Process economical effects of implementation of ready-to-use micro carriers in cell- based virus vaccine production

Micro-carriers are used as support for the growth of adherent cells. By providing a large cultivation surface in bioreactor cultures, micro-carriers have replaced, to a great extent, cultivation in Cell Factory™ systems or roller bottles over the last decades. At Sanofi Pasteur, one of the world leaders in human vaccines, Cytodex™ 1 microcarriers have been used in the production of viral vaccines on Vero cells for several years. In accordance with the supplier’s recommendation, the microcarriers that are delivered dry are swollen in buffer, washed, and heat-sterilized before use. Since October 2016 a ready-to-use Cytodex™ 1 alternative, delivered presterilized by gamma irradiation, is available. Before implementing the change, the presterilized alternative was first evaluated with regards to reduced preparation time and cost. With a two-year shelf-life, the presterilized alternative reduced utility cost and added flexibility to operations by decreasing the need for steam and stainless steel materials in viral production facilities, and in alignment with extended use of single-use bioreactors equipment. The second step was to compare the cell growth and viral productivity using this ready-to-use alternative with that of the prior referenced product in place. Both cell growth and viral productivity were comparable between the two products, which supported further the documentation for the implementation of this ready-to-use alternative in GMP manufacturing for new R&D vaccine projects. The qualification process covered technical, quality, and analytical aspects based on the supplier documentation, and internal analyses and justification regarding our requirements in upstream vaccine production. While the presterilized Cytodex™ 1 microcarriers are now implemented in process development for new vaccines and qualified for manufacturing of clinical batches of new vaccine products, the next step will be to evaluate the benefits and impacts of replacing the microcarrier reference product with the gamma sterilized alternative on industrial products

Polymorphism of Plasmodium falciparum Na+/H+ exchanger is indicative of a low in vitro quinine susceptibility in isolates from Viet Nam

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>NA+/H+ exchanger (<it>pfnhe1</it>, gene PF13_0019) has recently been proposed to influence quinine (QN) susceptibility. However, its contribution to QN resistance seems to vary geographically depending on the genetic background of the parasites. Here, the role of this gene was investigated in <it>in vitro </it>QN susceptibility of isolates from Viet Nam.</p> <p>Method</p> <p>Ninety-eight isolates were obtained from three different regions of the Binh Phuoc and Dak Nong bordering Cambodia provinces during 2006-2008. Among these, 79 were identified as monoclonal infection and were genotyped at the microsatellite <it>pfnhe1 </it>ms4760 locus and <it>in vitro </it>QN sensitivity data were obtained for 51 isolates. Parasite growth was assessed in the field using the HRP2 immunodetection assay.</p> <p>Results</p> <p>Significant associations were found between polymorphisms at <it>pfnhe1 </it>microsatellite ms4760 and susceptibility to QN. Isolates with two or more DNNND exhibited much lower susceptibility to QN than those harbouring zero or one DNNND repeats (median IC₅₀of 682 nM <it>versus </it>median IC₅₀of 300 nM; <it>p </it>= 0.0146) while isolates with one NHNDNHNNDDD repeat presented significantly reduced QN susceptibility than those who had two (median IC₅₀of 704 nM <it>versus </it>median IC₅₀of 375 nM; p < 0.01). These QNR associated genotype features were mainly due to the over representation of profile 7 among isolates (76.5%). The majority of parasites had <it>pfcrt76T </it>and wild-type <it>pfmdr1 </it>(> 95%) thus preventing analysis of associations with these mutations. Interestingly, area with the highest median QN IC₅₀showed also the highest percentage of isolates carrying the <it>pfnhe1 </it>haplotype 7.</p> <p>Conclusions</p> <p>The haplotype 7 which is the typical Asian profile is likely well-adapted to high drug pressure in this area and may constitute a good genetic marker to evaluate the dissemination of QNR in this part of the world.</p

