I had several really bad experiences lately with generic drugs whose bio-equivalency was explained to me by FDA means that "the generic drugs dissolve and absorb the same way and the same place as the brand name." I find this not to be the case. Often times generic drugs come without film coating and with cut line in the middle, indicating that it will dissolve in the stomach. For the same drug the brand name may come with a film coating and no cut line indicating that it dissolves in the intestines. Given the metabolic pathways, where the drug dissolves affects how it absorbs and where. Given that the active ingredients are the same, if a generic drug does not work the same way, can we say that the inactive ingredients have modified the drug to be a different drug? And if so, how can one address this in the US?
Hi Angela,
The bioequivalence is based in pharmacokinetic profiles (in vivo plasma-concentration/time curve) of the active moiety only (enantiomers, or metabolites when applied), that mean than plasma concentration are comparable across time, enough to establish equivalence under the requirements of regulatory authorities (rate test/reference within 80-125 acceptance interval). Previously to in vivo testing, the pharmaceutical form has to prove in vitro a sort of equivalence (similarity of dissolution profiles).
For immediate release formulation and for modified release formulation requirements are different; for immediate release often a Bioequivalence study in fasting state is enough, but for modified release at least 2 studies are needed fed and fasting state; that means that the bioequivalence has to be prove even in interaction with food, and in some cases for several dose strengh.
A film coat or not having a cut line isn’t necessary a sign of modified release formulation, several tablets who has film coats or not have a cut line can be dissolve in the stomach (some film coats are not gastro resistant or enteric, they are used also to cover the flavor of the drug product).
Some excipients (inactive ingredients) with some moieties are known to be incompatible, and both developer and regulatory authorities know that, in some cases developer are asked to do specific studies to demonstrate that his specific formulation (with specific inactive ingredients and moiety) has no incompatibilities.
What kind of bad experiences are you having lately? Less effectiveness, safety issues, are they related with a specific generic company? Or with a specific therapeutic group? Is this happening compared with a specific branded drug? How your patients fell about changing to generic drugs (if it’s the case)? Subjective issues tend to be relevant depending on the pathology.
Sorry but I can answer you your last question as I’m in Europe. I hope you find helpful this information
best wishes
Juan Manuel
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