ago the FDA came out with something on the specifics around process validation. I seem to remember that it was more along the lines of what production size would be acceptable to consider "scale-up" but I don't remember the exact title any longer and I don't have a copy of the guidance in front of me currently. However, I recall that the key was that the validation runs could support up to a 10x increase in "normal production" meaning that if you plan is to run 80k sterile vials, your validation runs should not be less than 8k vials each.
I am not an expert in this area but I would think that would be at the outside of the statistically applicable lower limit in order to ensure that you have sufficient reliability, reproducibility, etc. when you move to your planned standard production levels. I might suggest looking at doing a bit more (upwards of 15-20k units) if you want to be on truly solid ground if you are ever questioned.
I look forward to any of our other process qualification experts who might be able to shed more light on this sort of question!
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Victor Mencarelli
Director Regulatory Affairs
United States
Original Message:
Sent: 01-May-2018 13:59
From: Xueling Shen
Subject: Process Qualification
Hi RAPS members,
I have a question regarding Process Qualification. Our commercial batch is 80,000 vials (sterile), how many vials should we run during PQ? Is there any guideline on this or just industry practice??
Much appreciate your response.
Regards,
Shelley