Roughly eight out of every 10 prescriptions filled in the United States come in the form of a generic, a pharmaceutical copy of a brand-name product that the Food and Drug Administration has pronounced to be demonstrably identical in all the ways that matter: purity, stability, absorption, and the amount of active ingredients.

But are all generics really created equal?

Not exactly. The FDA actually assigns letter grades when approving generics: An “A” means the drug is exactly the same as the once-patented drug it's mimicking, while a “B” might vary slightly in how it’s absorbed by the body. This information usually isn’t part of the drug’s literature; patients would have to ask the pharmacist for it. The agency also allows the generics' concentration of active ingredient in the bloodstream to be as much as 20 percent below or 25 percent above the brand's—a fairly wide window of variability.

Both A- and B-graded drugs are highly unlikely to cause any adverse events that wouldn’t otherwise be present with a brand name. But a key asterisk in the FDA’s protocol for approving generics is that they don’t require inactive ingredients to be identical. That means additives like certain dyes or fillers could be present in generics that might provoke an allergic reaction in users. And generics can sometimes use different time-release formulas than the brand-name drug, meaning the body may absorb the drug at a different rate. 

The FDA’s policies also mean a drug’s bioequivalence doesn’t actually have to be exactly equivalent: When drug companies lose exclusivity to manufacturing, they release the drug’s recipe, but not how to make it. That’s left for the generic suppliers to figure out. And they don't always get it right.

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In 2012, a generic of the antidepressant Wellbutrin was found to be therapeutically inferior to the brand, which led to the FDA initiating testing of generic drugs made overseas for impurities. And in 2009, the FDA admitted that some drugs have a thin margin of error, such as medications for thyroid conditions or blood pressure issues. For those drug categories, some patients and doctors insist on a brand name for better reliability.  

Should you be apprehensive of generics? For the most part, no: They’re cheaper than brand names and work just as well the vast majority of the time. But if you’ve recently switched from a brand to a generic and had unexpected results, you might want to check and see how the drug was rated, if the inactive ingredients are different, or if the generic is being sourced by a new supplier. If a drug has a small therapeutic dosage window, make sure the generic isn’t going too far under or over it: The American Heart Association, among other groups, reminds caregivers to carefully monitor switches to generics for this reason.

Small differences in the eyes of the FDA might, in theory, mean bigger differences when it comes to how your body reacts, especially if you’re receiving slightly more or less of a drug than you’re used to. For all of these reasons, finding that a generic doesn't work as well as the original may not be just your imagination. If this is the case, your physician can write “Dispense as Written” on your prescription to make sure you're given no substitutes.