A Risk-Based, Qtpp-Driven Framework For Semi-Solid Extrusion 3d Printing of Personalized Medicines: Integrating...

Area of Science:

• Pharmaceutical Sciences
• Biomedical Engineering
• Regulatory Science

Background:

• Semi-solid extrusion (SSE) 3D printing offers potential for personalized oral medicines.
• Current regulatory pathways for SSE 3D printing are fragmented, hindering widespread adoption.
• Hospital compounding and early-phase clinical trials have distinct but related regulatory needs.

Purpose of the Study:

• To develop an applied, risk-based regulatory framework for SSE 3D printing of pharmaceuticals.
• To integrate hospital compounding and clinical trial regulatory models using the concept of printable ink as a pharmaceutical intermediate.
• To support reproducible, traceable, and flexible production of personalized medicines across decentralized manufacturing sites.

Main Methods:

• Developed a framework using quality-by-design principles (ICH Q8-Q11, USP <1220>).
• Defined critical quality attributes (CQAs), critical process parameters (CPPs), and in-process controls (IPCs).
• Stratified active pharmaceutical ingredients (APIs) by risk and mapped them to quality control strategies using empirical data from pediatric use cases.

Main Results:

• A unified regulatory model was established for centralized and point-of-care SSE 3D printing.
• Two tables were created to guide risk-based decisions on quality control strategies (IPCs vs. full GMP).
• The framework demonstrated applicability across diverse APIs and pediatric use cases, including trimethoprim-sulfamethoxazole, cyclophosphamide, tamoxifen, and isoleucine.

Conclusions:

• The harmonized model addresses regulatory ambiguity in SSE 3D printing.
• It enables science-based decisions for quality control, ensuring safety and efficacy.
• The framework supports innovation in pediatric and rare disease medicine while ensuring reproducible and traceable pharmaceutical production.