Bioequivalence and Bioavailability Forum

Dear all,

According to section 4.1.1, first paragraph, of the EMA guideline on bioequivalence, 'The study should be designed in such a way that the formulation effect can be distinguished from other effects'.
Moreover, in section 4.1.8, subsection ‘Subject accountability’, second paragraph, of the same guideline, it is stipulated that ‘It is not acceptable to have a protocol which specifies that ‘spare’ subjects will be included in the analysis only if needed as replacements for other subjects who have been excluded.’
Does this imply that the study should be conducted simultaneously in the whole study population? If so, can you please cite the source where this requirement is provided explicitly, perhaps in the scientific guidelines of other regulatory bodies.
I would be very thankful for providing any response.

Kind regards,
Peregrin