Organelles

Analyzing the
Business and Technology
of Stem Cells

Born Free? Stem Cell Researchers Saying
"No Thanks"

March 13, 2013

An upcoming report from the International Society for Cellular Therapy (ISCT) looks set to provide some discouraging news for would-be vendors of specialty cell culture media to the stem cell therapeutics industry.

At a November meeting of officials from the FDA’s Center for Biologics Evaluation and Research with 20+ cell therapy stakeholder organizations (the 12th Cell Therapy/FDA Liaison Meeting), EMD Millipore’s Knut Niss, chairman of ISCT’s Process and Product Development Committee, outlined the results of ISCT’s not-yet-published Survey on MSC Production Methods. The survey queried senior-level investigators worldwide who work with human mesenchymal stem cells (MSCs), 79% of whom produce their own cells in-house. Niss reported that the survey found a surprisingly small fraction of respondents – just 4% – use serum-free media to culture their cells, while the vast majority (76%) use media supplemented with human or animal blood products such as fetal calf serum (FCS) or platelet lysate.

Cell culturists have long employed ‘crude’ media supplements, such as FCS, to provide their growing cells with unidentified factors promoting vigorous cell growth in vitro. But with the rise of cell therapies, the use of such unrefined animal- or human-origin manufacturing components has raised increasing concern regarding their potential to transmit infectious agents (such as that causing bovine spongiform encephalopathy, or ‘mad cow disease’) or immunogenic molecules to cell therapy products, with consequences for patients that, arguably, could be disastrous.

How real this threat may be is open to debate, but its possibility has encouraged a number of companies – including SCSI component, StemCells, Inc. (STEM), as well as competitors such as Lonza, Life Technologies, BD, and others – to market ‘serum-free’ stem cell expansion media supplemented with individual identified growth factors (often recombinant in origin, and thus also ‘animal-free’). Marketing these today as ‘Research Use Only’ products, such vendors hope that steadily growing adoption of serum-free and/or animal-free media by researchers – a fairly small market opportunity – will ultimately lead to later adoption in the cell therapy manufacturing market, where the huge media volumes required could translate into very substantial revenues for serum-free/animal-free media vendors.

Unfortunately for these vendors, adoption of serum-free/animal-free media has been painfully slow, and dishearteningly thin: the ISCT survey’s finding that just 4% of researchers currently use serum-free media to grow MSCs reveals for the first time just how dismal the situation really is. With the first such commercial medium (Life Technology’s STEMPRO® MSC SFM) now five years old, 4% market penetration for serum-free media today is nothing short of a disaster.

Why such low adoption? After all, avoiding injecting patients with random cow parts seems like something of a no-brainer. Several factors are probably at play. First, serum-free/animal-free media are much more expensive, liter for liter, than conventional serum-containing media. In this era of steadily declining research budegets, investigators naturally avoid costly new technologies unless they are mission-critical…which serum-free media aren’t perceived to be. A second factor is simple inertia – a researcher who has been growing MSCs in serum-containing media for the past decade or more is naturally loathe to court the potential for unintended consequences that a sudden recipe change might present. Yet another factor is the FDA itself, which has so far declined to take a strong position requiring the use of serum- and/or animal-free media in cell therapy manufacturing. Lastly, a good share of the blame must be laid at the feet of the media vendors themselves, whose frequently half-hearted and too-often ineffective marketing efforts have failed to educate researchers to the important fact that many types of stem cells (and particularly MSCs) grow much more rapidly, with much higher yields, in the best serum-free media formulations than they do in conventional serum-containing media (no one really knows why).

The details of pharmaceutical manufacturing processes get ‘locked-in’ at the start of Phase 3 clinical trials, frequently never to change again. With the vast majority of U.S. stem cell trials now in Phase 2 (see our Clinical Trials page), now is the time for serum-free/animal-free media vendors to make their best case to cell therapy developers…but the ISCT survey’s results suggest that isn’t happening. The consequences of this for media vendors’ bottom lines is one thing, but the potential impact on the safety of tomorrow’s stem cell therapies is quite another.

Our conversations with leaders throughout the stem cell therapeutics industry indicate a wide range of attitudes toward the question of adopting serum- and/or animal-free media in their future production protocols. A very few have already succeeded. A larger number have tried to develop their own proprietary serum- and animal-free media (in response to the perhaps misperceived high cost of commercial offerings), with distinctly mixed results. The development of high-performance serum-free cell culture media is not a task for the faint of heart (I know; some years ago I led the team that developed and delivered to market what is perhaps the best-performing formulation available today). But the vast majority of stem cell therapy developers merely express the intention to get serious about the problem Real Soon Now (i.e., they have no real plans). One hopes this latter group, along with an overly complacent FDA and disheartened media vendors, aren't just whistling past the graveyard.