Extended-release drug products studies

This guidance recommends that the following BA studies be conducted for an extended-release drug product submitted as an NDA ... 

BE studies are recommended when substantial changes in the components or composition and/or method of manufacture for an extended-release drug product occur between the to-be-marketed NDA dosage form and the clinical trial material. 

An NDA can be submitted for a previously unapproved new molecular entity, or for a new salt, new ester, prodrug, or other noncovalent derivative of a previously approved new molecular entity, formulated as a modihed-release drug product. The first modified-release drug product for a previously approved immediate-release drug product should be submitted as an NDA. Subsequent modified-release products that are pharmaceutically equivalent and bioequivalent to the listed drug product should be submitted as ANDAs. BA requirements for the NDA of an extended-release product are listed in 320.25(f). The purpose of an in vivo BA study for which a controlled-release claim is made is to determine if all of the following conditions are met. 

The study described here has a very complex design for its exploratory approach. It combines four different extended release formulations, each tested under fasting and non-fasting conditions, and compares the results to the immediate release drug product as the reference formulation. The bilayer tablets combines an immediate release component and an extended release component in one vehicle. In this project a close cooperation between the galenics department and the clinical pharmacokinetic function was mandatory. The in vitro/in vivo correlation was done by means of the deconvolution which is an appropriate surrogate to describe the in vivo dissolution. 

For an extended-release dosage form, at least three test time points are chosen to characterize the in vitro drug-release profile for the routine batch-to-batch quality control for approved products. Additional sampling times may be required for formulation development studies, biopharmaceutical evaluations, and drug approval purposes. An early time... 

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