1. Raw materials of animal origin might carry extraneous agents of bovine,

porcine, human or other origins (e.g. porcine trypsin, foetal bovine serum,

or human serum albumin). Other raw materials can be also contaminated

by contact with animals.

2. Starting materials including cell banks and virus seeds might contain

extraneous agents introduced during their preparation and the amplification

of such materials in different culture conditions (presence of animal de-

rived material) or on different cell substrates (e.g., in the process of virus

attenuation).

3. Manufacturing operations might bring viral contaminations from various

sources:

a. Environmental contaminants might be introduced via contaminated

equipment and air. These contaminants are primarily agents that are very

stable and have endured prolonged periods in a dry or liquid environ-

ments, which do not support growth of the contaminating agent.

b. Contamination by human operators might occur if viruses/agents

from the respiratory tract or from contaminated body surfaces are

introduced into process material during open-air operations such as the

preparation of culture media.

According to Onions et al. [10], the majority of contamination problems in the bio-

technology and vaccine industry have a root cause associated with an adventitious

agent in a raw material. In a review of viral contamination cases [9] three of the four

viruses (blue tongue virus, CacheValley virus, and vesivirus 2117) that contaminated

CHO cell cultures were suspected or identified as having come from serum. However,

and by contrast, the minute virus of mice (MVM) was found to have contaminated a

process in which no animal-derived material had been used [9].

4.3.3

LEVELS OF RISK

Biologics, including vaccines, can be categorized according to their viral-risk level

and the capacity to mitigate this risk. These risks are detailed below and described

in Figure 4.2.

Risk Level 3, all three main sources of contamination are combined. Most vaccines

produced from animal/human cell cultures are in this category. When the vaccines

are from inactivated viruses, mitigation protocols in the manufacturing process can

be used to reduce the risk. For the other live-attenuated vaccines, for which the

purification is often limited or absent, the control is dependent on precautionary

measures taken during the selection of the raw materials and during the entire

manufacturing process. The risk also can be mitigated by implementing additional

testing when a potential virus contaminant is highlighted by the risk assessment.

Risk Level 2, no primary animal-derived raw material is used during the manu-

facturing of the vaccine, which is also highly purified. However, the vaccines in this

category are prepared from cell banks and seeds. Hence, the viral risk is still

present.

Cell lines for vaccine production

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