Abstract

Process Analytics for Nanotherapeutics Manufacturing, Enabled by Novel Inline Nanoparticle Sizing Technology

Rut Besseling, Scientific Director, InProcess Instruments BV

The rise of nanotherapeutics -and nano based products in general- has increased  the need for better characterization, understanding and control of nano-particle (NP) suspensions in synthesis and processing. In Pharma this is emphasized by regulatory drives for Quality by Design (QbD) and process monitoring via Process Analytical Technology (PAT). But continuous measurement of NPs like LNPs or liposomes using PAT integrated in the production process, has so far hardly been possible. Specifically, NP size characteristics -critical for endproduct quality- could previously not be measured inline due to the challenges regarding e.g. suspension turbidity and ‘agitation’ for standard methods (e.g. standard Dynamic Light Scattering, DLS). This has been an important barrier in successful development, scale-up and manufacturing of nanotherapeutics. Here I will describe applications of a new non-invasive PAT instrument – the NanoFlowSizer (NFS)- providing continuous, real-time, in-process size characterization of NP suspensions, over a vast range of suspension turbidities and flow conditions. The NFS resolves scattered light signals as function of depth in the suspension (‘Spatially Resolved Dynamic Light Scattering’), which provides the key solution to the turbidity/flow challenges mentioned for inline NP sizing. After a brief technology intro, several examples are described highlighting the NFS’ novel process monitoring capabilities. These include monitoring of solid NP syntheses (SiO2/TiO2/Ibuprofen), pharmaceutical nano-emulsion homogenization, processing of protein solutions and, lastly, continuous manufacturing of liposome formulations, including unique PAT-based automated process control for ‘on target’ production.