We are developing a topical ointment for US and Europe. Content Uniformity testing is required per USP <3>. After experiencing some high test results on stability due to what was believed to be possible API agglomeration, it was decided to increase the sample size from 0.5g to 5g. But now our clinical team is saying the sample size should reflect the minimum dose being studied in the clinical trials which in this case could be as low as 0.175g. While I agree this is ideal, is anyone aware of this being a requirement? Is this captured in any FDA guidance? We will ask our CMO for their opinion on how small of a sample size can be used with their method, but we are hesitant to reduce, especially to as low as 0.175g. We are thinking of proposing to FDA at our EOP2 meeting using a smaller sample size (something < 5g), but not as small as 0.175g. Any experience people have had or suggestions on approach with FDA are greatly appreciated. Than you.
Tom
Chicago