Bioequivalence and Bioavailability Forum

Dear all,

Nice to be a member here. I am working at a BE center located in Thailand as pharmacist and some part as project coordinator. There are some issues rested from time to time because our company is quite new in this business.

I'd like to explain to you some situation. Any comment, suggestion and opinion are appreciate for more understanding of myself and co-workers.

Since the approved protocol was written something like "... After volunteers receive the test product with 250 ml. of water, they do not allow to lay down. Only sit or semi-reclining is allowed for two hours after drug administration....." There are no problem for all of previous study until this. At first period, one of our volunteer blacked out at the early time point (40 minutes after drug administration) of blood drawing schedule [for your information, Tmax of this study drug (from literature) is around 1.5 - 4 hrs]. The volunteer was still conscious but lied down for 3 hrs and insisted to continue the study. The vital sign was OK. No problem with blood pressure and the doctor came to investigate him immediately and confirmed that he was OK to continue. This volunteer can complete both period with no harm.

Here are the questions
1. Is this a major deviation in GCP point of view?
2. The study staffs knew that this is a protocol deviation. Are we make wrong decision to let this volunteer continued in second period? If the point concerned is not concern for GCP but for the drug concentration in plasma.
3. OK.... what was passed is passed. Now among our staffs are discussing about should we drop out this subject or not?

The QA with Mr.Statistician said : "Of course, we should drop him because this is protocol deviation. Why should we keep him?"

The clinical persons replied : "Hey!! both of you were not understand the clinical point of view. Just laying down is only minor deviation that may not effect absorption pattern. So it is OK to keep him."

The QA : "If you think there are little effect on absorption, why you write it down in the protocol............."

I think the dialogue above can clearly explain the situation. Please kindly give me some comment on this. Are our protocol to strict or it is OK? Is that true that just laying down is not a serious thing to be concern (just record it what happened and continue)?

4. If someone here had ever experienced this kind of this situation. Please share your story if you feel comfort.

May this is quite a silly topic but your helps will make me understand more.

Thanks in advance

YT