Risk Level 1, no animal/human cell-based starting materials are used in the man-

ufacture of the vaccine. Vaccines in this category are prepared from bacteria and

yeast. The major source of virus contamination comes from animal-derived raw

material used to prepare the culture media. But any minor virus contamination

cannot propagate in such a cell substrate.

Risk Level 0, no primary animal-derived materials and no starting materials are

used in the manufacture of the vaccine. Any minor virus contamination present or

occurring during manufacture cannot be amplified in the absence of cell substrate.

Nucleic acids-based vaccines are in this category.

4.3.4

CASE STUDY: THE PCV1/ROTARIX INCIDENT

The discovery of a previously undetected contaminant in a licensed biological

medicinal product occurs typically through the application of new analytical

technologies, often with improved sensitivities or capabilities not previously

available [11]. The porcine circovirus example is illustrative. Porcine circovirus

(PCV1) sequences were detected in Rotarix by the group of Eric Delwart in 2010

using next-generation sequencing [12]. GlaxoSmithKline (GSK) initiated extensive

investigation to identify that the source of the PCV1 contamination was most likely

the porcine trypsin, used in 1983 to prepare the Vero MCB [13]. PCV1 had not been

detected in conventional tests for more than 20 years, and therefore was able to

propagate in the Vero cell substrate without being detected [14].

One week after the detection of PCV1 in Rotarix (15 March 2010), the FDA

recommended that clinicians and public health professionals in the United States

Highly purified

No viral growth

Risk Control

Inactivated

Live attenuated

Nucleic acids

+++

++

+

+++

++

+

FIGURE 4.2 Viral safety risk and control for different vaccine types.

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Bioprocessing of Viral Vaccines