Mallinckrodt Sues FDA After Agency Downgrades Therapeutic Equivalence Rating for Generic CONCERTA

November 19, 2014

By Kurt R. Karst –       

Earlier this week, Mallinckrodt Inc. (“Mallinckrodt”) filed a Complaint and Motion for Temporary Restraining Order (later supplemented) in the U.S. District Court for the District of Maryland challenging FDA’s November 12, 2014 decision to downgrade from “AB” to “BX” the Therapeutic Equivalence (“TE”) rating for the company’s generic version of CONCERTA (methylphenidate HCl) Extended-Release Tablets, 27 mg, 36 mg, and 54 mg, which the Agency approved on December 28, 2012 under ANDA 202608.  FDA also downgraded the TE rating for another generic version of CONCERTA approved on July 9, 2013 under ANDA 091695 and marketed by Kudco Ireland Ltd.  Both drugs were downgraded after FDA issued a revised ANDA bioequivalence guidance earlier this month, and after FDA stated, based on “[a]n analysis of adverse event reports, an internal FDA re-examination of previously submitted data, and FDA laboratory tests,” that the generic versions of CONCERTA “have raised concerns that the products may not produce the same therapeutic benefits for some patients as [CONCERTA].”  FDA has asked both ANDA sponsors to either confirm, within 6 months, the bioequivalence of their products using the Agency’s revised bioequivalence standards, or voluntarily withdraw their products from the market.

By way of background, TE ratings are used to determine the substitutability of two drug products.  Pharmaceutically equivalent prescription drug products (i.e., generally drug products in the same strength, route of administration, dosage form, and containing the same active ingredient) are identified in the Orange Book with either an “A” or “B” therapeutic equivalence code designation.  “A-rated” drug products are considered to be to therapeutically equivalent to other pharmaceutically equivalent products, because there are no known or suspected bioequivalence problems, or such problems have been resolved with adequate evidence supporting bioequivalence.  “B-rated” drug products are not considered to be therapeutically equivalent to other pharmaceutically equivalent drug products, because actual or potential bioequivalence problems identified by FDA have not been resolved by adequate bioequivalence evidence. 

Drug products assigned an “A” rating fall under one of two categories: (1) those active ingredients or dosage forms for which no in vivo bioequivalence issue is known or suspected, and for which bioequivalence to the Reference Listed Drug (“RLD”) is presumed and considered self-evident based on other data in an application or by a showing that an acceptable in vitro dissolution standard is met; or (2) those active ingredients or dosage forms presenting a potential bioequivalence problem, but the applicant’s approved application contains adequate scientific evidence establishing (through in vivo and/or in vitro studies) the bioequivalence of the product to a selected RLD.  Drug products that fall under the first category are assigned a therapeutic equivalence code depending on the dosage form.  These codes include “AA,” “AN,” “AO,” “AP,” or “AT.”  Drug products that fall under the second category are coded “AB” (the most common code assignment).

Drug products assigned a “B” rating are designated “BC,” “BD,” “BE,” “BN,” “BP,” “BR,” “BS,” “BT,” “BX,” or “B*,” generally according to dosage form.  According to the Orange Book Preface, a “BX” code is “assigned to specific drug products for which the data that have been reviewed by the Agency are insufficient to determine therapeutic equivalence under the policies stated in this document.  In these situations, the drug products are presumed to be therapeutically inequivalent until the Agency has determined that there is adequate information to make a full evaluation of therapeutic equivalence.”

In recent year, FDA actions concerning TE ratings have been the focus of some controversy – generally in the context of 505(b)(2) applications – with a couple of Citizen Petitions and a lawsuit against FDA (see our previous posts here and here).  FDA also downgraded the TE ratings, and then withdrew the approvals, of two ANDAs for Bupropion Hydrochloride Extended-Release Tablets, 300 mg, after concerns about therapeutic equivalence were raised (see here and here).

According to Mallinckrodt, FDA’s TE rating downgrade for generic CONCERTA effectively takes the drug off the market because TE ratings are used in many states (see here) for purposes of substitution.  “That determination by FDA means that (depending on the jurisdiction) it is either unlawful or unacceptably risky for pharmacists to fill a prescription by substituting Mallinckrodt’s generic for the brand-name drug Concerta®,” says Mallinckrodt. 

Mallinckrodt also alleges that FDA exceeded its statutory authority by effectively taking the company’s drug off the market without providing Mallinckrodt with a hearing. “The FFDCA provides only one mechanism for taking a generic drug off the market: withdrawing (or suspending) ANDA approval under 21 U.S.C. § 355(e). . . . FDA has no statutory authority to take a drug off the market through other actions not specified in section 355(e).”  Citing the DC Circuit Court’s recent decision in Ivy Sports Medicine, LLC v. Burwell, 767 F.3d 81 (D.C. Cir 2014), pet. for reh’g en banc filed Nov. 11, 2014 (see our previous post here), Mallinckrodt says that that conclusion “flows directly from a recent D.C. Circuit decision construing the parallel statutory requirements governing FDA’s authority to remove a medical device from the market (following an earlier FDA decision that authorized marketing the device).”

Mallinckrodt asserts that FDA’s action has violated the company’s rights under the Fifth Amendment to the U.S. Constitution.  “The statutory hearing rights . . . derive from an underlying constitutional right to notice and a hearing guaranteed by the Fifth Amendment’s Due Process Clause. . . .  When it reclassified Mallinckrodt’s methylphenidate ER, FDA eviscerated the company’s property right in its ANDA by effectively taking the drug of the market.  FDA had no constitutional authority to impair Mallinckrodt’s property right without giving Mallinckrodt notice and an opportunity to be heard.”

Mallinckrodt’s five-count Complaint seeks both injunctive and declaratory relief from the court, including an injunction setting aside FDA’s actions, and prohibiting its future actions, and a declaratory judgment declaring that FDA has acted unlawfully. 


  • On November 19th, the court issued a notice confirming that a hearing on Mallinckrodt's Motion for Temporary Restraining Order is scheduled for Tuesday, November 25, 2014, at 9:00 AM before Judge Deborah K. Chasanow.  FDA's Opposition is due by 4 p.m. on November 20th.