Peak Serum: Implications of Serum Supply for Cell Therapy Manufacturing

Serum-reduced and serum-free media for differentiation of Caco-2 cells

“…In 2008 the European Centre for Alternative Methods Scientific Advisory Committee issued a statement about the use of FBS and other animal-derived supplements, in favor of the use of specified synthetic supplements to satisfy both reproducibility and animal welfare ethics (http://ecvam.jrc.it/publication/ESAC28_statement_ FCS_20080508.pdf). 4) the fast growing cell therapy industry (CtI) is already facing the problem of limited availability of FBS; serum production and current serum stocks soon will be unable to support the CTI, and a significant raise in the price of good manufacturing practice-grade serum has already occurred in recent years (Brindley et al, 2012). The human intestinal Caco-2 cell line (Pinto et al, 1983) has been used extensively during the past 30 years as the best avail-1 Introduction 1 to maintain, propagate, and differentiate human and animal cells in vitro, the culture medium must be supplemented with serum, either of human or animal origin.…”

“…2) Composition of serum is still partially undefined and, more importantly, it can vary greatly from supplier to supplier and, within the same brand, from batch to batch (Rolleston, 1999). Such variability can affect cell culture conditions, ultimately causing uncontrolled variations in experimental results (Sambuy et al, 2005;Zucco et al, 2005;Brindley et al, 2012).…”

Fetal bovine serum (FBS): Past – present – future

“…It is calculated that approximately 8% of cows in the slaughter line are pregnant at different stages of gestation. Recent figures estimate that about 800,000 liters of FBS are produced annually worldwide, corresponding to 2,000,000 bovine fetuses, with numbers still increasing (Brindley et al, 2012).…”

“…The US Food and Drug Administration (FDA) has also indicated that the use of animals should be minimized and replacements utilized, including use of equivalent in vitro methods, when applicable (Brindley et al, 2012;Mannello and Tonti, 2007;Tekkatte et al, 2011). And, last but not least, for clinical-scale or Good Manufacturing Practice (GMP)-compliant manufacturing of cell-based products (advanced therapy medicinal products (ATMPs)) regulatory authorities request the replacement of FBS (EMA, 2011).…”

“…Owing to the questionable reproducibility of models that rely on FBS, their use for regulatory purposes is debated (Brindley et al, 2012;Mannello and Tonti, 2007;Tekkatte et al, 2011). For this reason, serum-supplemented media should be avoided wherever possible, and chemically-defined media preferred (see also Section 2, and van der Valk et al, 2010).…”