FDA issues guidance on bioequivalence studies with pharmacokinetic endpoints

The FDA has published draft guidance on bioequivalence (BE) studies involving pharmacokinetic endpoints involving drugs under an abbreviated new drug application (ANDA), revising and replacing two previous guidance documents.

The guidance highlights 12 areas for consideration when using pharmacokinetic studies to establish bioequivalence, plus general considerations relating to in vitro, pharmacodynamic and comparative clinical studies.

FDA recommends use of a two-period, two-sequence, two-treatment, single-dose, crossover study design, a single-dose parallel study design, or a replicate study design for BE studies. For most dosage forms that release drug intended to be systemically available, the guidance recommends a two-period, two-sequence, two-treatment, single-dose, crossover study using healthy subjects. A replicate crossover study may be an appropriate alternative to the parallel or non-replicate crossover study described above, and can be conducted as either a partial (three-way) or full (four-way) replication of treatment.

Separate guidance will soon be available that will address BA and BE studies for INDs, NDAs, and NDA supplements.