Generic vs Branded Psychiatric Medications: Is There a Difference?

Jane Lowers; Robert H. Howland, MD

Disclosures

April 25, 2012

In This Article

Defining Bioequivalence

Medscape: What does the FDA define as "bioequivalence"?

Dr. Howland: "Bioavailability" refers to the rate and extent of absorption of an active ingredient from a drug product so that it becomes available at its site of action. "Bioequivalence" means that the active ingredient of 2 drug products has the same rate and extent of absorption. When it acts on its target -- for example, a receptor in the brain -- the brand-name and the generic drug should deliver the same amount of active ingredient to the target site.

There are different ways of assessing bioavailability. The most common method is to conduct a pharmacokinetic study, in which the drugs are given orally and you measure how much of the active ingredient of the medication is actually absorbed and detectable in the bloodstream by collecting blood samples at different time points after administration.

In these types of studies, the 2 parameters that the FDA defines as important for evaluating bioequivalence are the rate of absorption and the extent of absorption. When you administer a drug and measure serum concentrations at 30 minutes, 45 minutes, 1 hour, 90 minutes, and so on, you can calculate what's called the "area under the curve" (AUC), which is the extent of absorption. The AUC represents a cumulative measure of drug concentration over time. The rate of absorption is defined by the FDA as the highest or maximum concentration that can be detected, referred to as "Cmax."

In bioequivalence studies, when you compare a brand-name drug with a proposed generic equivalent, the FDA has certain standards for determining whether the Cmax and AUC are similar enough to declare them bioequivalent. If a drug formulation differs in one or both parameters, the FDA would determine that this drug is not bioequivalent to the brand-name product.

Medscape: So that's how generic equivalents are tested. Do pharmaceutical alternative agents go through a separate process?

Dr. Howland: A drug that would be labeled as a pharmaceutical alternative could still be approved by the FDA on the basis of bioequivalence data, but it really depends on the product and how it's intended to be used. In some cases, additional efficacy and safety studies might be conducted along with bioequivalence studies.

In the past, before a generic drug could be approved, it also had to go through the same clinical testing for efficacy and safety as for an innovator product. In 1984, the Drug Price Competition and Patent Term Restoration Act, known as the "Hatch-Waxman Act," changed the definition of a generic drug and how it would be approved.

Before 1984, typically a generic drug would have to go through the same type of randomized trials to show efficacy, tolerability, and safety. On the basis of the notion that a drug containing the same active ingredient (if it's absorbed in the same way and has the same bioavailability as a brand-name product) is very likely to be therapeutically equivalent -- meaning that it's likely to be as efficacious and have the same safety and tolerability profile as the brand-name product -- the 1984 Act did away with the need to conduct additional effectiveness studies and greatly expedited the development of generic products.

So now, if a company wants to manufacture a generic drug, they conduct bioequivalence studies and submit those data to the FDA. A therapeutic equivalent drug -- a generic drug -- is something that can be substituted freely by a pharmacist in accordance with state laws. Pharmaceutical alternative drugs, on the other hand, can't be substituted for a brand-name product except by prescription.

For example, there are various brand-name and generic formulations of the antidepressant bupropion hydrochloride. There's Wellbutrin®, Wellbutrin SR®, and Wellbutrin XR®, but there's also a pharmaceutical alternative product called Aplenzin®, which is bupropion hydrobromide. A pharmacist could substitute a Wellbutrin generic for a prescription that's written as Wellbutrin, but if the prescription says "Wellbutrin SR," then the pharmacy can only substitute a generic sustained-release product, but could not substitute Aplenzin or one of the other release formulations. For certain drugs, it does become very complicated in terms of what is generic and can be freely substituted.

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