MilliporeSigma

Viral Vector Vaccine Manufacturing

Process Train for Viral Vector Vaccines

Fig 1. Process Train for Viral Vector Vaccines

A live vector vaccine uses an attenuated or harmless microorganism such as an adenovirus to transport portions of an antigen to stimulate an immune response. Vectored vaccines are capable of inducing potent cell-mediated immunity, which is essential for complex disease like AIDS, malaria, and cancer among others.

While the manufacturing process for vaccine vectors is fairly templated, some challenges may arise, since several different viruses with varying properties can be used. For large viral vectors, process sterility is critical due to yield loss associated with sterile filtration. There are also challenges with vector aggregation and stability.

In addition, many Phase I/II processes involve adherent cell cultures; as a result, scaling to Phase III and commercial manufacturing can require process adjustments to achieve production targets. In later phases, product yield and purity are critical, as high dosage titers are required in the final product.


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Accelerate time to clinical while ensuring reliable scale-up

Upstream culture processes developed for manufacturing of viral vector vaccines must be optimized to meet productivity requirements. This optimization includes the cell lysis and clarification steps which are essential for removal of cells and cell debris and to ensure a robust vector harvest. The upstream process is only successful, however, if it can be reliably scaled in order to meet anticipated market demand.

Achieve yield and efficiency goals with robust impurity removal

Nucleic acids from lysed cells are a common contaminant in viral vector vaccine processes. Regulations require that the level of carry-over host cell nucleic acid be below 10 ng/dose of attenuated viral vaccine. Benzonase® endonuclease treatment followed by tangential flow filtration is a robust and powerful combination to degrade and remove residual nucleic acid components.

Maximize downstream recovery

Small-scale clinical lots are typically purified using CsCl-based density gradient ultracentrifugation, while large-scale production requires a two- or three-step chromatography process. Anion exchange is typically used to remove HCP, DNA, RNA, and other major contaminants, while size exclusion chromatography is used for trace contaminant removal.

Ensure Patient Safety

Sterile filtration ensures the sterility of the final formulated product and patient safety. A filter pore size of 0.22 µm or less is required to eliminate microbial contaminants. A key consideration for the sterile filtration process is the level of viral aggregates. These aggregates need to be controlled by optimizing the formulation, otherwise, the sterile filtration process will be challenging with the potential for high losses in yield.


Upstream Cell Culture

Upstream Cell Culture

Streamline and optimize upstream workflows for maximized efficiency and production of viral vectors.

    Nuclease Treatment & Clarification
    Downstream - Tangential Flow Filtration
    Downstream Chromatography
    Downstream Process Chemicals and Formulation
    Bioprocessing Liquid Cell Culture Media & Buffers

    We offer the industry’s highest quality sterile filtered liquid capabilities, supplying ready-to-use cell culture media, buffers, CIP and SIP products from GMP facilities worldwide to optimize your biopharma production.

    Final Sterile Filtration & Filling

    Ensure patient safety with a reliable and robust sterile filtration process.

    ·         Final Sterile Filtration & Filling

    ·         Sterile Filtration Strategies

    ·         Sterile Sampling with Novaseptum® Go Sterile Sampling Solutions

    ·         Fill-Finish with Mobius® Single-Use Fill-Finish solutions

      Validation & Testing Services





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