Bioequivalence and Bioavailability Forum

dear all,
what is the upper limit for accepted blood volume that can be withdrawn for a BE study in healthy human beings.
i would like to know the regulators/guidelines specifications.
also what is the limit an IRB/IEC can approve.

in general for a typical bio study, the blood wont exceed more than 400 mL, however there are atypical studies in which we need to design a four period replicate, containing double or triple analytes to be measured and add to this sponsor seeks double aliquots of plasma samples. under such conditions the total volume of blood loss exceeds 700 mL.
so my question is how can we perform the study with such mammoth blood draw.
also getting the IRB approval is very difficult.

plz clarify

thanks!!