A Survey of the Regulatory Requirements for the Acceptance of Foreign Comparator Products by Participating Regulators and Organizations of the International Generic Drug Regulators Programme

Abstract

The acceptance of foreign comparator products is the most limiting factor for the development and regulatory assessment of generic medicines marketed globally. Bioequivalence studies have to be repeated with the local comparator products of each jurisdiction because it is unknown if the comparators of the different countries are the same product, with the consequent duplication of efforts by regulators and industry alike. The regulatory requirements on the acceptability of foreign comparator products of oral dosage forms differ between countries participating in the Bioequivalence Working Group for Generics of the International Pharmaceutical Regulators Programme. Brazil, Colombia, the European Union member States, Japan, Mexico, South Korea and the United States only accept bioequivalence studies with their local comparator. In contrast, Australia, Canada, New Zealand, Singapore, South Africa, Switzerland and Taiwan accept studies with foreign comparators under certain conditions. Canada limits its use to highly soluble drugs with a wide therapeutic range in immediate release products. Australia requires a comparison of the quantitative composition. In contrast, there are fewer restrictions on the acceptance of foreign comparators in New Zealand, Singapore, South Africa, Switzerland and Taiwan. For the WHO Prequalification of Medicines and for developing generics of the essential medicines the WHO lists comparators from different countries. In conclusion, there is currently no consensus amongst regulators on the acceptability of foreign comparator products.

Barriers to generic antiseizure medication use: Results of a global survey by the International League Against Epilepsy Generic Substitution Task Force

“…This is complicated by the fact that there is no single international standard for the determination of bioequivalence, and approval of generic products and standards vary widely between countries. 23,24 Some professional pharmaceutical science organizations and the WHO have noted this to be a problem and have recommended international harmonization of definitions and standards for bioequivalence and generic product approval. [25][26][27][28] Many high-income countries, like the United States and several European countries, have strong regulatory controls, policies, and monitoring, which prevent poor quality or unproven generic products from being marketed.…”

“…As noted in the survey results, respondents from low‐income countries noted fewer regulatory controls. This is complicated by the fact that there is no single international standard for the determination of bioequivalence, and approval of generic products and standards vary widely between countries 23,24 . Some professional pharmaceutical science organizations and the WHO have noted this to be a problem and have recommended international harmonization of definitions and standards for bioequivalence and generic product approval 25–28 .…”

Impact of the European Union on access to medicines in low- and middle-income countries: A scoping review

“…One trend suggests that in order to assess the bioequivalence of local generics regulators, small and some mid-sized markets (e.g., South Africa) accept studies with foreign comparators that have been approved in founding members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (e.g., EU), whereas large-market regulators (e.g. Brazil, Mexico) do not [55] .…”

“…This review also demonstrates the key role of EMA in influencing LMIC pharmaceutical policy, both intentionally through the EUMeds4All/Article 58 procedure, and unintentionally when LMICs rely on EMA's regulatory actions. LMICs appear to rely on the EU's regulatory decisions (instead of WHO recommendations, for example) because companies marketing a new medicine may first seek the approval of a ‘stringent regulatory authority’ such as the EU, which serves as a basis for WHO pre-qualification (PQP) [17] , and because some LMIC regulators and WHO PQP require a foreign comparator for generic and/or biosimilar products [55] .…”