Clearance and retention of leachables in ultrafiltration and diafiltration applications.

Ultrafiltration/diafiltration (UF/DF) operations are used to clear a broad range of process equipment-related leachables (PERLs) from process streams. While previous UF/DF studies have demonstrated efficient clearance by dilution and permeate removal, the contribution of adsorption to and retention within process-contact materials has remained largely unexplored. This study comprehensively investigated the clearance and retention of representative PERLs during UF/DF, referred to here as the "fate of leachables" concept. Controlled spiking experiments and adsorption studies were combined with extraction-based mass balances and kinetic modelling. Hydrophilic compounds behaved close to theoretical expectations and were efficiently removed via the permeate stream. In contrast, hydrophobic PERLs showed non-ideal clearance behaviour due to adsorption to contact materials, such as silicone tubing and polyethersulfone membranes, migration into polymer phases, and protein association. Most compounds were recovered by organic extraction, suggesting predominantly reversible surface adsorption, whereas DtBP showed incomplete recovery, indicating stronger system retention and/or migration into polymer phases. A source-sink model adapted from the Bateman equation successfully described the observed concentration profiles. These findings extend existing UF/DF clearance concepts by identifying process-contact materials as active sinks for PERLs and provide a mechanistic framework for more realistic prediction of PERL fate and interpretation of extractables and leachables data under manufacturing-relevant conditions.