A Practical Method for Inline-To-Offline Conversion in Extracorporeal Photopheresis

Extracorporeal photopheresis (ECP) is an established immunomodulatory therapy that is traditionally delivered using either "inline" systems, which integrate mononuclear cell (MNC) collection, photoactivation, and reinfusion, or "offline" platforms that allow greater processing flexibility but require dedicated irradiation equipment. Access to standalone UVA irradiators may be limited in clinical and research settings where cryopreservation of ECP-treated cells is required. In this study, we describe a practical hybrid approach that adapts the inline Amicus Blue Photopheresis System into an inline-to-offline workflow, enabling larger total blood volume processing, partial reinfusion, and cryopreservation of photoactivated MNCs. Using a fixed 200-mL MNC collection, followed by standard 8-methoxypsoralen administration and UVA irradiation, 50 mL was reinfused inline, while the remaining product was aliquoted for offline cryopreservation. This method has been implemented in the OPERA clinical trial (NCT05413005) and preserves procedural safety, product integrity, and operational simplicity. In summary, this approach enables offline capabilities within an inline ECP framework without requiring an independent UVA irradiator and expands flexibility for clinical programs and translational research. Trial Registration: NCT05413005.