FDA Grants AB Rating to 505b2 NDA Generic

AB Rating 505b2 NDA Generic

FDA recently granted a therapeutic equivalence (TE) rating of AB to a “generic” version of an innovator product approved via a 505b2 NDA.  In July 2014, FDA granted the AB rating to Perrigo’s 1% testosterone gel drug product (NDA 203098) approved in January 2013, and a BX rating to Teva’s (NDA 202763) approved in February 2012.  Each are versions of AbbVie’s Androgel® and employed 505(b)(2) submissions citing AndroGel® as their reference listed drugs (RLD).  Teva’s version was found to be bioinequivalent to AndroGel®, hence the BX rating.  Upsher-Smith Laboratories has also received approval for a version of Auxilium’s Testim® (Vogelxo™; NDA 204399) in June 2014 using the same pathway, however FDA has not yet assigned a therapeutic equivalence (TE) rating.

So why is this news?  In order to be AB rated a drug must me therapeutically equivalent to its RLD.  However “If the proposed product is a duplicate of an already approved product, it should not be submitted as a 505(b)(2) application”.  In this case, all three were submitted as 505b2 NDAs, not ANDAs.  Why?  Most basically (there’s more), FDA required clinical safety studies, in “practical effect” removing them from ANDA consideration.

Interchangeability ratings for 505b2 NDA Generic

There have previously been special circumstances in which FDA has afforded interchangeability ratings for generic formulations using 505(b) and 505(b)(2) submissions, but these are few and far between.  For example, prior to the passage of the 1984 Hatch-Waxman amendments, literature based NDAs for certain generic formulations were provided AB ratings to the relevant innovator products.  Additionally, in the early 2000s, FDA took steps to address unapproved levothyroxine.  FDA allowed currently marketed products to remain in commerce pending approval of NDAs.  Various levothyroxine products approved with 505b2 NDAs and ANDAs are currently listed as therapeutic equivalent formulations relative to designated RLDs.

In the case of Perrigo’s product, FDA issued no TE rating at all upon approval.  Consequently, Perrigo sued FDA, seeking a TE rating.  In the meantime, AbbVie and Auxilium filed Citizen Petitions requesting that FDA employ the rule-making process before making TE decisions on “generics” approved via the 505(b)(2) pathway.  On July 23, 2014 FDA responded to the Citizen Petitions, refusing to invoke the rulemaking process before making the decisions.  In their response FDA also granted the AB rating to Perrigo.  The rest is history…for now anyway.  PDG will continue to monitor and provide updates as events unfold.

Determining which pathway may be the best fit for your drug development program can be a complex decision. PDG will help you strategically navigate intellectual property concerns, the availability and quality of data from reference products, the scientific literature, FDA, other regulatory agencies and other sources to evaluate the various options for development and commercialization of your drug product. Contact us.