Bioequivalence and Bioavailability Forum

Hello

Up to my know how proportional similarity could be define in one of two ways for FDA:

(1)all active and inactive ingredients are in exactly the same proportion (percentage) between different strengths: in all strength the percentage of API and inactive ingredients are similar (mass are different between strength but percentage remains identical): for example if a single bulk of granulate is existing the mass is increased proportionally to the strength for each strength;
(2)for high-potency drug substances (where the amount of active drug substance in the dosage form is relatively low) an additional option is existing, the total weight of the dosage form should remain nearly the same for all strengths (for example for FDA within ± 10 % of the total weight of the biostudy strength), the same inactive ingredients should be used for all strengths, and the change in any strength is obtained by altering the amount of the active ingredients and possibly one or more of the inactive ingredients. For example mass of formulation is similar between all strengths (for example when API is decrease lactose is increased to keep mass identical).

for FDA specifically, for Abbreviated New Drug Applications (ANDAs) for generic drug products if active and inactive ingredients are not compositionally proportional between different strengths, the strengths can be considered proportionally similar with adequate justification (such as in vivo dosage form proportionality studies that demonstrate equivalent BA).

Rules for Europe are close except for(2) where mass must be identical or only decrease by the amount of API and only one filler could be used to compensate it and API limit is fixed at 5% for all strengths.

Hope that could help you

best regards,

JM