Process Development for Advanced Therapies

Scalable Gene Therapy processes

Developing a long-term manufacturing ready process for Gene Therapy and Viral Vaccine products can be a challenge. These challenges include selecting the right combination of Host/virus systems.

The use of viruses to produce important therapies including gene therapies have become an important modality in the treatment of many disorders. Selecting the right combination will depend mainly on safety, toxicity, and the ability of the host/virus combination to effectively produce the target product.

TYPICAL VIRAL VECTORS INCLUDE:
  • Adenovirus
  • Adeno-associated virus (AAV)
  • Lentivirus
  • Poxvirus
  • Baculovirus

Host cells have different growth properties, including adherent versus suspension cultures. This may require the evaluation of alternate platforms such as Hyperstacks™, Cell Factory™ systems and/or microcarriers. Some host cells, such as HEK, may have media requirements that can be challenging.

TYPICAL HOST CELL PLATFORMS HOSTS ARE:
  • HK-293-  these cells typically serve as excellent plasmids to make AAV virus. Also used in the production of lentiviruses.  Typically are compatible with suspension processes.
  • Per.C6- human cell line, characterized for the propagation on Influenza A and B.
  • Sf9/Sf21- well established systems with regulatory traction.
  • CHO- well proven, characterized, and established host.
  • EB66- typically used for antibody production.
  • Vero- these systems already have regulatory traction with an approved product. Manufacturing challenges as typically are not compatible with suspension processes.
  • MDCK- typically have good virus growth advantage, adapt well to serum free media.

Purification strategies for long term success are important to consider while developing a process. Ultracentrifugation for virus purification is typically not a scalable solution long term. Evaluation of purification by chromatography should be considered early during process development.