While FCS is treated as having almost universal application, chemically-defined media are cell-type specific, meaning that for every cell type used a new medium needs to be developed. One significant challenge in developing chemically-defined media as alternatives to FCS is the sheer number of cell types in use – almost 120,000 according to the Cellosaurus database (as of July 2020). This is also a big challenge for the FCS-Free Database, but we have succeeded in bringing attention to this issue and creating an effective way for researchers to find and share information on alternatives.

To avoid the use of FCS in the short term when no defined medium is available, human platelet lysates (hPLs) could be considered as a supplement, particularly when working with human cells. hPLs are produced from expired donated human blood, contain many growth factors, and seem to have universal application. Still, as a biological product, they also differ from batch to batch.

The development of a defined medium for a specific cell type may seem a tedious exercise, but appropriate experimental design via the use of a design matrix can allow for multiple components to be varied within the same experiment. This not only shortens the development time, but also takes factor interactions into account. A crucial step that should not be ignored is the adaptation of cells to the new medium. Although its role is not fully understood – whether cells really adapt or sub-cloning occurs – it seems crucial for most cells to thrive in the new medium.