The FDA has ordered a hearing on whether a generic Concerta lasts as long as its label claims, nearly ten years after it proposed to pull the approval

Read the docket number. It opens with 2016.

The Food and Drug Administration filed a notice for public inspection on Wednesday ordering a formal evidentiary public hearing on whether to withdraw approval of ANDA 091695, the abbreviated new drug application held by Kremers Urban Pharmaceuticals for methylphenidate hydrochloride extended-release tablets, a generic of Concerta. The Center for Drug Evaluation and Research proposed that withdrawal on 18 October 2016. Kremers asked for a hearing on 10 November 2016. The notice granting one is dated this week.

Concerta itself is NDA 021121, held by Janssen and approved on 1 August 2000, and its labelling claims a 12-hour duration of effectiveness. That number is the whole dispute.

What went wrong with the data

FDA approved the Kremers application on 9 July 2013 for the 18 mg and 27 mg strengths and on 23 September 2013 for the 36 mg and 54 mg strengths, on a finding of bioequivalence rather than on clinical studies of its own. The testing followed a draft guidance issued in September 2012.

Then the agency received adverse event reports describing what the notice calls an insufficient therapeutic effect, "particularly during the latter part of the 12-hour period after dosing." CDER opened a tracked safety issue, reconsidered what bioequivalence to a 12-hour product requires, and issued a revised draft guidance on 6 November 2014 saying that exposure had to match across the entire therapeutic time course.

Reanalysed against that standard, the original data on the 54 mg strength failed at 7 to 12 hours under fasting conditions and at 8 to 12 hours under fed conditions. New data Kremers submitted in June 2015 failed at 8 to 12 hours fed.

The hearing, and its limits

Administrative Law Judge Kourtney LeBlanc of the Department of Health and Human Services Departmental Appeals Board will preside. The parties are CDER and Kremers, and under 21 CFR 12.87(d) the burden of proof rests on Kremers, the party contesting withdrawal. The statutory ground is section 505(e)(3) of the Federal Food, Drug, and Cosmetic Act, which requires FDA to withdraw an approval where new information leaves a lack of substantial evidence that a drug does what its labelling says.

CDER identified two sub-issues. Whether matching exposure across the whole 12 hours is necessary, and whether the Kremers product achieves it. The Office of the Commissioner granted a hearing outright on the second. On the first it granted one only so far as it raises a factual or scientific question, because that sub-issue reads as a question of law about the meaning of bioequivalence in section 505(j)(2)(A)(iv), and 21 CFR 12.24(b)(1) says a hearing will not be granted on issues of policy or law.

A prehearing conference is set for 45 days after publication, by videoconference, at 10 a.m. Eastern. The hearing date will be set there. Notices of participation are due 30 days after publication and disclosures 60 days. The hearing will be streamed on the department's public live page.

The document gives no calendar dates for any of it, only the intervals, because publication is scheduled for Thursday.