Bioequivalence and Bioavailability Forum

Background information:
We are working on designing a multiple-dose steady state Pharmacokinetic (PK) Bioequivalence (BE) study of an Immediate Release (IR) Solid Oral Dosage form on cancer patients for EMA submission. We are exploring alternate study design due to the inherent challenges related to the recruitment and retention of cancer patients in PK BE study and have following questions.

Question: To address the challenges related to retention of cancer patients in PK BE study, we want to plan 2-period full replicate design. Will the EMA accept this approach for Immediate Release (IR) formulation?

As per EMA Guideline on the pharmacokinetic and clinical evaluation of modified release dosage form “Calculation of the intra-subject variability in multiple dose studies can be based on two consecutive administrations of the same product after reaching steady state.”

So, based on our interpretation this will be TTRR or RRTT design.

As per the published EMA Public Assessment Report (EPARs), there are few products approved by EMA using this approach such as Bupropion and Felodipine modified release formulations.

We want to know if EMA will accept us taking this approach for Immediate release formulation as this approach is mentioned in modified release guidance and the 2 examples which we could find were also modified release formulations.