Guidance on Waiver of In vivo Bioequivalence Requirements

According to the BCS, a product is classified as Class I if it is both highly soluble and highly permeable, Class II if it is highly soluble but poorly permeable, Class III if it is poorly soluble but highly permeable, and Class IV if it is both poorly soluble and poorly permeable. The Ethiopian Food, Medicine and Healthcare Administration and Control Authority (EFMHACA) has established guidelines for the waiver of in vivo bioequivalence requirements for pharmaceutical products. The guidelines state that a biowaiver can be applied for pharmaceutical products that meet the requirements for pharmaceutical equivalence and similarity in comparative dissolution tests. The BCS-based biowaiver is applicable for immediate release solid oral dosage forms, dose-proportionality formulations, and significant post-approval changes. The list of APIs eligible and not eligible for a BCS-based biowaiver is outlined in Annex III of the WHO TRS 937. The guidelines also specify that data supporting the API solubility or permeability class is not necessary to provide in the application. Biowaivers can be applied in various areas, including formulation development for new finished pharmaceutical products, line extensions, formulation development of generic finished pharmaceutical products, and post-approval changes. The guidelines also define key terms such as biowaiver, comparator product, fixed-dose combination, and narrow therapeutic index drug products. Pharmaceutical equivalence is a critical requirement for biowaivers, and finished pharmaceutical products are considered pharmaceutical equivalents if they contain the same molar amount of the active pharmaceutical ingredient (API) and have the same strength, dosage form, and route of administration. The guidelines also specify that the comparator product should be the innovator product for which efficacy, safety, and quality have been established. The EFMHACA guidelines for biowaivers are based on the WHO guidelines on bioavailability and bioequivalence, including the WHO TRS 992 and WHO TRS 937 annex 7 & 8. The guidelines are intended to simplify the pharmaceutical product approval process and reduce the time required to bring new pharmaceutical products to market. In terms of implementation, the guidelines specify that the application for a biowaiver should include data on comparative dissolution between the different strengths of the test product and against the respective strengths of the comparator product. The guidelines also specify that the biowaiver application form should be completed in accordance with Annex I and Annex II of the guidelines. Overall, the EFMHACA guidelines for biowaivers provide a framework for the waiver of in vivo bioequivalence requirements for pharmaceutical products, with the goal of simplifying the pharmaceutical product approval process and reducing the time required to bring new pharmaceutical products to market.