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Process development for successful gene therapies

To successfully manufacture gene therapy and viral vaccine products – your process needs to be cGMP-ready by design. From the very beginning, our main focus is to achieve a robust and reliable large-scale manufacturing process. At the same time the approach must be flexible enough to allow protocol optimization for different phases, as we continuously assay quality, adjust critical parameters and manage risk.

To successfully manufacture gene therapy and viral vaccine products – your process needs to be cGMP-ready by design. From the very beginning, our main focus is to achieve a robust and reliable large-scale manufacturing process.

Process development involves several challenges, including problems with scale-up, cost-efficiency, product quality – and then assessing that quality with fast and reliable assays. We have faced these challenges many times with several clients, and – together – we always came out winners.

It all starts with choosing the right combination of a high quality host/virus system. A choice that will mainly depend on the system’s ability to effectively produce the target product, but safety and toxicity needs to be taken into account as well.

Viral vectors

Our team of experts have long experience in working with multiple viruses and virus vectors, including:

  • Adenovirus
  • Adeno-associated virus (AAV)
  • Lentivirus
  • Poxvirus
  • Baculovirus

Host cell platforms for upstream development

Selecting the right host cell is critical, because different host cells have different capabilities and different growth properties, including their suitability for growth in adherent vs suspension cultures.

  • HK-293 can serve as excellent plasmids to make AAV virus and are used for production of lentiviruses. Typically, in suspension processes.
  • C6 human cell line are often used for propagation on Influenza A and B.
  • Sf9/Sf21 are well-established hosts with regulatory traction.
  • CHO are well-established, characterized and proven hosts with great versatility.
  • EB66 are mainly used for antibody production.
  • Vero have regulatory traction with an approved product, but are not compatible with suspension processes which may present some manufacturing challenges.
  • MDCK have good virus growth advantage and adapt well to serum free media.

Viral Gene Therapy expression systems

Vaccine expression systems

FUJIFILM Diosynth Biotechnologies is a global leader in viral gene therapies development and production. We use a wide variety of vaccine expression systems based on mammalian expression as well as microbial fermentation.

Gene therapies

Purification strategies and downstream process

Purification strategies are important to consider early on in process development to ensure long term success. In fact, the highest costs often arise in downstream processing because of loss of yield, quality assurance etc.

Normally, downstream purification involves at least a clarification step, an ultra-filtration step, chromatography steps to capture and refine the product, and virus inactivation steps for safety purposes.

But there is really no generic solution to purification, because different vectors present different purification challenges. A deep understanding of the properties of the specific vector is critical, because characteristics like stability and isoelectric point will determine the optimal parameters and conditions. To minimize the number of steps in the purification of your specific biopharmaceutical and achieve maximum yield, you will need an experienced team. We can be your partner.

Experience have taught us a few guiding principles. For example that virus purification by ultracentrifugation is typically not a scalable solution. And that purification by chromatography should be considered very early in process development. But more than anything, experience has taught us that process development in gene therapy and vaccine production is a craftmanship that is very specific for each host/virus system and requires experience.