Per- and polyfluorinated active pharmaceutical ingredients: Overview and alternatives

Abstract

Per- and polyfluoroalkyl substances (PFAS) are raising concern due to their inherent persistence and mostly unknown long-term consequences for human and environmental health. Through providing convenient properties, polyfluorination is used in a variety of areas. The restriction on PFAS proposed to ECHA in 2023 would affect molecules with either a –CF3 or a –CF2– group, following the definition of PFAS by the OECD in 2021. Polyfluorinated pharmaceuticals were excluded a priori even though polyfluorination can lead to persistence and active agents are prone to cause adverse effects in the environment. There has been no research on polyfluorinated pharmaceuticals and their alternatives focusing on prevention or reduction of their use so far. We identified 111 active pharmaceutical ingredients (APIs) for human use which are PFAS according to the current OECD definition. They are distributed across almost all indications, 84% of them being potential precursors of trifluoroacetic acid/trifluoroacetate (TFA). Additionally, we identified 28 PFAS-APIs which are used as veterinary pharmaceuticals, 82% of which could eventually release TFA. The majority of PFAS-APIs has readily available non-PFAS alternatives. For the nine APIs in human medicine that don't, there are new drugs without polyfluorination being developed. Contrary to common belief of polyfluorinated APIs being essential we show that none of the 111 PFAS-APIs is without nonfluorinated alternatives. Therefore, APIs need to be reassessed for their persistence and environmental hazards just like any other chemicals. In order to achieve Sustainable Pharmacy, it is essential that environmental risks are not only documented in the authorisation process, but also have an influence on decision making and are considered in the development of new drugs.