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Master Thesis

Développement et optimisation de procédé de production d’anticorps monoclonaux en cellules CHO

Abstract : Developing a new drug is a high-risk investment for a company as only one lead out of 10,000 molecules is marketed and its development is long and expensive: around 12 years and 1 Billion Euro. In addition, the increasing requirements from authorities during trials prior giving market authorisation, the time limited-patent and the emergence of biosimilar are all challenges to be addressed by companies developing new biological entities. Drug development combines preclinical and clinical trials with process development. Process development is performed after the cell line development and engineering step. This thesis focuses on subsequent process development: particularly on process optimisation, fine-tuning and scale-up, which are followed by characterisation and validation for commercial manufacturing. The four case studies were selected to present different aspects of both cell culture and clarification development in the context of a company developing new biological entities, particularly monoclonal antibodies. Examples of cell culture process development are broached but at different stages. It shows the importance of fine-tuning a cell culture process to reach a 2L scale-down model which is suitable for the fine-tuning of the control strategy of a large scale GMP process. A molecule process development can also start facing short deadlines: the strategy will be to optimise the process directly at 80L scale using a platform process Critical optimisation checkpoints are the feeding strategy and the process scalability assessment (scale comparison between 10L and 80L) which are needed for implementing the process at GMP scale. The primary recovery process has become a critical step as high cell density and high producing cultures are more challenging to clarify and harvest directly impacts both product yield and quality. Developing and optimising these operations can include selecting alternative filters for a process but also enhancing centrifugation & filtration performance of another process by adding a treatment to the final culture broth prior to harvesting it. Quality by design places the quality attributes of the therapeutic molecule at the center of the development. All design of experiment and decisions have been made in regards to the impact on product quality. Platform production and QbD are both holistic and systematic approaches which enabled achieving in a short time robust results and improvements of the processes in a competitive environment where pressure on cost and timelines is always greater.
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Master Thesis
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Contributor : Bu Carreire Université de Bordeaux <>
Submitted on : Wednesday, December 7, 2016 - 3:39:58 PM
Last modification on : Wednesday, August 23, 2017 - 4:31:08 PM
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  • HAL Id : dumas-01411559, version 1



Margaux Vigata. Développement et optimisation de procédé de production d’anticorps monoclonaux en cellules CHO. Sciences pharmaceutiques. 2016. ⟨dumas-01411559⟩



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