In carrying out its mission to ensure that generic drugs are "the same medicine" with "the same results" as the pioneer drugs they follow, the Food and Drug Administration rigidly applies a standard of what is called "bioequivalence." Measured in laboratories and in simple, small-scale human trials, a generic must deliver the same active ingredient to the bloodstream of patients in virtually the same amount at virtually the same rate as the pioneer drug.
The FDA considers "bioequivalence" a good surrogate for "therapeutic equivalence" -- the equal ability of two drug formulations to ease symptoms or cure disease. Physicians and pharmacologists say that for some copycat drugs, showing bioequivalence to the original is not proof enough that the "same medicine" will yield "the same results."
There are several potential flaws in the FDA's standards of comparison, drug experts say.
Generic drugs: An article in the Monday Health section about the FDA's standard of "bioequivalence" to generic drugs said that a comment by neuropsychiatrist Dr. Giuseppe Borgheini about bioequivalence was from a 2004 article in the journal Clinical Therapy. The article was actually published in a 2003 issue of Clinical Therapeutics. The same story incorrectly identified the brand name of the anti-seizure drug valproic acid as Felbatol. The correct brand name is Depakote. Also, the anti-seizure drug phenytoin was identified as Cerebyx. That's an injectable form, however; the drug is more commonly known as Dilantin.
Generic drugs: An article in the March 17 Health section about the FDA's standard of "bioequivalence" to generic drugs said that a comment by neuropsychiatrist Dr. Giuseppe Borgheini about bioequivalence was from a 2004 article in the journal Clinical Therapy. The article was actually published in a 2003 issue of Clinical Therapeutics. The same story incorrectly identified the brand name of the anti-seizure drug valproic acid as Felbatol. The correct brand name is Depakote. Also, the anti-seizure drug phenytoin was identified as Cerebyx. That's an injectable form, however; the drug is more commonly known as Dilantin.
First, the agency's tolerance for variance in the content and release of a drug's active ingredient -- the healing compound -- may be too broad.
Second, the FDA does not demand realistic trials of different formulations in large patient populations.
And third, by measuring a generic medication's ability to deliver a drug compound to the bloodstream, the FDA may be looking in the wrong place. Most drugs work their magic not in the blood but in organs, cells or tissue elsewhere.
In fact, a brand-name drug's generic counterpart is rarely an exact replica. Though the two share equal amounts of the same active ingredient, they generally look different. And those differences, say some pharmacologists, can result in small variations in how they work in patients.
A brand-name drug and its generic in most cases are formulated with different colorants, fillers and binding materials. Though all of those must come from an FDA-approved list of pharmaceutical ingredients, they are, in most cases, assembled differently in each manufacturer's product. One version of a drug might use lactose or sugar as an inactive ingredient; another might not. But incidental ingredients like these can affect the way patients dissolve and metabolize a drug's active ingredient -- faster or slower. And that, in turn, can result in variations in the two formulations' effects.
