Adams Respiratory Therapeutics announced that it received an Approvable letter from FDA on 10/29/07 for its guaifenesin 600/1200 mg and codeine phosphate 30/60 mg extended-release bi-layer tablets. The release indicates that the FDA needed additional data to support the use of the product with food.
The proposed product is one of several currently on the market that the FDA considers to be unapproved. By Nov. 26, 2007, manufacturers of unapproved timed-release guaifenesin combination products must cease retail distribution of their product. This product has often been referred to as DESI, but the combination was never reviewed under this statute.
What Adams is doing is getting a 505(b)(2) approval and banking on FDA removing all of the competitors.
So what does Adams need to do to get its product approved? Per FDA guidance, all modified/extended release products must have their pharmacokinetic profiles assessed under both fasted and fed conditions. Maybe Adams didn’t do this or maybe the study design or results were deficient. Should be straightforward to remedy. Unlike an ANDA where fed studies comparing the test to reference product give sponsors fits due to the difficulty of passing the 80 -125% ratio limits, an NDA has no such limits. The purpose of a fed study, per 320.25(f) is to determine if the following conditions are met:
– The drug product meets the controlled-release claims made for it.
– The BA profile established for the drug product rules out the occurrence of any dose dumping.
– The drug product’s steady-state performance is equivalent to a currently marketed noncontrolled release or controlled-release drug product that contains the same active drug ingredient or therapeutic moiety and that is subject to an approved full NDA.
– The drug product’s formulation provides consistent pharmacokinetic performance between individual dosage units.
The data will be used to provide dosing recommendations on the label. Such studies under an NDA are usually done with 12 healthy people, comparing the pharmacokinetics under fed and fasted states.
Other useful references for extended/controlled/modified release oral drug products:
In Vitro/In Vivo Correlelations