Mixing of Monoclonal Antibody Formulated Drug Substance Solutions in Square Disposable Vessels.

Fill & finish manufacturing processes of biologics drug product involve multiple unit operations. In particular they often include a mixing step to reduce non-uniformities in fluids by eliminating gradients of concentration and pH may occur during freezing. This step should be conducted carefully to avoid any degradation of the protein under mechanical stress. This study was aimed at characterizing disposable vessels of square cross-section such as Levmixer® from Sartorius Stedim in terms of fluid dynamics and mixing in turbulent regime. The investigation included two tree large vessels (50, 200 & 650-l) and one 4-l vessel designed in house. For that purpose, the impact of stirrer speed, filling volume and duration of mixing on product quality attributes were studied, using a surrogate. Moreover, a scale-up rule, based on first principle, was established and allows prediction of the mixing time as a function of stirring speed and filling volume. A lab-scale test, using drug product, was performed at the same stress intensity but for a much longer duration than the commercial operation and did not reveal any trend to aggregation. Finally, based on the correlation, lab scale stress test and a single verification test at large scale, a design space within which the product can be processed without altering product quality was proposed.

Droplet Microfluidics for Food and Nutrition Applications.

Droplet microfluidics revolutionizes the way experiments and analyses are conducted in many fields of science, based on decades of basic research. Applied sciences are also impacted, opening new perspectives on how we look at complex matter. In particular, food and nutritional sciences still have many research questions unsolved, and conventional laboratory methods are not always suitable to answer them. In this review, we present how microfluidics have been used in these fields to produce and investigate various droplet-based systems, namely simple and double emulsions, microgels, microparticles, and microcapsules with food-grade compositions. We show that droplet microfluidic devices enable unprecedented control over their production and properties, and can be integrated in lab-on-chip platforms for in situ and time-resolved analyses. This approach is illustrated for on-chip measurements of droplet interfacial properties, droplet-droplet coalescence, phase behavior of biopolymer mixtures, and reaction kinetics related to food digestion and nutrient absorption. As a perspective, we present promising developments in the adjacent fields of biochemistry and microbiology, as well as advanced microfluidics-analytical instrument coupling, all of which could be applied to solve research questions at the interface of food and nutritional sciences.