Vaccines are one of the most effective public health medicinal products with an excellent
safety record. As vaccines are produced using biological materials, there is a need
to safeguard against potential contamination with adventitious agents. Adventitious
agents could be inadvertently introduced into a vaccine through starting materials
used for production. Therefore, extensive testing has been recommended at specific
stages of vaccine manufacture to demonstrate the absence of adventitious agents. Additionally,
the incorporation of viral clearance steps in the manufacturing process can aid in
reducing the risk of adventitious agent contamination. However, for live viral vaccines,
aside from possible purification of the virus or vector, extensive adventitious agent
clearance may not be feasible. In the event that an adventitious agent is detected
in a vaccine, it is important to determine its origin, evaluate its potential for
human infection and pathology, and discern which batches of vaccine may have been
affected in order to take risk mitigation action. To achieve this, it is necessary
to have archived samples of the vaccine and ancillary components, ideally from developmental
through to current batches, as well as samples of the biological materials used in
the manufacture of the vaccine, since these are the most likely sources of an adventitious
agent. The need for formal guidance on such vaccine sample archiving has been recognized
but not fulfilled. We summarize in this paper several prior major cases of vaccine
contamination with adventitious agents and provide points for consideration on sample
archiving of live recombinant viral vector vaccines for use in humans.