Fernanda Fonseca

How Vial Geometry Variability Influences Heat Transfer and Product Temperature During Freeze-Drying

Vial design features can play a significant role in heat transfer between the shelf and the product and, consequently, in the final quality of the freeze-dried product. Our objective was to investigate the impact of the variability of some geometrical dimensions of a set of tubing vials commonly used for pharmaceuticals production on the distribution of the vial heat transfer coefficients (Kv) and its potential consequence on product temperature. Sublimation tests were carried out using pure water and 8 combinations of chamber pressure (4-50 Pa) and shelf temperature (-40°C and 0°C) in 2 freeze-dryers. Kv values were individually determined for 100 vials located in the center of the shelf. Vial bottom curvature depth and contact area between the vial and the shelf were carefully measured for 120 vials and these data were used to calculate Kv distribution due to variability in vial geometry. At low pressures commonly used for sensitive products (below 10 Pa), the vial-shelf contact area appeared crucial for explaining Kv heterogeneity and was found to generate, in our study, a product temperature distribution of approximately 2°C during sublimation. Our approach provides quantitative guidelines for defining vial geometry tolerance specifications and product temperature safety margins.

Interactive evolutionary modelling of living complex food systems: freeze-drying of lactic acid bacteria

Modelling the production and stabilisation process of lactic acid starters has several practical applications, ranging from assessing the efficacy of new industrial methods, to proposing alternative sustainable systems of food production. In order to reach this objective, however, it is necessary to overcome several obstacles, tied to the complex nature and interactions of the target processes. In this paper, we present a novel complex system modelling approach, exploiting both stand-alone evolutionary search and visual interaction with the user. The presented framework is then tested on a real-world case study, for which it shows promising results.

LIDeOGraM: An Interactive Evolutionary Modelling Tool

Building complex models from available data is a challenge in many domains, and in particular in food science. Numerical data are often not enough structured, or simply not enough to elucidate complex structures: human choices have thus a major impact at various levels. LIDeOGraM is an interactive modelling framework adapted to cases where numerical data and expert knowledge have to be combined for building an efficient model. Exploiting both stand-alone evolutionary search and visual interaction with the user, the proposed methodology aims at obtaining an accurate global model for the system, balancing expert knowledge with information automatically extracted from available data. The presented framework is tested on a real-world case study from food science: the production and stabilisation of lactic acid bacteria, which has several important practical applications, ranging from assessing the efficacy of new industrial methods, to proposing alternative sustainable systems of food production.

Draft Genome Sequence of Lactobacillus delbrueckii subsp. bulgaricus CFL1, a Lactic Acid Bacterium Isolated from French Handcrafted Fermented Milk

ABSTRACT Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) is a lactic acid bacterium widely used for the production of yogurt and cheeses. Here, we report the genome sequence of L. bulgaricus CFL1 to improve our knowledge on its stress-induced damages following production and end-use processes.

Effect of freeze-dryer design on heat transfer variability investigated using a 3D mathematical model

During the freeze-drying process, vials located at the border of the shelf usually present higher heat flow rates that result in higher product temperatures than vials in the center. This phenomenon, referred to as edge vial effect, can lead to product quality variability within the same batch of vials and between batches at different scales. Our objective was to investigate the effect of various freeze dryer design features on heat transfer variability. A 3D mathematical model previously developed in COMSOL Multiphysics and experimentally validated was used to simulate the heat transfer of a set of vials located at the edge and in the center of the shelf. The design features considered included the vials loading configurations, the thermal characteristics, and some relevant dimensions of the drying chamber geometry. The presence of the rail in the loading configuration and the value of the shelf emissivity strongly impacted the heat flow rates received by the vials. Conversely, the heat transfer was not significantly influenced by modifications of the thermal conductivity of the rail, the emissivity of the walls, or the geometry of the drying chamber. The model developed turned out to be a powerful tool for cycle development and scale-up.

Determination of the dried product resistance variability and its influence on the product temperature in pharmaceutical freeze-drying

Graphical abstract Figure. No caption available. Abstract During the primary drying step of the freeze‐drying process, mass transfer resistance strongly affects the product temperature, and consequently the final product quality. The main objective of this study was to evaluate the variability of the mass transfer resistance resulting from the dried product layer (Symbol) in a manufacturing batch of vials, and its potential effect on the product temperature, from data obtained in a pilot scale freeze‐dryer. Sublimation experiments were run at −25 °C and 10 Pa using two different freezing protocols: with spontaneous or controlled ice nucleation. Five repetitions of each condition were performed. Global (pressure rise test) and local (gravimetric) methods were applied as complementary approaches to estimate Symbol. The global method allowed to assess variability of the evolution of Symbol with the dried layer thickness between different experiments whereas the local method informed about Symbol variability at a fixed time within the vial batch. A product temperature variability of approximately ±4.4 °C was defined for a product dried layer thickness of 5 mm. The present approach can be used to estimate the risk of failure of the process due to mass transfer variability when designing freeze‐drying cycle. Symbol. No caption available.

Subcellular membrane fluidity of Lactobacillus delbrueckii subsp. bulgaricus under cold and osmotic stress

Cryopreservation of lactic acid bacteria may lead to undesirable cell death and functionality losses. The membrane is the first target for cell injury and plays a key role in bacterial cryotolerance. This work aimed at investigating at a subcellular resolution the membrane fluidity of two populations of Lactobacillus delbrueckii subsp. bulgaricus when subjected to cold and osmotic stresses associated to freezing. Cells were cultivated at 42xa0°C in mild whey medium, and they were exposed to sucrose solutions of different osmolarities (300 and 1800xa0mOsm L−1) after harvest. Synchrotron fluorescence microscopy was used to measure membrane fluidity of cells labeled with the cytoplasmic membrane probe 1-[4 (trimethylamino) phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). Images were acquired at 25 and 0xa0°C, and more than a thousand cells were individually analyzed. Results revealed that a bacterial population characterized by high membrane fluidity and a homogeneous distribution of fluidity values appeared to be positively related to freeze-thaw resistance. Furthermore, rigid domains with different anisotropy values were observed and the occurrence of these domains was more important in the freeze-sensitive bacterial population. The freeze-sensitive cells exhibited a broadening of existing highly rigid lipid domains with osmotic stress. The enlargement of domains might be ascribed to the interaction of sucrose with membrane phospholipids, leading to membrane disorganization and cell degradation.