Bioequivalence and Bioavailability Forum

Dear Rahul

❝ Is matching a dissolution profile in multi pH media with innovator helpful

❝ to achieve the bioequivalence ?

If in vitro matching dissolution profiles would automatically lead to in vivo bioequivalence you would not need a BE study. Sometimes your formulation has a different dissolution profile but you are bioequivalent. According to CPMP/QWP/EWP/1401/98 Rev. 1: "In the event that the results of comparative in vitro dissolution of the biobatches do not reflect bioequivalence as demonstrated in vivo the latter prevails." So it is just a hint.

❝ With BCS class IV molecules with site specific absorption, what will be

❝ the criteria to achive the bioequivalence?

Good question. If you can answer this then you will become rich and famous.

❝ Are there any other tools other than dissolution study to identify the

❝ right test formulation to carry out the BE study?

You can try biorelevant media (FaSSIF/FeSSIF (fasted/fed state simulating intestinal fluid containing bile salt/lecithin) = media for mimicking the gastric environment), investigate the physicochemical characterisation of APIs, the influence of excipients, the influence of particle size, the influence of aggregation/wetting, sink conditions etc.

❝ What are the critical things which needs to be added in the study protocol

❝ to reduce the variability?

Standardization, standardization, standardization. Each period should be exactly be the same as the previous and the following. The treatments must be identical (only exception: study drug). It is not only a question of study protocol preparation but more a question of CRO staff performance.

❝ is partial replicate design helpful for class IV molecules?

It is helpful for highly variable drugs, not only for class IV molecules. You need a replicate design in order to widen the acceptance range for Cmax. I personally prefer the full replicate design since you get more T/R comparisons.

Regards
Dan