Abstract
In less than a decade, the applications of virus-based therapeutics have significantly expanded and are no longer restricted to ultra-rare diseases. Viral vector production strategies must rapidly evolve to keep up with this increased demand for diversity and yield. Downstream purification processes are often a bottleneck during viral vector manufacturing. Challenges include a lack of standardization, low recovery, poor scalability, and maintaining quality standards.
Adhering to the principles of quality by design (QbD) is an effective risk management tool. Although its application to viral vector production processes is still in its infancy, the concepts can be broadly implemented to control and demonstrate quality throughout development and manufacturing.
This chapter provides a holistic overview of current downstream technologies used in purifying both lentiviral vectors (LVs) and adeno-associated viruses (AAVs), from the initial lysis step performed at harvest up to and including final sterile filtration. We also touch upon QbD principles in gene therapy and how early adoption of these strategies during process development can help the successful commercialization of new products.
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Cashen, P., McLaughlin, K. (2023). Overview of Current Downstream Processing for Modern Viral Vectors. In: Gautam, S., Chiramel, A.I., Pach, R. (eds) Bioprocess and Analytics Development for Virus-based Advanced Therapeutics and Medicinal Products (ATMPs). Springer, Cham. https://doi.org/10.1007/978-3-031-28489-2_5
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