In certain circumstances (see also section 13), equivalence may be assessed by the use of in vitro dissolution testing. Examples where dissolution testing may be considered acceptable include:
(a) Drugs for which in vivo studies (see above) are not required;
(b) Different strengths of a multisource formulation, when the pharmaceutical products are manufactured by the same manufacturer at the same manufacturing site, where:
! the qualitative composition between the strengths is essentially the same;
! the ratio of active ingredients and excipients between the strengths is essentially the same, or, in the case of small strengths, the ratio between the excipients is the same;
! an appropriate equivalence study has been performed on at least one of the strengths of the formulation (usually the highest strength unless a lower strength is chosen for reasons of safety); and
! in case of systemic availability pharmacokinetics have been shown to be linear over the therapeutic dose range.
Although this guideline comments primarily on registration requirements for multisource pharmaceutical products, it is to be noted that in vitro dissolution testing may also be suitable to confirm unchanged product quality and performance characteristics with minor formulation or manufacturing changes after approval (see Part Six).