Opinion on adventitious agents testing for vaccines: Why do we worry so much about adventitious agents in vaccines?

• Testing for adventitious agents in viral vaccines is at a turning point.
• Historical methods are being called into question, particularly in vivo methods.
• New methods are on the horizon.
• The traditional strategy of just continuing to add new tests as they emerge is not consistent with Quality by Design principles.
• A rational, science-derived and risk-based path forward is proffered.

The manner in which viral vaccines are produced in a biological system makes them vulnerable to microbial contamination. Considerable effort is expended to avoid such contamination and to detect it if it occurred. Is this effort warranted, efficient, scientifically sound, and rational? When asked for my opinion on these matters, I agreed to discuss the basis and historical context for why we do what we do and proffer opinion on what we might do instead or in addition, as we look forward to the inclusion of new strategies and methods in our arsenal. Being an advocate of the 3 R's policy, I invite a re-examination of the traditional in vivo methods in particular. I also advocate for a risk-based approach consistent with “Quality by Design” as a more scientific and rational means of addressing these issues. In the end, vaccinologists need to reassure the public that the vaccines they or their children receive are safe and pure and that all reasonable measures are taken to safeguard them.