Pr\u00e9sentation de la plateforme BioFactory
\nAbdelkader Selmi,\u00a0Responsable de la plateforme BioFactory, CPE Lyon
\nBioFactory est la plateforme de CPE Lyon pour la Recherche, le D\u00e9veloppement et l\u2019Innovation en bioproduction et biotechnologies. Disposant d\u2019une cha\u00eene de bioproduction moderne et innovante \u00e0 l\u2019\u00e9chelle laboratoire, BioFactory a pour mission de former, accompagner et innover. BioFactory participe \u00e0 la formation continue (collaborateurs) et initiale (\u00e9tudiants) aux biotechnologies et \u00e0 la bioproduction. BioFactory accompagne les entreprises de secteurs divers (agro-alimentaire, bio\u00e9nergie, pharmaceutique\u2026) pour le d\u00e9veloppement, l\u2019optimisation et le scale-up de bioproc\u00e9d\u00e9s upstream (en bior\u00e9acteurs autoclavables ou \u00e0 usage unique) ou downstream. BioFactory propose une gamme de services adapt\u00e9s\u00a0: formation, conseil, r\u00e9alisation de projets R&D, fablab (mise \u00e0 disposition de nos \u00e9quipements pour vos collaborateurs).<\/p>\n
Conception optimale de bior\u00e9acteurs de culture de cellules souches mesenchymateuses humaines,\u00a0
\nEric Olmos,\u00a0Professeur\u00a0ENSAIA- LRGP Nancy
\nR\u00e9sum\u00e9
\nLes proc\u00e9d\u00e9s de culture de cellules souches m\u00e9senchymateuses en bior\u00e9acteur agit\u00e9 reposent sur l\u2019utilisation de microporteurs. Ces supports d\u2019adh\u00e9rence doivent \u00eatre mis en suspension par une agitation suffisante. Celle-ci doit \u00eatre un compromis entre une agitation trop faible qui pourrait induire des ph\u00e9nom\u00e8nes de friction inter-particulaires et une agitation trop forte qui intensifierait les contraintes hydrom\u00e9caniques et les collisions entre particules, avec des effets n\u00e9gatifs sur la quantit\u00e9 et la qualit\u00e9 de cellules produites. Au cours de cette pr\u00e9sentation, une approche couplant exp\u00e9rience et mod\u00e9lisation par CFD sera pr\u00e9sent\u00e9e. Cette approche, bas\u00e9e sur des simulations num\u00e9riques et des algorithmiques g\u00e9n\u00e9tiques d\u2019optimisation ont conduit \u00e0 la conception de syst\u00e8mes d\u2019agitation optimis\u00e9s et adapt\u00e9s \u00e0 la culture de CSM de cordons ombilicaux.
\nCes activit\u00e9s de recherche s\u2019inscrivent dans le projet ANR STEMCREATOR (205-2019) et dans le projet Europ\u00e9en INTERREG Improve-Stem (2017-2020).
\nR\u00e9f\u00e9rences
\nLoubi\u00e8re, C., Delafosse, A., Guedon, E., Chevalot, I., Toye, D., & Olmos, E. (2019). Dimensional analysis and CFD simulations of microcarrier\u2019just-suspended\u2019state in Mesenchymal Stromal Cells bioreactors. Chemical Engineering Science. Sous presse,\u00a0https:\/\/doi.org\/10.1016\/j.ces.2019.04.001
\nDelafosse, A., Loubi\u00e8re, C., Calvo, S., Toye, D., & Olmos, E. (2018). Solid-liquid suspension of microcarriers in stirred tank bioreactor\u2013Experimental and numerical analysis. Chemical Engineering Science, 180, 52-63.
\nMartin, C., Olmos, E., Collignon, M. L., De Isla, N., Blanchard, F., Chevalot, I., \u2026 & Guedon, E. (2017). Revisiting MSC expansion from critical quality attributes to critical culture process parameters. Process Biochemistry, 59, 231-243.
\nOlmos, E., Loubiere, K., Martin, C., Delaplace, G., & Marc, A. (2015). Critical agitation for microcarrier suspension in orbital shaken bioreactors: Experimental study and dimensional analysis. Chemical Engineering Science, 122, 545-554.
\nA propos de l\u2019intervenant
\nEric Olmos, Professeur en G\u00e9nie des bior\u00e9acteurs \u00e0 l\u2019ENSAIA, Responsable du Master G\u00e9nie des proc\u00e9d\u00e9s biotechnologies BioIn, Chercheur au Laboratoire R\u00e9actions et G\u00e9nie des Proc\u00e9d\u00e9s, \u00e9quipe Bioproc\u00e9d\u00e9s Biomol\u00e9cules. Eric Olmos r\u00e9alise ses activit\u00e9s de recherche sur le couplage entre les ph\u00e9nom\u00e8nes de transport (agitation, transferts gazeux) en bior\u00e9acteur et les performances du bioproc\u00e9d\u00e9. Les proc\u00e9d\u00e9s \u00e9tudi\u00e9s sont les proc\u00e9d\u00e9s de culture de cellules animales (lign\u00e9es continues CHO, cellules souches m\u00e9senchymateuses de cordons ombilicaux et de moelle osseuse), de culture de microorganismes (Streptomyces, Corynebacterium glutamicum) et les proc\u00e9d\u00e9s de m\u00e9thanisation.<\/p>\n
Suivi en ligne de nouveaux inhibiteurs m\u00e9taboliques par spectroscopie raman pour les proc\u00e9d\u00e9s culture de cellules CHO
\nEmma Petiot, Enseignant-Chercheur CPE Lyon
\nR\u00e9sum\u00e9 (ENG)
\nPROJET Collaboratif PFIZER St Louis, USA
\nConventional feeding control strategies employ fixed volume semi-continuous feeding and concentrated feed media. They are commonly unable to respond to exact nutrient consumption demands from the cultures resulting in accumulation of metabolite by-products and depletion of strategic nutrients. In order to develop the next generation of fed-batch processes, predictive feeding models have to be developed integrating the real culture needs. This involves the implementation of new process analytical technologies (PAT) allowing collecting data directly inside the cell culture processes. Few technologies are available to monitor concentrations of metabolites within the bioreactor cultures and Raman spectroscopy is one of them. Additionally, novel growth inhibitors derived from the partial metabolism of amino acids were recently identified for MAb CHO cell cultures [1]. To further optimize these culture performance and increase productivity, the real-time monitoring of such inhibitors and their connected amino acids would be a strategic step towards next generation Mab feeding-strategy production process.
