21st Century Bioequivalence: How do you spell "Integrity?"

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  • 05/18/2015

Much discussion about pharmaceutical quality at the FDA of late (Drug Quality: If you can’t measure it, it doesn’t count, The silent “n” of PDUFA) – and specifically about a more 21st century view of bioequivalence.

And appropriately so. But is the agency doing the right thing the right way? Consider Concerta. Will the courts follow the chevron deference route or tell the FDA to put it on paper?

Here’s the skinny from the Wall Street Journal:

FDA and Mallinckrodt Lock Horns Over the Right to Sell Generic Concerta

By Ed Silverman

To what extent should the FDA be allowed to reclassify a generic drug when the agency believes it is no longer equivalent to the brand-name version?

The issue is being raised in an unusual lawsuit claiming the agency overstepped its bounds by deciding two generic drugs used to treat ADHD should no longer be substituted for the widely used Concerta treatment.

And the outcome of the case may have implications for generic drug makers and the FDA.

Here’s what happened: After reviewing side effect reports indicating some patients were not getting the expected benefit, the FDA analyzed the generics, which are made by Mallinckrodt and UCB, and found the drugs were not bioequivalent. This meant the drugs were not absorbed in the body in the same way as Johnson & Johnson’s Concerta or an authorized version also made by J&J, but sold by Actavis.

So last November, the FDA changed the ratings for the two generic versions, which contain the same active ingredient as Concerta. As a result, the two generics could no longer be automatically substituted for Concerta at pharmacy counters. The agency also gave the drug makers six months to provide data showing bioequivalency to Concerta or their drugs should be withdrawn from the market.

The deadline passed this week, but the generics remain available and it is unclear how the FDA will proceed. An agency spokeswoman would not comment. A spokeswoman for UCB says its Kudco unit, which sells generic Concerta, is working with the FDA to meet its requirement. Mallinckrodt, however, is a different story. The drug maker is not showing any signs of complying with the agency mandate.

Why? In its lawsuit, which was filed last November, Mallinckrodt challenged the authority of the agency to reclassify its generic by arguing the FDA failed to provide sufficient notice of its decision and violated its Constitutional rights. Moreover, Mallinckrodt notes the FDA acknowledged there are no safety issues and patients should continue taking the generics if they are not experiencing problems.

As a result, Mallinckrodt chief executive Mark Trudeau told Wall Street analysts last week that, while his company is talking to the FDA, the drug maker plans to sell its generic for the “foreseeable future.” A Mallinckrodt spokeswoman reiterated his remarks in response to questions, and an FDA spokeswoman would not comment, citing litigation.

Meanwhile, the generics can still be found in plenty of pharmacies. CVS and Rite Aid, for instance, stock the drugs, say spokespeople for the retailers. As Trudeau noted, the Mallinckrodt generic can be prescribed in “virtually every state in the nation,” depending upon state regulations.

As a result, new ADHD patients may also be prescribed a drug that is not therapeutically equivalent to brand-name Concerta. This is especially likely at a time when generics are valued as lower-priced alternatives.

This is not the first time the FDA has reclassified generic drugs over equivalency. In 2012, the agency changed ratings for some generic antidepressants. But the Mallinckrodt challenge is a first. Whether the drug maker succeeds is unclear.

But for now, the episode poses a dilemma, because the showdown has inadvertently produced another category of generic Concerta. A key issue is the extent to which the FDA can serve the public interest and retain the confidence of the American public.

“In a broad sense,” says Kurt Karst, an attorney who specializes in FDA regulatory matters, “this raises questions about the integrity of the generic drug system in the U.S.”


Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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