Bioequivalence and Bioavailability Forum

Thank you ElMaestro.

❝ From a GCP perspective you are on thin ice. You dosed drug to humans and the entire thing was futile because you hadn't done your homework. I am aware that some companies really conduct these studies when stability has not been investigated or proven and often with success and the partial benefit from hindsight but yours is an example which shows it can be a bad idea.

The molecule showed no sign of degradation during method development and validation. Even during bioanalysis no difficulty was observed until repeat analysis. Upon investigation it was observed that the molecule degraded, and LTM confirmed it.

❝ At this point I hope both you (sounds like you are at a CRO?) and your sponsor will stop up and think. What got you into that mess? How do you avoid getting into one such mess again?

❝ And then I hope you'll wait with the next study until you have come up with something concreet and useful.

To overcome the issue, we plan to re-develop and validate the method, and prove the stability for 80 days before re-conducting the study. Once we have proven stability and the molecule meets the bioequivalence criteria, we wish to submit it to FDA.

❝ For a person or company in your situation that is the wrong question to ask at this point.

My point is, how can we justify to FDA to re-do the study. Should there be a change in exhibit batch used for dosing, the study can be re-done without objection. But because now, the same exhibit batch will be used for dosing, how do we justify to the regulatory.

❝ Any IRBs and IECs reading this? How about making sure stability really has been proven before the next study is approved?

Yes, we will make sure that the method is robust before execution.

Regards
Ram