Introducing NanoFacT: A Platform for Efficient and Precise (Semi-) Continuous Nanomanufacturing

Introduction

Nanomedicines enhance solubility, bioavailability, and targeted delivery, which is crucial as ~40% of marketed drugs and ~90% of small-molecule candidates have poor aqueous solubility [1]. Their complexity, combined with limitations of batch manufacturing (poor size control, complex downstream processing, low throughput, batch to-batch variability, and high costs), hampers robust production. Continuous manufacturing (CM) offers improved control, real-time monitoring of critical quality attributes (CQAs) via process analytical technology (PAT), steady state operation, shorter production cycles, reduced carbon footprint, and lower bioburden [1-4]. Remaining process sensitivities can be mitigated using quality-by-design, robust PAT strategies, and model-based control.

Objective: This study focuses on (semi-)CM of nanomedicines, specifically: implementing continuous top-down and bottom-up lines, applying PAT for real-time quality monitoring, and developing PAT-enabled automation frameworks for efficient process design and control.

Methods

Results

• Solvent-free, temperature-controlled production of blank and drug-loaded lipid-based nanoparticles
• 5-fold higher throughput vs. batch by optimizing CMAs and CPPs
• Inline SR-DLS enabled real-time particle size monitoring and earlier instability detection than conventional DLS

• SR-DLS-based PAT-driven automation framework using realtime data to rapidly optimize settings, minimize operator intervention, and divert out-of-spec material
• AQbD-driven UPLC lipid quantitation method validated to ICH Q2 (R2) standards

Conclusion

• Combined top-down and bottom-up manufacturing platform for precise nanomedicine production
• Inline SR-DLS enables real-time size monitoring, supporting immediate process adjustments to maintain product quality
• Future integration of additional PAT tools and coupling with simulations, automation and data-driven workflows will expand the platform

See the full poster on Introducing NanoFacT here

(click the picture to download the poster)

Source: poster: Introducing NanoFacT: A Platform for Efficient and Precise (Semi-) Continuous Nanomanufacturing, C. Tetyczka, S. Celikovic, C. Glader, R. Jeitler, A. Azimi, J.A. Afonso Urich, Y. Wang, P. Caisse, S. Mesite, S. Stephan, V. Bourgeaux, M. Spoerk, J. Khinast, E. Roblegg, NanoFact, Gattefossé, KNAUER, Uni Graz, Skyepharma, Microfluids, InProcess LSP, RESEARCH CENTER PHARMACEUTICAL ENGINEERING