'Generic Equivalent': What Does That Really Mean?

Christina M. Sorenson, OD


October 02, 2017

In recent months, I have seen an increasing number of medication changes from a branded product to a generic drug: generic substitutions, change to generic at refill, insurance non-coverage for branded product, patient request for a generic medication, and a few other variations. I got to thinking about all of the generics, branded generics, authorized generics, and bioequivalent and biosimilar medications now available. What are all of these options, and what do they mean for patient care?

According to the US Food and Drug Administration (FDA), a generic drug is identical—or bioequivalent—to a brand-name drug in "dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use."[1] This statement seems straightforward enough. After all, how much different can a drug be if it meets the parameters of the FDA definition? In the United States, generic medications must be proved to be bioequivalent to gain approval.

The misconception that generic drug concentrations are somewhere between 80% and 125% of the branded product—a whopping 45% variance—persists.[2,3] In fact, bioequivalent drugs have the same rate and extent of drug absorption and are required to fall within 90% confidence intervals. (We could have a long discussion on the area under the curve [AUC] representing drug absorption and concentration within the 90% confidence interval, which reduces the variance of generics to the branded product, but I'm not a chemist or a pharmacist, nor inclined to be!) The consensus from the pharmaceutical professionals and the FDA is that differences in this confidence interval are not clinically significant.

If all of that is true, why do we see a difference in outcomes for some patients?

What we know is that generic medications may make use of different chemical versions of the medication, such as another salt, or use different excipients to stabilize the drug.[2] Each of these changes may lead to different absorption properties or even an adverse reaction. These types of medication challenges are unknown, however, as generic drugs do not undergo the rigorous clinical testing that the initial branded product does.

Additionally, pharmacies may change which generic version they purchase to obtain the medications at the best price. We can almost expect different generic versions to be dispensed each time the prescription is refilled. With each "brand" change, we may find differing therapeutic outcomes. Moreover, drug confusion with packaging changes between generics and the branded product can lead to poor compliance or incorrect substitutions by the patient.

Branded generics are another option. A branded generic is the bioequivalent medication marketed under another company's brand name. Branded generics differ from authorized generics in ownership. An authorized generic is an exact copy of the brand-name version authorized by the original patent holder of the drug product. The brand company submits a New Drug Application (NDA) and markets the generic under a private label. It is identical to the branded product in appearance (shape, color, markings) and inactive ingredients.[4] You may see these medications called "pseudogenerics" or "ultragenerics."

Large-molecule medications made from living microorganisms of animal or plant cells are known as biosimilars, biogenerics, interchangeable biologic products, or simply biologics. These are not truly generic medications, as the generic term applies only to small-molecule medications that are bioequivalent. This group of medications is found to be "highly similar" to a bioequivalent medication.[5]

For ophthalmic topical forms, bioequivalence studies may be suboptimal in determining clinical effectivity. Ophthalmic topical medications are administered at the site of action and have no reliance on systemic absorption but merely local penetration to ocular tissues. Reviewing physiochemical properties, including pH, viscosity, and osmolarity/osmolality, might lead to clearer clinical standards and expectations.

Knowing these definitions help me understand where I might encounter drug therapy failure and provide me with a course of action to obtain the best outcomes for my patients.

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