Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global Regulatory Expectations?

Abstract

Abstract. The objective of this article is to compare and contrast the international expectations associated with the model-independent similarity factor approach to comparing dissolution profiles. This comparison highlights globally divergent regulatory requirements to meet local dissolution similarity requirements. In effect, experiments customized to meet the current international regulatory expectations for dissolution and drug release unnecessarily increase manufacturing costs, hinder science and risk-based approaches, increase collective regulatory burden, reduce continuous improvement and innovation, and potentially delay patient access to urgently needed medication. Comparative assessment of regulatory differences in applying dissolution to demonstrate product similarity is crucial to reduce non-scientifically justified experiments and foster collaborative harmonization among global regulatory health authorities and the pharmaceutical industry.

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“…A similarity factor f 2 test was used to determine differences between the in vitro dissolution profiles for the LCIG‐HV and LCIG‐LV commercial formulation. The methodology for the f 2 test has been previously described …”

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“…that focused on the necessity to harmonize dissolution guidances to enable timely access to medicines. She discussed the globally divergent regulatory requirements for bioequivalence, multipurpose dissolution guidances, and the complexity of global dissolution filing strategies, along with the impact on research, innovation, and access to medicines (2). She provided business case examples along with a powerful analysis of the multipurpose applicability of dissolution guidance explaining how complexity increases when referral to various guidance documents (e.g., method development, post-approval changes, biowaiver for additional strengths) is needed.…”