Synthesis of well-defined inorganic layers using fluidized bed

Thin nanocrystalline CeO2, ZrO2 or Ta2O5 films were deposited onto substrates. Their sintering behavior was characterized and compared with the known equivalent TiO2 special effect pigments in terms of grain size, grain growth and layer porosity. These oxide layers were then converted into Ce2S3, Zr2ON2 and Ta3N5 in a fluidized bed prototype controlling the reaction conditions. The use of this method leads to a drastic reduction of the time of conversion compared to a stationary oven or to a rotary kiln. The color travel of the resulting products was analyzed using the CIELAB system. The intensity of the interference color was correlated with the effective refractive indices of these films, which also depends on their porosity. Keywords: Oxide Layers, Sintering, Interference Color, Fluidized BedDes films nanocristallins, d'épaisseur contrôlée (50 à 200 nm), de CeO2, ZrO2 ou Ta2O5 ont été déposés par voie aqueuse sur des substrats. Leur frittage a été étudié et comparé à celui de pigments nacrés équivalents (TiO2) en terme de taille des grains, croissance granulaire et porosité. Ces oxydes ont été ensuite convertis en Ce2S3, Zr2ON2 et Ta3N5 dans un prototype de lit fluidisé en contrôlant les conditions de réaction. Cet appareil conduit à une réduction importante des temps de réaction compare s à ceux qui sont obtenus dans des fours stationnaires ou rotatifs. Lévolution de la couleur de ces produits a été analysée en utilisant le système CIELAB. Les intensités des couleurs dínterférence ont été corrélées aux valeurs des indices de réfraction effectifs des films, valeurs qui dépendent aussi de leur porosité.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Nonparametric level-set segmentation based on the minimization of the stochastic complexity

International audienceIn this paper, a novel non parametric method of image segmentation is deduced from the stochastic complexity principle. The main advantage of this approach is that it does not rely on any assumption on the probability density functions in each region and does not include any free parameter that has to be adjusted by the user in the optimized criterion. This results in a very flexible and robust segmentation algorithm. Various simulations performed with both synthetic and real images show that the proposed non parametric algorithm performs similarly to the parametric counterparts with the flexibility of a nonparametric approach

Rotations culturales et production bananière : destruction des bananeraies et implantation d'une culture fourragère

Une dégradation de la fertilité des sols dans les systèmes intensifs de monoculture bananière est observée actuellement aux Antilles françaises. Ce problème provient des replantations fréquentes et de la mécanisation des nombreuses opérations culturales. Les principaux facteurs de dégradation sont la destruction de la bananeraie qui précède sa replantation et la toxicité des nématocides appliqués pour contrôler les nématodes du bananier. Afin de résoudre ces problèmes, de nouveaux systèmes de culture ont été proposés par le CIRAD-FLHOR reposant sur l'assainissement des sols par des rotations culturales, l'utilisation de matériel végétal sain (vitroplants), l'amélioration des techniques de préparation des terres et la limitation des pratiques culturales susceptibles de dégrader la structure du sol. Ce rapport présente l'évaluation et la mise au point des nouveaux itinéraires techniques préconisés concernant la destruction des bananeraies à l'aide de rotobêches et l'implantation d'une culture de Bracharia en alternance avec le bananier, permettant d'éliminer les nématodes infeodés au bananier; Bracharia n'étant pas une plante hôte des nématodes du bananie

Sintering and color properties of nanocrystalline CeO2 films

Thin (d=60 nm/140 nm) nanocrystalline CeO2 films were deposited onto mica flakes. Their sintering behavior was characterized and compared with the known equivalent TiO2 special effect pigments in terms of grain size, grain growth and layer porosity. The color travel of the resulting products was analyzed using the CIELAB color metric. The intensity of the interference color was correlated with the effective refractive indices of these films, which also depend on their porosit

Sintering of nanocrystalline Ta2O5 and ZrO2 films compared to that of TiO2 films

Thin (d = 60 nm/140 nm) nanocrystalline Ta2O5 and ZrO2 films were deposited onto SiO2 flakes, using a liquid route synthesis. Their sintering behaviour was characterized and compared to that of the corresponding powders and the known equivalent TiO2 film in terms of grain size, grain growth and layer porosity. The effect of the substrate was noticeable on crystallisation process but not on grain growth. The sintering behaviour was actually dictated by the initial size and the packing of the precipitated grains related to the synthesis of the film