Rx Perspective
Stricter Standards for Generics?
Not likely soon. FDA says policy is based on our "best science."
BY LOUIS PILLA, CONTRIBUTING EDITOR

Prescribing generic drugs instead of brand-name or "pioneer" medications saves the healthcare system billions of dollars each year. But can you prescribe them with the same confidence you would the brand-name agents?

Unfortunately, that's not a question that lends itself to a "yes or no" answer. Richard Bensinger, M.D., spokesperson for the American Academy of Ophthalmology, says that he prescribes generics with the same confidence as brand-name drugs. He makes sure, however, to monitor his patients closely.

SOME NEW THINKING RECENTLY

But such substitutions may not always be safe and effective, according to Mark B. Abelson, M.D., associate clinical professor of ophthalmology at Harvard Medical School and senior clinical scientist at Schepens Eye Research Institute in Boston.

"It is true that relatively small changes in formulations can make significant effects on the safety and efficacy of ophthalmically administered drug products," says Wiley Chambers, M.D., deputy director of the FDA's Division of Anti-Inflammatory, Analgesic and Ophthalmic Drug Products. "So at least in recent years, particular attention has been paid to that."

Chambers agrees that generic ophthalmic drugs must be bioequivalent to their brand-name counterparts -- that is, the generic drug must deliver the same amount of active ingredients in the same time as the pioneer drug.

But a generic drug can be shown to be bioequivalent but not provide the same comfort for the patient, which can lead to noncompliance, says Abelson.

THE QUESTION OF EQUIVALENCE

All of this begs the question of equivalence. The FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the Orange Book, lists approved drug products that are bioequivalent, including new drugs, generics, and antibiotics. "Drug products," it says, "are considered to be therapeutic equivalents only if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling."

Unfortunately, as Abelson noted in a published report some years ago, the system isn't as straightforward for various ophthalmic preparations. Specifically, drugs approved before 1962 may be considered therapeutically equivalent if they're pharmaceutically equivalent.

In discussing whether ophthalmic generic and brand-name drugs are equivalent, Chambers distinguishes between solutions and suspensions, ointments, gels, and other formulations.

For solutions, which aren't subject to much variability, the FDA requires that original manufacturers remain within 10% of each active ingredient from batch to batch. Beginning in about 1992, the FDA adopted a policy of approving generic ophthalmic solutions if they contained all the same active and inactive ingredients within ±5% of the innovator's concentrations.

Given that 5% tolerance, "it is difficult to argue that there is any difference from the lot to lot manufacturing capability" of the drug's originator, according to Chambers. With that 5% window in place, a solution "on the face of it is considered to be bioequivalent."

But suspensions present a different story, where the manufacturing process and particle distribution size, for instance, can affect safety and efficacy. Since 1992, the FDA reviews clinical testing with a clinical endpoint to ensure that the generic formulation has the same efficacy as the brand-name drug.

"BEST SCIENCE"

Will the FDA put in place additional testing to ensure the equivalence of generic and brand-name drugs? Chambers notes that "the procedures in place now are based on the current best science. If the science changes, the requirements may also change."

Pilla is a freelance healthcare journalist based in Horsham, Pa.