Bioequivalence and Bioavailability Forum

Hi Peter,

❝ The EU legal framework seems pretty clear, in that you can only use an RMP, for the BioEq study, approved/marketed in Europe.

You are right that only an originator’s product which was approved based on a full dossier in any member state of the European Economic Area (EEA = EU, Liechtenstein, Iceland, Norway) can be used as a reference in a generic application.¹

❝ Any thoughts on providing enough manufacturing evidence to claim EU and US RMPs are equivalent? or is this an absolute given the RMP must be manufactured and marketed in EU?

Some tried, all failed – even in cases where there is only one production site of the originator worldwide…
Currently impossible because it would require a change in the European legislation.² Of course, a ‘Global Comparator’ would be desirable in order reduce the number of human studies.^3–7 See also the references about ‘Adjusted Indirect Comparisons’.

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1. European Medicines Agency, Committee for Medicinal Products for Human Use. Guideline on the Investigation of Bioequivalence. London. 20 January 2010. Online.
   
2. European Parliament and Council. Directive 2001/83/EC on the Community code relating to medicinal products for human use. Article 10 2.(b) 6 November 2001, last amended 12 April 2022. Online.
   
3. Wang YL, Hsu LF. Evaluating the Feasibility of Use of a Foreign Reference Product for Generic Drug Applications: A Retrospective Pilot Study. Eur J Drug Metab Pharmacokinet. 2017; 42(6): 935–42. doi:10.1007/s13318-017-0409-y.
   
4. Gwaza L, Gordon J, Leufkens H, Stahl M, García-Arieta A. Global Harmonization of Comparator Products for Bio­equi­va­lence Studies. AAPS J. 2017; 19(3): 603–6. doi:10.1208/s12248-017-0068-6.
   
5. Almeida S. An opportunity or a mirage: Single global development for generic products. Presentation at: Bio­Bridges; Prague. 27 September 2019. Online.
   
6. Almeida S. Road Map to an International BE Reference Product? Pre­sen­ta­tion at: 4^th International GBHI Workshop; Bethesda, MD. 13 December 2019.
   
7. Almeida S. Single global development of generic medicines. Pre­sen­ta­tion at: me­di­ci­nes for europe, 2^nd BE Work­shop; Brussels. 26 April 2023.