Development of serum-free media for cell growth and production of viruses/viral vaccines--safety issues of animal products used in serum-free media.

The development of media free of serum and animal or human proteins is of utmost importance for increasing the safety of biological produced for therapy and vaccination. The main drawback associated with the use of serum or animal-derived substances for animal cell technology is the potential introduction of contaminants and, in particular, adventitious agents into the process and thus potentially also into the final product. This fact led to an increased effort to replace serum-containing by serum-free media. In most cases, these media are supplemented with purified proteins, peptones, or hydrolysates, mainly of animal or human origin. Although such serum-free media are more defined than serum-containing media, the risk of the introduction of viruses by using animal-derived substances is still present, signifying that only a complete replacement of animal-derived substances by non-animal-derived products leads to a relatively safe serum-free medium. In several examples the potential of serum-free media and media free of any animal-derived component in supporting growth of cell lines of interest for virus production (such as Vero or MDCK) and production of viruses, and, in particular, of influenza virus for vaccine production, are presented and discussed with respect to the classical production processes.