product stability. The ultimate goal of the development of DSP is to reach a final

manufacturing process that is in accordance with the guidelines of the regulatory

authorities for full-scale production of the biotherapeutic target into the market. The

following chapter will cover the different operation units, from the harvest of the

product from cell culture until the sterile filtration to formulate the final product.

Besides a well designed purification process, there is the need for good analytical

tools and quality control in parallel, so this topic will be also briefly discussed in

this chapter, focusing on the importance of high throughput process development.

In the end, the future of purification technology will be also highlighted regarding

topics as new facility design and process intensification.

7.1.1

VIRAL-BASED VACCINES MANUFACTURING––CURRENT CHALLENGES

IN DOWNSTREAM PROCESSING

For viral-based vaccines (VBVs), the downstream processing is a challenging task. It

involves the purification of high amounts of complex particles assembled from proteins,

lipids, and nucleic acids thanks to the combination of several validated purification

procedures. Moreover, the biological complexity and diversity of the viral-based pro-

ducts can directly impact the selected purification process schemes. For example, lower

amounts of host cell DNA and host cell protein (HCP) are present in enveloped viral

vector’s production systems than for non-enveloped viruses. However, such enveloped

viruses are more sensitive to shear stress; thus, achieving high yields of purified viral

products is more challenging (Figure 7.1). All these factors have to be taken into ac-

count during process development, while decreasing the cost per dose.

As DSP can account for up to 60–70% of the overall production cost, its opti-

mization will extensively contribute to more cost-effective processes There have

been great achievements in the implementation of robust vaccine manufacturing

processes using animal cells to increasing viral product titer and quality. However,

much less effort has been put to the essential downstream processing. Thus, this

constitutes currently a major bottleneck together with the development of dedicated

analytical tools. Moreover, the growing pressure to develop cost-efficient processes

has brought the need to improve purification strategies, when compared with the

traditional purification methods, that will be discussed later in this chapter.

FIGURE 7.1 Comparison (pros and cons) between enveloped and non-enveloped viral vectors.

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Bioprocessing of Viral Vaccines