Comparing Adherent-Cell Technologies: Amplification of Virus Stocks and Viral Vectors

FUJIFILM Diosynth Biotechnology (FDB) is a multifunctional commercial development manufacturing organization (CDMO) that manufactures virus-based therapeutics. Its site in Texas specializes in both adherent and suspension cell culture for production of virus vectors and for development of analytical assays to support production and expression of our clients’ therapeutics. We work with a number of cell lines such as human embryonic kidney (HEK293) and human retinal cells (Johnson & Johnson/Crucell’s proprietary PER.C6 line), which can grow in suspension. However, many of the cell lines we work with do not grow well in suspension and thus are difficult to work with at large scale.

When a client approaches us to develop a process for manufacturing a vaccine or viral-based gene therapy, we first evaluate the cell line that has been used to grow the virus or viral vector. Few cell lines are suspension adapted and able to take advantage of the smooth scale-up process from shake flasks or spinner flasks into bioreactors. Suspension cultures grown in bioreactors allow for tight control of cell nutrients and parameters such as dissolved oxygen (DO), as well as sampling for easy monitoring.

Many viruses selectively grow in polarized cells and take advantage of that polarization for transport in and out of those cells. Such viruses often are difficult to produce in suspension culture. Thus, there is a need for a system that can support adherent cultures and be scaled up easily for manufacturing viral vaccines and vectors. Below, we describe case studies in three adherent cell growth systems and offer an overview of some analytical methods we can use to characterize viral products.

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