A risk-assessment model to rate the occurrence and relevance of adventitious agents in the production of influenza vaccines.

Influenza vaccine production has traditionally relied on the use of embryonated chicken eggs for virus isolation and propagation, but recently, cell-culture-derived manufacturing methods have been introduced. During influenza vaccine production, by either conventional or cell culture methods, there is a risk of incidental contamination by adventitious agents. Thus, a risk-assessment model has been developed to qualitatively assess the potential risk of vaccine process contamination by viral pathogens. The model takes into account the basic growth characteristics of each virus, its ability to grow in different cell substrates and resistance to processing steps during vaccine manufacture. The risk-assessment model has been applied to various pathogens to determine potential risk and relevance in different manufacturing scenarios, using different cell substrates for virus propagation, including Madin-Darby canine kidney (MDCK) cells. Avian viruses, introduced via use of embryonated eggs for virus isolation, were found to present the greatest risk, irrespective of the substrate used for influenza virus propagation. The use of MDCK cells to propagate vaccine virus from egg-isolated influenza virus strains does not introduce a new or greater adventitious virus risk, compared with egg-based vaccine production. Indeed, the adventitious virus risk is potentially reduced as fewer viruses are able to grow in MDCK cells.