Generic Drugs Making Waves


Applied Clinical Trials

Applied Clinical TrialsApplied Clinical Trials-11-01-2012
Volume 21
Issue 11

In late August, the FDA elevated the Office of Generic Drugs to report directly to Janet Woodcock, the director of CDER.

In late August, the FDA elevated the Office of Generic Drugs to report directly to Janet Woodcock, the director of CDER. The move reflects that segment of the industry's importance in CDER. Specifically, that almost 80 percent of all prescriptions in the United States are now for generics.

On the heels of that announcement, FDA announced in early October that it had discovered budeprion XL 300 mg, manufactured by Impax (marketed by Teva) was not therapeutically equivalent to the reference drug That drug is Wellbutrin 300 mg, which is prescribed for major depressive disorder and for the prevention of seasonal affective disorder. Impax chose to withdraw the drug from the market. No other Wellbutrin XL 300-mg generics were involved.

Figure 1

The determination of bioequivalence for the 300-mg dose was actually never studied by Impax, and waived by FDA based on safety reasons when the generic was approved in December 2006. Rather, the data from the 150-mg dose was extrapolated and used for its approval for bioequivalency because it was determined testing the higher dose could cause seizures in healthy volunteers.

Figure 2

The FDA notes in its announcement that it received 85 postmarketing reports of adverse events or lack of an effect after patients switched from Wellbutrin to the budepiron between January and June 2007. However, the FDA said, "Reports of lack of effect were difficult to interpret given the natural course of depression in the treated population." In November 2007, the FDA asked Impax/Teva to conduct a bioequivalence study to compare the two drugs and doses, however, it was terminated in late 2011 by Impax/Teva because it could not meet the recruitment numbers.

In 2010, FDA decided to conduct its own direct bioequivalent study, with results available in August 2012. In the report, it asks "Why did it take FDA two years to complete the bioequivalence study?" The answer? One that should be familiar to most clinical trials professionals: "FDA worked to get funding for the study, designed the study, obtained approval from the Institutional Review Board for Protection of Human Subjects, recruited and enrolled healthy volunteers, conducted the study, developed an analytical method of analyzing the data, and completed its analysis of the study data."

So while the office is elevated, and under Generic Drug User Fee Amendments of 2012, FDA will receive $1.58 billion from generic drugmakers that were previously exempt, this is the first sticky situation involving a generic drug since the move. Prior to that the Associated Press reported that the FDA has only reversed approval on the equivalence of three drugs in the last five years.

And while this Wellbutrin issue came out during the same time as the meningitis outbreak and compounding issue, which had significant mainstream media coverage, this generic issue could have downstream effects with consumers. Specifically, FDA's consumer information about generics on its website—Figure 1 clearly states that the generic has the same quality and performance as the brand. And that they must be equivalent to the brand. On average the generic version costs 80 percent to 85 percent less than the branded version (Figure 2).

Biosimilars are not generics

According to the FDA's information for consumers on biosimilars, they are not generic versions of biological products. "The word 'generic' applies only to small-molecule drugs that are the same as, and bioequivalent to, an already-approved small-molecule drug regulated under the FD&C Act." Biosimilars rather are 'highly similar' to the reference biological product."

Apparently, FDA or CDER needs to spread the word on biosimilars. According to a recent report from Industry Standard Research, titled "Improving Patient Recruitment in Biosimilar Trials," ( respondents from investigative sites, roughly half are not familiar with biosimilars. However, they would be excited if a biosimilar protocol came across their desk. In addition, the ISR Report noted that the surveyed sites have conducted 19 studies in the past 24 months, and of those studies, five or six has been for a generic product, and one for a biosimilar.

—Lisa Henderson

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