Bioequivalence: Definition, Testing, FDA Approval Standards

What Is Bioequivalence?

Bioequivalence is the biochemical similarity of two (or more) drugs that share the same active ingredient(s) and desired outcome(s) for patients. Pharmacokinetic studies must be done to determine whether a commercially available brand and a potential generic version share core attributes. Bioequivalence or pharmaceutical equivalence must be present showing that the two drugs release the active ingredient into the bloodstream at the same amount, the same rate, and have the same quality.

The U.S. Food and Drug Administration (FDA) regulates and approves drugs to ensure they meet the FDA's bioequivalence standards. When assessing how well a generic drug works, scientists evaluate its bioequivalence to the name-brand version.

Understanding Bioequivalence

Bioequivalence, according to the FDA's report, is the absence of a significant difference in the rate and extent that an active ingredient in pharmaceutical equivalents has contact with the site of the drug's action. The two drugs must also have the same dosing and similar conditions to be able to compare and approve the two for bioequivalence.

For a generic drug to be bioequivalent to a name-brand version, the drug manufacturer must get the U.S. Food and Drug Administration’s (FDA) stamp of approval. The drug company must prove the generic is pharmaceutically equal to the name-brand version. A drug maker must also get FDA approval before marketing or selling a different version of an approved drug. For example, it must prove a once-a-week tablet is bioequivalent to a daily tablet.

In addition, the FDA has different bioequivalence standards depending on whether the drug is taken as a pill, injection, patch, inhaler, or through another method. When a generic drug is not bioequivalent to the name-brand version, it might still be approved for another use, but not be approved as a substitute for the name-brand version.

The Path to Bioequivalence

Bioequivalence doesn't require the full clinical trial process that the name-brand version had to go through. Instead, generic drugs only have to be bioequivalent, which means the company applying for approval must perform the following steps:

• Test the generic drug against the brand-name drug on two small groups of test subjects.
• Draw timed blood samples from each patient.
• Demonstrate through statistical analysis that any difference in the drug’s bioavailability in participants taking the brand name version versus participants taking the generic version is not clinically significant.

It is easier to make a bioequivalent form of a traditional pill or injectable drug than to make a bioequivalent form of a biologic drug. As a result, the generic versions of biologic drugs, called “biosimilars,” may have to undergo clinical trials to gain approval.

Special Considerations

While bioequivalent drugs offer patients many benefits, some concerns still remain. Bioequivalence problems have been reported by physicians and patients that many approved generic drugs do not have the same desired impact as their branded counterparts. Certain classes are more prone to these discrepancies from specific chemical reactions.

Some of these include poorly absorbed drugs, chiral drugs, and other complex delivery mechanisms. Physicians are cautious in switching patients from branded to generic products, or between different generic manufacturers when prescribing ant-epileptic drugs and blood thinners.