Bioequivalence studies immediate-release drug product

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. 

Amidon, G.L. Lennernas, H. Shah, V.P. Crison, J.R. A theocratical basis for the biopharmaceutic drug classification the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 1995,12, 413-420. FDA Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, August 2000. 

The BCS was initially developed to provide a scientific approach for the granting of biowaivers that is, for allowing drug developers to replace certain bioequivalence clinical studies by accurate in vitro dissolution data (Yu et ak, 2002 Kalantzi et ak, 2005). The BCS was initially designed for immediate release products that are absorbed throughout the gastrointestinal tract. In addition to... 

Class 1 drugs must have wide therapeutic index, and their dissolution must be rapid for an in vivo bioequivalence study to be waived. An immediate release product is considered rapidly dissolving when not less than 85% of the labeled amount of the drug substance is dissolved within 30 minutes of using USP Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in a volume of 900 mL or less in each of the following media 0. IN HCl or simulated gastric fluid USP without enzymes, in a pH 4.5 buffer, and in a pH 6.8 buffer or simulated intestinal fluid USP without enzymes (29). 

Recently the FDA has proposed the waiver of bioequivalence studies for immediate-release solid oral dosage forms for a Class 1 drug substance based on the Biopharmaceutics Classification System (highly soluble and highly permeable) and for a rapidly dissolving product. ... 

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