Glen Elliott, MD, PhD
Editor-in-chief, The Carlat Child Psychiatry Report
In November 2016, the FDA announced that it was requiring two companies to withdraw their generic versions of Concerta (OROS methylphenidate) because of efficacy concerns. Such actions are quite unusual, and when they occur, they tend to shake doctors’ confidence in the generic drug system—which branded drug companies are often eager to encourage. But the Concerta case is hardly an indictment of generic drugs, or even of generic stimulants. Let’s dig a little deeper for some insight into the generic drug process.
Concerta was originally developed and marketed by Janssen Pharmaceuticals (a division of Johnson and Johnson). In 2010, the company lost its marketing exclusivity after its patent expired, and subsequently other companies manufactured generic versions. In approving generic products, the FDA mostly evaluates data showing that the generic formulation is “bioequivalent” to the brand product. This means both that the molecules are identical, and that the rate and extent of drug absorption is not significantly different. The FDA uses the designation “AB” for generics that are bioequivalent to brand, and “BX” for generics that are not equivalent and therefore not substitutable at pharmacies. Sometimes equivalency problems are discovered after a generic drug has been approved (a recent example is bupropion SR).
By 2013, a total of three companies, Actavis, Mallinckrodt, and Kudco, had received FDA approval to sell generic versions of Concerta, with all three generics classified as AB. But in December 2013, the FDA announced that it had received reports of lack of therapeutic effects with generic Concerta pills made by Mallinckrodt and Kudco (not the Actavis version of Concerta, whose bioequivalence has never been questioned). The reports from patients and physicians were specifically about duration of action, with the Mallinckrodt and Kudco products lasting for shorter periods than brand-name Concerta. This should not have been a surprise, because the companies did not have access to the OROS technology that acts as an osmotic pump but rather relied on coated-bead and bilayer technology (the Actavis generic uses the osmotic delivery system).
At the time, the FDA did not take any regulatory action, but said it would monitor and evaluate the issue. However, as more reports validated these concerns, in 2014, the FDA reclassified the Mallinckrodt and Kudco generics to BX, ie, therapeutically nonequivalent. The FDA allowed continued sales of both products, but asked the manufacturers to consider either voluntarily withdrawing them from the market or submitting more bioequivalence data. Neither company complied with the FDA’s suggestions, though—in fact, Mallinckrodt instead opted to sue the FDA, a suit that was later dismissed by a Maryland federal judge.
In November 2016, presumably concluding that the companies were being intransigent, the FDA ordered that the two generic products be withdrawn. However, this process may take some time, and we recommend that you specify the manufacturer as Actavis on scripts when you prescribe generic Concerta.
The take-home lesson for the clinician: In the case of Concerta, not all generics are created equal. But we need to be clear that this was not a case of an adulterated or fake product. There were never any safety concerns, and Mallinckrodt and Kudco were selling genuine methylphenidate in a long-acting version—just not as long-acting as Concerta.