A Guide to Viral Vector Manufacturing

Keywords: Viral vector manufacturing, Viral vector CDMO, Gene Therapy, Viral vector production.

Viral vector manufacturing is on track to skyrocket more than 27% in the next five years. Viral vectors have exciting potential: they play a key role in new cell therapies, gene therapies, and vaccines. They are also proving useful in producing anticancer agents. That being said, bringing a viral vector treatment onto the market is challenging. Indeed, the correct design of the viral vector project is crucial and many parameters need to be taken into account when doing so. In this article, learn more about viral vector manufacturing and how the right manufacturing partner can help accelerate your time to market.

How to Choose the Vector: LV or AAV

Viral vectors are viruses engineered to deliver genetic material into cells. Viral vectors are ideal delivery vehicles. They can target and enter specific cells very efficiently. A viral vector can use the target cell’s ability to produce a therapeutic agent.

Integrating and Non-Integrating Vectors

Gene therapy viral vector production relies on two main categories of vectors:

• Lentivirus (LV), which is an integrating viral vector;
• Adeno-associated virus (AAV), which is a non-integrating vector.

Integrating viral vectors integrate into the genome of the target cell. They replicate in daughter cells after mitosis. This provides for stable genetic alteration in dividing cells. Non-integrating viral vectors remain episomal. They enable persistent transgene expression in cells that don’t proliferate.

cGMP Viral Vector Manufacturing

Either category of vectors can meet current Good Manufacturing Practice (cGMP) standards. Compliance with FDA cGMP regulations is essential for pharmaceutical manufacturing. It is part of the drug approval process and manufacturers must prove they can safely produce the product. cGMP rules cover the requirements for manufacturing, processing, and packing drug products. They include manufacturing methods, facilities, and controls.

What Is cGMP LV Production?

Lentivirus is one of the most frequently used integrating viral vectors. LV gene therapy from viral vector production is already in use (numerous approved treatments and ongoing clinical trials). A typical LV manufacturing workflow starts with plasmid development and production. Then, upstream processes include cell expansion and plasmid transfection and viral vector production from the transfected host cells. After that, the downstream segment of the manufacturing workflow first purifies the viral particles and the last stage in the process is the fill and finish of the final product. Adherent or suspension systems are suitable options for LV manufacturing.

What Is cGMP AAV Production?

Adeno-associated virus is a common choice for a non-integrating vector. It has a good safety profile. Infection with the vector isn’t pathogenic. It can’t replicate on its own and doesn’t directly integrate into the host genome. cGMP AAV production follows the same basic steps as LV production, and AAV can be produced in adherent or suspension systems. Developing a stable producer line allows manufacturing scale up more efficiently.

How to Choose the Cell Expansion System

The two cell expansion systems for viral vector manufacturing are adherent and suspension. They both allow for ex vivo and in vivo therapies.

Adherent

Adherent cell culture grows cells while they’re attached to a substrate as monolayers. The advantages of adherent cell culture are that cell maintenance and production are straightforward in the early development stages and scaling up production can move quickly. One of the drawbacks is that scaling up can require significant equipment and space and an adherent system can be more expensive.

Suspension

Suspension cell cultures leave the cells floating freely in the culture medium. The advantages of the suspension systems are that a suspension process is more straightforward to operate than an adherent process; a stirred-tank bioreactor may be a good option as it makes scaling up production simpler and the cost of consumables is lower than for adherent expansion.

The Importance of the Cell Line

The producer cell line is the foundation of viral vector therapy. Choosing the right host cell line early in development is essential. A defined, well-developed cell line minimizes variation between batches.
Features to consider include:

• Origin and derivation;
• Doubling time;
• Permissiveness for viral infection and replication;

The cell line needs to be robust enough to withstand upstream processing. To meet cGMP requirements, it must have a documented history. It must pass tests for purity and safety.

Read our article regarding our new HEK293 cell line.

Challenges of Viral Vector Manufacturing

Viral vectors have great potential but working with them is challenging. Some of the challenges include:

• Handling the complexities of working with viral particles and living cells;
• High capital costs for establishing and maintaining production facilities;
• Scaling up manufacturing;
• Gaps in process engineering;
• Managing strict storage and logistics requirements;
• Complying with rigorous safety regulations.

Many viral vector therapeutics never reach commercial production, or many pharmaceutical companies discover that their process isn’t scalable or cost-effective enough. This type of failure can result in losing billions of dollars and years of research, and this is why working with an experienced CDMO can be a suitable solution for pharmaceutical companies.

Viral Vector Manufacturing CDMO

Pharmaceutical developers need to reduce the costs and risks of viral vector manufacturing. Contract manufacturing and development organizations (CDMOs) are a solution. CDMOs manufacture the final product but they can also handle the development process. Using a CDMO benefits pharmaceutical companies in several ways:

Lower Infrastructure Costs

A CDMO can help bring new products to market without pharmaceutical companies having the need to invest in more infrastructure. A viral vector CDMO, such as Yposkesi, has the specialized equipment, expertise, and facilities for viral vector manufacturing.

Use Specialized Expertise

A viral vector CDMO has experts with specialized skills for research, development, and production. Being specialized, the CDMO also has experience and expertise in the viral vector manufacturing process. Hence, pharmaceutical companies can reduce their payroll costs while benefiting from expert staff.

Scaling Production

A CDMO can adapt to changing production volumes as needed. Indeed, production volume can scale up or down to meet demand and adding product variations is also possible. Pharmaceutical companies that use CDMOs can change production capacity more rapidly, hence they avoid the increased expenses of labour and facilities for in-house production.

Comply with cGMP Regulations

Using viral vector manufacturing CDMO streamlines the process of complying with cGMP regulations. The viral vector CDMO will ensure that the cell line will be expanded under cGMP conditions and can generate cell banks that are cGMP compliant. Used for Adenovirus or certain vaccines, a master virus seed stock will also be robust, traceable, and compliant with regulations. Starting with a cell line suitable for cGMP accelerates development. Hence, clinical trials can begin more quickly.

Viral Vector Manufacturing with Yposkesi

Viral vector manufacturing with a CDMO has many advantages for pharmaceutical companies. This specialized manufacturing can give your project an increased likelihood of success.

Yposkesi is one of the largest CDMOs in Europe for cell and gene therapy viral vector production. We offer a full range of LV and AAV manufacturing that meets cGMP standards. We’ll help ensure that your project has the right vector, expansion system, and cell line in order to help patients faster.

Contact us today to learn more about how we can support your project!