Comparative in vitro dissolution studies may be useful in the documentation of equivalence between two multisource pharmaceutical products. However, because of the many limitations associated with the use of in vitro dissolution in the documentation of equivalence it is recommended in these guidelines that its application for this purpose should be kept to a minimum. In vitro dissolution testing as the sole documentation of equivalence is therefore not applicable to the drugs and dosage forms listed as examples (a) - (e) on In vivo studies (9), but should be reserved for rapidly dissolving drug products.1 When the multisource test and reference products both dissolve with sufficient rapidity (e.g. >80% in 15 minutes), their in vivo equivalence may be presumed. Approval of multisource formulations by the use of comparative in vitro dissolution studies should be based on the generation of comparative dissolution profiles rather than single-point dissolution tests, as described in various pharmacopoeial compendia and other publications. Multiple dissolution test conditions and physiologically relevant media are recommended.
1 Where a drug substance and drug product do not dissolve with sufficient rapidity, as noted above, in vitro dissolution methods may still be used to document equivalence using appropriately validated dissolution methodology including an in vitro/in vivo correlation. Such methodology should be derived from the development and application of specifications and statistical methods to define non-equivalence. This may require formulations with different in vivo performance characteristics. With such formulations, discriminatory in vitro dissolution tests for use in equivalence studies may be developed. With these additional requirements, however, a standard in vivo bioequivalence study as described in section 7 may be preferable.