The need for additional metrics to assess therapeutic equivalence of some multiphasic modified-release products.

BACKGROUND

Advisory committees for the regulatory agencies of the United States (US Food and Drug Administration [FDA]) and Canada (Health Canada) recently considered issues associated with the determination of bioequivalence for some multiphasic modified-release (MR) drug products. The FDA has concluded that because of the complicated properties of some multiphasic MR products, additional metrics such as partial AUC are required for their assessment, whereas an advisory panel of Health Canada has decided that the current metrics are adequate and sufficient.

POSITION STATEMENT

The authors agree with the conclusion of the FDA that additional metrics are required.

DISCUSSION

The rationales considered by the advisory committees are discussed and commented upon. It is suggested that without applying an additional metric such as partial AUC, some multiphasic MR drug products might falsely be assumed to be therapeutically equivalent and unexpected clinical effects may occur.