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Researchers Call to Modernize Bioequivalence Standards

Posted 14 December 2015 | By Michael Mezher 

Researchers Call to Modernize Bioequivalence Standards

A group of researchers are calling on the US Food and Drug Administration (FDA) to update generic drug regulations, warning that "outdated" bioequivalence standards threaten patient safety.

In a paper published in Trends in Pharmacological Sciences last week, the group said that in some cases, switching between branded drugs and their generic counterparts can cause significant issues.

This, the authors say, is because the determinations of bioequivalence can result in slight variations between an innovator and generic product, "which may result in two allegedly bioequivalent products not being interchangeable."

The authors also suggest that FDA should make bioequivalence data used to support generic approvals publicly available. They argue that more transparency would "offset some of the concerns and enable physicians and consumers to make better choices."


Since the passage of the Hatch-Waxman Act in 1984, companies have been able to register generic drugs in the US by demonstrating bioequivalence to the innovative product, without conducting clinical studies.

According to FDA, nearly 80% of all prescriptions filled in the US are for generic drugs, which the agency says cost 80-85% less than their branded counterparts.

Under current regulations, drugs are considered to be bioequivalent "if they are pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption do not show a significant difference when administered at the same molar dose."

Examples of Issues

According to the authors, FDA does not always consider certain factors when reviewing a generic for bioequivalence, such as the time it takes for a product to reach maximal concentration in the body.

In one case, numerous patients reported experiencing issues after switching between the 300mg extended release forms of the antidepressant Wellbutrin and its generic counterpart Budeprion. The two formulations were initially found to be bioequivalent, however, a subsequent study by FDA found the generic version failed to reach the same maximum concentration as the branded version. In that case, FDA determined that Budeprion XL 300 was not therapeutically equivalent to Wellbutrin LX 300 and the product was eventually taken off the market.

The authors also point to specific therapeutic areas, such as post-transplantation immunosuppression and epilepsy, where experts have observed issues when switching between brands of drugs.

Another issue, the authors point out, is that patients and their physicians are not always made aware when a pharmacist switches their prescription for a generic version.

Additionally, due to shortages and fluctuating prices, pharmacies often end up purchasing drugs made by different generic manufacturers, the risks of which have not been adequately studied, the authors write.


Trends in Pharmacological Sciences

Categories: Regulatory News

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