To lead clinical trials, it is crucial to industrialize the production of innovative treatments to provide clinicians with viral vectors in quantity and quality. This requires the development of robust manufacturing and quality control processes, collectively referred to as bioproduction.
Our commitment: To produce gene therapy treatments at reduced costs through innovative manufacturing, analysis, and control processes.
Genethon’s bioprocess development team designs, scales and characterizes production and analysis procedures for viral vectors. These methods are then transferred to our pharmaceutical-grade production partner, Yposkesi, which produces the batches used in Genethon’s clinical trials.
The team is also tasked with developing technological innovations to enhance the performance and robustness of vector production processes, both in terms of productivity (increasing yields and reducing costs) and the quality of the manufactured products.
Our strength: More than forty collaborators work on developing and improving manufacturing processes for these gene therapy products. This begins with the design of vector sequences, optimization of cell culture and transfection conditions (upstream process), and the development of purification, concentration, and formulation processes (downstream process) for viral vectors. The challenge is to facilitate and ensure the reliable transition from laboratory scale to industrial scale, which is particularly complex.
Bioproduction: An Integrated and Multidisciplinary Approach
Vector Design and Optimization of Expression Systems
The production of viral vectors is preceded by the design and manufacture of plasmids that carry the therapeutic gene expression cassette as well as the sequences necessary for viral vector formation.
The Vector Innovation and Production System team designs and generates plasmid constructs to produce viral vectors for various Genethon projects and its partners. This team also explores innovative technologies and new production systems to improve the productivity and quality of vectors.
Cell Culture, Purification, and Formulation
- Vectors (AAV or lentiviral) are currently produced by cells cultured in suspension, allowing control over the scale-up required during development and robust large-scale production. Production processes are initially developed in shaken flasks, then transferred to scalable bioreactors to ultimately enable industrial-scale production (bioreactors ranging from 2L to 200L).
- Once the vectors are produced by the cultured cells, the downstream process enables them to be harvested, then purified to eliminate all impurities and contaminants from the cells and/or the used process, then concentrated and formulated.
Analysis and Characterizationation
The entire bioproduction chain (from vector design to their formulation) requires the development and application of precise, rapid, sensitive, and robust analytical methods, in accordance with current regulatory requirements for pharmaceutical product development.
Innovation: The Driver of Our Performance
Genethon has had to innovate to produce these complex drugs. Over the past 20 years, Genethon has developed numerous production and analysis methods for gene therapy drugs.
This innovation approach is at the heart of our activity and continues either internally or through external collaborations with academic laboratories, technology providers, as well as pharmaceutical and biotech industries.
These advances have made it possible to design manufacturing processes for nearly 15 treatments and ensure their transfer to pharmaceutical production, benefiting patients.
All these innovations now make it possible to produce treatments for clinical trials that require large quantities of vectors, particularly for neuromuscular diseases such as Duchenne muscular dystrophy.
Pharmaceutical Production: Yposkesi
Founded in 2016 by Généthon, AFM-Téléthon, ISTEM, and BPI France, Yposkesi is now one of Europe’s leading CDMOs for pharmaceutical-grade (GMP) viral vector production. In 2021, the entry of the SK Pharmteco group into its capital strengthened its industrial capacities to meet the growing global demand for vector production for gene therapy treatments.