\nThree amino acids and three metabolic inhibitors were targeted for in-line Raman monitoring. First, off-line calibrations for each target metabolites were built thanks to 154 samples of three fed-batch bioreactor cultures of CHO cells. This calibration set included clarified and non-clarified culture samples spiked with target concentration of metabolites of interest thanks to a designed specific DOE protocol in order to obtain an optimal calibration set with de-correlated metabolites concentrations. Then, validation set was built with 47 additional samples from 2 supplementary bioreactor cultures. Satisfactory R2 & Q2 > 0.7 were obtained for calibration of the two metabolic inhibitors and two of the amino acids. Calibration (RMSEC), cross-validation (RMSECV) and prediction errors (RMSEP) were found to be always below 1.5mM representing 15% of the concentration range occurring in the culture.<\/p>\n
Mulukutla BC, Kale J, Kalomeris T, Jacobs M, Hiller GW. Identification and control of novel growth inhibitors in fed-batch cultures of Chinese hamster ovary cells. Biotechnol Bioeng. 2017;114: 1779\u20131790. doi:10.1002\/bit.26313<\/p>\n
Single-use mixing solutions for large-scale media and buffer preparations and downstream unit operations
\nMyriam Lavie, Global Product Manager for Fluid Management Technologies at Sartorius Stedim Biotech, Aubagne, France
\nR\u00e9sum\u00e9 (ENG)
\nSingle-use mixing systems are increasingly used in the manufacture of biopharmaceutical products as they offer improved mixing performances, extended functionalities, such as disposable sensors, and operational benefits. Single-use mixing systems have been widely adopted for buffer and media preparation and are now finding\u00a0 applications in more critical and higher value unit operations in the downstream purification process steps.
\nThis case study will address the challenges currently met when implementing large volume single-use mixing systems for the preparation of buffers and media solutions, for which strong mixing forces are required for rapid and efficient powder dissolution.
\nFor the downstream unit operations where high-value purified products are processed, single-use mixing systems will raise additional needs such as low shear stress, in-line monitoring of process parameters and ultra-clean particulate free mixing conditions.
\nThis presentation focuses on case studies using large volume single-use mixing technology. Scalability of buffer and media preparations from 50L to 2,500L is first demonstrated using a magnetically-driven mixing technology. A simulation of a low pH virus inactivation is then presented using a contactless levitated impeller technology and a single use pH sensor. Finally, an example of final formulation is discussed with the re-suspension of a vaccine adjuvant.
\nA propos de l\u2019intervenante (ENG)<\/p>\n
Myriam Lavie\u00a0stands as Global Product Manager for Fluid Management Technologies at Sartorius Stedim Biotech, Aubagne, France
\nMyriam is in charge of the single-use mixers product range. She has more than 10 years of experience in engineering and marketing in the Biopharmaceutical industries and has been involved in many industrial projects for design, implementation and validation of single-use systems.
\nMyriam started her career in 2005 as a Process Engineer with GlaxoSmithKline Biologicals, Belgium. In 2007, she joined Sartorius Stedim Biotech as a Process Development Engineer for Fluid Management Technologies.
\nMyriam is a Process Engineer graduated from the \u201cEcole des Mines\u201d of Albi, France.<\/p>\n
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Pr\u00e9sentation de la plateforme BioFactory Abdelkader Selmi,\u00a0Responsable de la plateforme BioFactory, CPE Lyon BioFactory est la plateforme de CPE Lyon pour la Recherche, le D\u00e9veloppement et l\u2019Innovation en bioproduction et biotechnologies. Disposant d\u2019une cha\u00eene de bioproduction moderne et innovante \u00e0 l\u2019\u00e9chelle laboratoire, BioFactory a pour mission de former, accompagner et innover. BioFactory participe \u00e0 la […]<\/p>\n","protected":false},"author":1,"featured_media":194,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[9,13],"tags":[],"class_list":["post-143","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-conferences","category-evenements"],"acf":[],"_links":{"self":[{"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/posts\/143","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/comments?post=143"}],"version-history":[{"count":4,"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/posts\/143\/revisions"}],"predecessor-version":[{"id":300,"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/posts\/143\/revisions\/300"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/media\/194"}],"wp:attachment":[{"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/media?parent=143"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/categories?post=143"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biofactory.cpe.fr\/en\/wp-json\/wp\/v2\/tags?post=143"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}