The interest for robust and scalable viral vector manufacturing is rapidly increasing, with the recent developments of both cell and gene therapy and oncolytic virus-based therapies. As cost pressure in the biopharma and vaccine industry increase globally, the choice of manufacturing technology is becoming increasingly important. The manufacturing processes and technologies are critical to enable cost-efficient and scalable production of safe and efficacious clinical-grade virus products. This week, Process Development Forum speaks with Dr. Mats Lundgren, customer applications director at GE Healthcare Life Sciences.
What are the main reasons for this rapid increase in viral vector manufacturing?
Viral vector platforms emerging at the crossroads of cell, gene therapy, and vaccines are becoming a promising area of growth. In the last couple of years, there have been several new approved therapeutics based on viral vectors and many more are in the development pipeline. This results in a large demand for viral vector production. Furthermore, there is also a shortage in available manufacturing capacity within many companies as well as in contract manufacturers.
What are the main challenges for viral vector manufacturing? Are there good solutions for virus propagation?
Viral vectors are viruses that are genetically modified to deliver specific genes or antigens. Viruses are large multiprotein complexes and in the case of vectors, they must also be infectious to be efficacious. Thus, viral vectors are often challenging to produce, especially at large scale. Viruses are produced by cell culture and the host cell line must be well characterized and the culture conditions has to be thoroughly optimized. Also, the cell culture medium and any supplements need to be of clinical grade quality. From a regulatory perspective, it is recommended to avoid any raw materials that are of animal origin such as serum and other components as these could potentially contain adventitious agents.
Is virus purification also challenging? Are platform solutions a realistic approach?
Yes, the purification process can be quite complex. Viruses are much larger than recombinant proteins and antibodies, and therefore tailored purification technologies must be used. The scalability factor must be considered as well. We strongly recommend the use of scalable technologies both for virus propagation as well as purification. For example, single-use bioreactors, filtration, and chromatography techniques are suitable for virus production.
Due to the diversity of viruses, platform solutions are challenging to implement especially for purification. However, as certain types of viruses such as Lentivirus for cell therapy and Adeno-Associated Virus for gene therapy become more common, there is a possibility for development of virus specific platforms.
How do plasmid manufacturing fit within this increased focus of gene therapy and vaccines?
In some cases, such as for Lentivirus and Adeno-Associated Virus, the virus can be produced upon introduction into the host cell line by transfection of plasmids encoding both the viral genes and the gene of interest. Thus, the plasmids are used as a raw material in the virus process and the quality is highly important. Plasmid production must therefore be carried out using the same type of processing as for biopharmaceuticals and vaccines. Also, in this case, it is critical to use scalable processing technologies that comply with regulatory requirements.
Do you have any other final advice?
An important aspect is the use of advanced analytics because this will help you to understand your process and characterize the product. Finally, consider the process economy early in development. It is important to do process economy modelling at relevant production scales to ensure the commercial viability of your product.
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