The Synthetic Role of PFAS in Drug Substance Manufacturing: An IQ Consortium Working Group Review on the Potential Impact of PFAS Restrictions on Patient Access to Medicines

Per- and polyfluoroalkyl substances (PFAS) have been widely used in consumer and industrial applications including the pharmaceutical industry. This widespread adoption throughout society has recently come under scrutiny due to human health and environmental concerns associated with the toxicity and environmental persistence of certain PFAS. Within the IQ Consortium, a Working Group (WG) focusing on drug substance manufacturing has been established to assess the prevalence of PFAS in commercial drug substance manufacturing and the potential impact of PFAS regulations on patient access to medicines. To address gaps in current definitions, we introduce a functional classification—visible, contributing, and invisible PFAS—to distinguish PFAS present in marketed active pharmaceutical ingredients (APIs), those essential for installing PFAS moieties into APIs, and reagents or solvents enabling synthesis without remaining in the final product. Survey data from IQ Consortium member companies and literature analysis confirm extensive PFAS use and presence across the drug substance supply chain. These findings highlight that broad PFAS restrictions could disrupt manufacturing, necessitate significant process redevelopment and regulatory revalidation, and jeopardize continuity of supply. Proactive engagement and risk mitigation strategies are critical to balance environmental objectives with uninterrupted patient access to essential medicines.