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Gene therapy process change evaluation framework: Transient transfection and stable producer cell line comparison

Comisel, R-M; Kara, B; Fiesser, FH; Farid, SS; (2021) Gene therapy process change evaluation framework: Transient transfection and stable producer cell line comparison. Biochemical Engineering Journal , 176 , Article 108202. 10.1016/j.bej.2021.108202. Green open access

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Abstract

As the gene therapy sector grows, decisions related to the best time to switch from the typical transient transfection expression system to more reproducible and scalable stable producer cell line (SPCL) systems have garnered much interest. This paper describes the application of a decisional tool to identify the most attractive expression system and optimal timing for the process change for four hypothetical gene therapy products based on either lentiviral (LV) or adeno-associated virus (AAV) vectors using suspension culture processes. The tool comprised models to analyse the cost of goods, cost of drug development, project lifecycle cost and profitability to evaluate the major trade-offs such as the reliance on costly plasmid DNA supply with transient transfection versus the longer cell line development times with SPCL. The tool predicted that switching to SPCL early in development, with no delay to market, was the most attractive strategy from cost of drug development and project lifecycle cost perspectives for products requiring larger quantities of viral vector. If this scenario resulted in a 10-month delay to market, then the optimal solution from a profitability perspective changed to switching to SPCL post-approval or sticking with transient transfection. Scenario analyses were performed to identify critical thresholds for the plasmid DNA costs, delays to market and SPCL harvest titre values that affect the rankings of the strategies.

Type: Article
Title: Gene therapy process change evaluation framework: Transient transfection and stable producer cell line comparison
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bej.2021.108202
Publisher version: https://doi.org/10.1016/j.bej.2021.108202
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Technology, Biotechnology & Applied Microbiology, Engineering, Chemical, Engineering, Transient transfection and stable producer cell line, Lentiviral and adeno-associated virus vectors, Plasmid DNA, Autologous CAR T-cell and haematopoietic stem cell gene therapy, ex vivo and in vivo gene therapy, Cost of goods, RECOMBINANT ADENOASSOCIATED VIRUS, PERFUSION CULTURE PROCESSES, DECISION-SUPPORT TOOL, LENTIVIRAL VECTOR, T-CELLS, BIOPROCESS ECONOMICS, CLINICAL DEVELOPMENT, STRATEGIES, IMMUNODEFICIENCY, PURIFICATION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10137727
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