As is typically the case with regulatory, this is no 1 short/correct answer, since there are several variables to consider - 2 APIs, strengths, fill sizes, stability requirements, risk analysis, etc. There is a presentation from the Spring 2015 REdI Conference that discusses this topic, and might explain it better. On the SBIAEvents site, you can download both the slides and a recording of the event. I think the one on Stability by Rajagopalan and Pantankar will really help. I would be more cautious/conservative with the sterile product (each batch of API into each fill size), and allow more flexibility/bracketing with solid orals.
I recently did a sterile injectable with 1 strength, 2 fill sizes. We made 6 batches (3 of each fill size) because each batch was dedicated to one fill size.
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Lisa Apolis
Regulatory Consultant
Alexandria VA
United States
Original Message:
Sent: 25-Aug-2016 16:40
From: Cynthia Katsempris
Subject: 2 discrete lots of API
Hi Lisa,
But what if you have 6 batches, 3 of each fill size for sterile injectables? or multiple strengths of tablets? Would each fill size/strength need to use 2 discrete lots of API?
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Cynthia Katsempris
Director, Regulatory Affairs
Three Bridges NJ
United States
Original Message:
Sent: 17-Aug-2016 08:12
From: Lisa Apolis
Subject: 2 discrete lots of API
Hi Cynthia,
My understanding is the Agency doesn't want you to use the same lot of API when preparing the 3 bulk exhibit batches, and it isn't related to the fill size of the DP. The goal is to show that different lots of API don't affect the DP. So you would use 1 lot of API for 1 DP batch (regardless of how it is filled), and a second API lot for the other 2 bulk DP batches. You could do 1, 1 and a mix for the 3 batches, or use 3 API lots if you want. If the different DP batches have different fill sizes, make sure your filling matrix will cover extremes for stability.
Hope this helps,
Lisa