HYBRID GPP-HOSPITAL CONTROL STRATEGY FOR SEMI-SOLID EXTRUSION 3D PRINTING OF ONC201 CHEWABLE UNITS IN PEDIATRIC ONCOLOGY.

Abstract

Children with central nervous system tumors often face significant barriers to age-appropriate medicines, especially when dysphagia prevents the use of conventional tablets or capsules. ONC201 (dordaviprone), a first-in-class imipridone available in France under a compassionate access program, poses additional challenges of poor solubility and chemical instability. Chewable formulations offer an attractive solution for pediatric compliance, but their development requires robust pharmaceutical and regulatory controls to ensure safety, stability, and reproducibility. We describe a hybrid GPP-hospital control strategy for semi-solid extrusion (SSE) three-dimensional printing of ONC201 chewable units. In this model, an ONC201 hydrogel intermediate is prepared centrally in a Good Preparation Practices (GPP)-compliant unit under Quality by Design (QbD) specifications and subsequently distributed to hospital pharmacies for on-demand personalization. Patient-ready chewable units are produced locally under in-process controls (IPCs) that monitor extrusion, geometry, unit weight, disintegration, and drug content. Formulation screening and batch characterization identified a stable ONC201 hydrogel suitable for decentralized use, with a conservative refrigerated shelf-life of 14 days. Printed chewable units demonstrated consistent quality attributes and rapid drug release, meeting pharmacopeial expectations for immediate release dosage forms. By combining centralized QbD-controlled preparation with decentralized hospital-based personalization, this work establishes a transferable framework for safe, traceable, and patient-adapted delivery of ONC201 in pediatric oncology, complementing ongoing clinical investigations.