Full Title: De-bottlenecking Challenges in Large Scale Viral Vector Manufacturing for Gene Therapy Applications
The rush to develop an affordable and accessible COVID-19 vaccine not only accelerated research and development of therapeutic modalities like viral vector, mRNA and pDNA based vaccines but also challenged the bioprocess community to solve for unique scale-up related challenges to manufacture these important life-saving medicines.
Adenoviral vectors are attractive vectors for delivering genes for other gene therapy applications. These vectors can accommodate large transgenes, transduce quiescent and dividing cells, and do not integrate into the host’s genome. Adenoviral vector technology using HEK293 host cells has been around for a long time and the manufacturing process includes upstream processing (HEK293 cell culture and viral infection), followed by series of clarification, filtration, and chromatography steps to produce drug substance with high purity. Although, the process unit operations seem uncomplicated, manufacturing at large scale in single use systems has remained a major challenge due to poor and inconsistent cell growth in suspension culture during scale-up, low viral titers, product aggregation, inefficient separation of empty and filled viral capsids, as well as complexities related to handling large volume viral infection. Hence, there is a strong requirement to build robustness and scalability in early process development to minimize unnecessary late-stage process changes, as well as design cGMP facility and strong quality culture to handle operational complexities and reduce risks associated with viral vector manufacturing. The webinar will illustrate key questions and challenges in large -scale manufacturing of viral vectors from a process robustness, facility design and product quality standpoint as well as our experiences in debottlenecking these challenges to scale adenoviral vector technology at 2000L and beyond.