necessity of retention samples for pilot BE study [Regulatives / Guidelines]

posted by Shuanghe  – Spain, 2019-11-25 18:42  – Posting: # 20870
Views: 223

Thanks, ElMaestro!

» It is not clear, given exactly the wording quoted by Ohlbe what status to give to the pilot. On one hand the pilot does not give pivotall proof of BE, on the other hand it does seem required when you read the PSG.

In this specific case, I would ship retention samples for both pilot and pivotal BE.

To generalize it a little bit, I probably would send retention samples for pilot BE for all topic dermatologic corticosteroids for which vasoconstrictor study is required because, as mentioned in the guidance for "Topical Dermatological Corticosteroids: In Vivo Bioequivalence", the objective of the pilot for this type of the study is to "define the appropriate parameters for the pivotal study" due to the variable dose duration-response characteristics. Since the design of the pivotal BE depend highly on the pilot study, it make sense to treat the pilot specially (don't know how to put it in words but you get what I meant to say).

For other drugs, pilot BE will help you to fine tune the blood sampling, check/validate the bioanalytical method etc. So it helps you to make decisions (e.g., go to pivotal with the same formulation or modify the formulation), but in general, it won't define the parameters of the pivotal BE as mentioned in the topic corticosteroids guidance.

» One can of course go into the semantics and discussion the practical meaning of "required" and "recommended" etc.

No, I won't go there. :-D

» To me, if it is in a FDA BE guidance (PSG or not, draft or not) to do X, Y and Z, then I do X, Y and Z without shortcuts unless I have a tremendously good reason from FDA not do to do so.

Completely agree. The problem is that, in this case, there's no clear requirement. We don't know if there's X/Y/Z.

» I'd do full retention, switch CRO if necessary in the absence of a controlled correspondence or FDA communication to the opposite.

I'm sure I can talk with CRO and push a bit more, maybe they'll agree with the amount. Change CRO is also an option.

However, I would like to know the general consensus on this, if there's any, so I can improve the internal procedure (e.g. our SOP) with this regard.

» In perspective: Is the Beclo/Calcip guidance the first one mentioning the need (or whatever it is) for a pilot?

No, I don't think so. There are quite a lot PSG require pilot, almost all are for vasoconstrictor study, e.g., Clobetasol propionate, Fluticasone propionate , etc.

All the best,
Shuanghe

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