What explains why some generic medications are less effective, biochemically speaking? Is it (combination of) binding material, protein folding, presence of isomers, or something else?

Medications that bind receptors have varying effectiveness, like estrogen versus phytoestrogens because of their folding conformation. These are likely to need smart chemical engineers to design a process to make the right isomers or whatnot.

But there's also medications like simethicone, better known as Gas-x which is a surfactant that decreases surface tension of gas bubbles so they diffuse easier. Would these be more likely to be identical to name brand?