Even in the absence of contamination, there is a risk of non-compliance with

regulatory guidelines, if the plan to mitigate virus-contamination risk is inadequate.

The risk of non-compliance can block license approval for specific markets with

significant commercial impact.

The contamination of a manufacturing facility can lead to substantial economic

losses during and after the incident, and can result in patient hardship as a con-

sequence of the loss or interruption of the drug supply [8].

An adventitious virus contamination during cell culture manufacture of a bio-

logic is incredibly disruptive [9]. Firstly, extensive efforts in time and resources

need to be allocated for the identification of the contaminant, the source of the

contamination and the extent of the contamination. These investigations can delay

the development of new products. Secondly, corrective actions, such as changes of

raw materials or decontamination of facilities, must be implemented. Finally, the

reputation of the manufacturer can be tarnished, and its competitive advantage can

be dented.

4.3.2

SOURCES OF VIRAL CONTAMINATIONS

Potential adventitious agents might be introduced into the process via three main

sources, illustrated in Figure 4.1:

Animal-derived

raw materials

Contaminated

raw materials

GMP-failure

Starting

materials

Cell bank

Virus seed

Cell culture

FIGURE 4.1 Three sources of viral contamination in biomanufacturing.

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Bioprocessing of Viral Vaccines