Per- and polyfluorinated active pharmaceutical ingredients: an overview and alternatives

What is it about?

Per- and polyfluoroalkyl substances (PFAS) are molecules containing at least one -CF₃ or -CF₂ group (OECD definition, 2021). They are often referred to as ‘forever chemicals’ because they either do not degrade themselves or are transformed into persistent degradation products such as trifluoroacetic acid (TFA), which also cannot be broken down to any significant extent. Their persistence and the associated unknown but anticipated long-term effects of PFAS on human and environmental health are giving rise to growing concern.

In 2023, a proposal to restrict PFAS was submitted to the European Chemicals Agency (ECHA) – however, biocides, plant protection products and medicinal products for human and veterinary use were exempted from this restriction as they are considered ‘essential’.

The paper presented, „Per- and polyfluorinated active pharmaceutical ingredients: Overview and alternatives“ , examines one such exemption – namely active pharmaceutical ingredients (APIs), which the OECD classifies as PFAS – and identifies alternatives for the pharmaceutical industry.

Key messages

The study systematically searched various databases and publications to identify, from the active pharmaceutical ingredients (APIs) listed therein, those that qualify as PFAS according to the OECD’s definition. The authors arrived at the following conclusions:

A total of 111 APIs were identified as PFAS.
Over 80 per cent of these PFAS are potential precursors of trifluoroacetic acid (TFA).
Alternatives exist for all of these active pharmaceutical ingredients – or are already being developed.
In Germany, prescribing authority – and thus the decision on the use of alternatives – lies with doctors.

Nevertheless, it can be stated that the existence of PFAS-free alternatives is, for Prof. Müller, a clear indication “that per- or polyfluorination is not strictly necessary from a pharmacological point of view.” (press release)

^{Figure 1: A graphical summary of the publication illustrating the methodology of the study: first, PFAS were identified in accordance with the OECD definition, and then classified according to their ATC (Anatomical Therapeutic Chemical) code. This classification was then used to identify potential alternatives [1].}

Significance

As reported recently in a Tagesschau feature, TFA has been classified as toxic to reproduction by an ECHA assessment body – furthermore, according to the assessment report, the substance can affect the thyroid and liver. Of particular concern in this context, alongside its persistence, is its high water solubility, which means that TFA can end up in soil, drinking water and rivers, amongst other places – TFA has also already been detected in plants and food.

Although a proposal to restrict PFAS has already been submitted to the European Chemicals Agency (ECHA), this proposal currently excludes, amongst other things, medicinal products, as they are classified as essential. The publication presented here challenges this classification as ‘essential’: as a PFAS-free alternative exists for almost every PFAS-containing medicinal product, the restriction could certainly be extended to include medicinal products. Thus, phasing out PFAS in what appears to be an essential field could serve as a precursor to a definitive restriction in non-essential fields.

Such an approach, which restricts the use of PFAS in the pharmaceutical sector, would be entirely in line with the principles of Sustainable Pharmacy: to achieve this, it is essential that environmental risks are not only documented in the authorisation process, but also influence decision-making and are taken into account in the development of new medicines.

The publication in question calls for more sustainable strategies in pharmaceutical research and industry – and highlights a wide range of opportunities for innovative medicines.

Research group

Prof. Dr. Michael Müller’s research group is based in Pharmaceutical and Medicinal Chemistry and operates at the interface between fundamental scientific research and sustainable pharmacy. The group’s main areas of research are biocatalysis and biosynthesis, diversity-oriented chemoenzymatic synthesis, environmental analysis, and ethics and sustainability.

The research priorities of the research group are biocatalysis and biosynthesis, sustainable pharmacy, and ethics and sustainability.

Johanna Greinke is a PhD student in the Müller research group. She analyses trifluoroacetate (TFA) in environmental samples from around the world and is researching pharmaceuticals as precursors of TFA as part of her work in sustainable pharmacy.

Publication

[1] Johanna Greinke, Petra Mußler, Gerd Maack, Martin J. Hug, Michael Müller, Gunther Speichert, Per- and polyfluorinated active pharmaceutical ingredients: Overview and alternatives, Sustainable Chemistry and Pharmacy, Volume 52, 2026, 102416, ISSN 2352-5541, https://doi.org/10.1016/j.scp.2026.102416.