New unique PAT method and instrument for real-time inline size characterization of concentrated, flowing nanosuspensions

Quality by Design for enabling RNA platform production processes

“…Relatively simple real-time particle size analyzers, such as those based on inline or online dynamic light scattering (DLS) methods, are implementable for both the LNP formation and purification steps [90]. A combination of multiangle light scattering, UV and refractive index detectors, coupled with size exclusion chromatography, is able to measure sizedependent RNA content in less than 1 h [91].…”

A state of the art in analytical quality-by-design and perspectives in characterization of nano-enabled medicinal products

“…Nearinfrared spectroscopy-in-line, Raman in-line, chemical imaging, particle imaging and measurement, solid state nuclear magnetic resonance, powder X-ray diffraction or tetrahertz pulsed imaging are all examples of PAT implemented in the pharmaceutical industry. Some emerging PAT addressing nanomaterial specific properties are technologies for online sizing, such as spatially resolved dynamic light scattering (SR-DLS) provided by the NanoFlowSizer [32] (for more details see Section 5).…”

“…Consequently, it is impossible to fine-tune the processing parameters in real time during the manufacturing phase. Some emerging technologies for online sizing are currently being tested, such as spatially resolved dynamic light scattering (SR-DLS) provided by the NanoFlowSizer [32], or real time multiangle light scattering (RT-MALS) [61], which are able to characterize the size and molecular weight of turbid nano dispersions, enabling PAT analysis of the physical properties of nanomaterials. Both technologies have been tested on lipid based nanoparticles, polymeric particles and liposomes with very promising results, ensuring batch consistency by online monitoring for size of the entire batch or immediate discharge of the product if the particle size no longer meets specification.…”

A Quality by Design Approach in Pharmaceutical Development of Non-Viral Vectors with a Focus on miRNA

“…In order to fulfill the ICH and QbD requirements for manufacturing of robust nanoparticles formulations, real-time monitorization using PAT instruments is needed [ 70 , 71 ]. Currently, a PAT instrument is implemented for nanoemulations and nanosuspensions manufacturing for real-time size and size distribution monitorization [ 72 ]. This noninvasive and continuous measurement of nanoparticles’ physical characteristics reduces waste, minimizes batch rejects, and reduces production cycling time.…”