Imagine you have just designed and built a new car. Everyone loves it. It’s sleek, fast, elegant, has plenty of cup holders. People want to buy it. The only problem is you haven’t built an assembly line to make enough of them to meet demand. Frustrating eh.
Overcoming problems in manufacturing is not an issue that just affects the auto industry (which won’t make Elon Musk and Tesla feel any better) it’s something that affects many other areas too – including the field of regenerative medicine. After all, what good is it developing a treatment for a deadly disease if you can’t make enough of the therapy to help the people who need it the most, the patients.
As the number of stem cell therapies entering clinical trials increases, so too does the demand for large numbers of high quality, rigorously tested stem cells. And because each of those therapies is unique, that places a lot of pressure on existing manufacturing facilities to meet the demand.
So, with that in mind CIRM teamed up with the International Alliance for Biological Standardization (IABS) to hold the 4th Cell Therapy Conference: Manufacturing and Testing of Pluripotent Stem Cells to try and identify the key problems and chart out solutions.
The conference brought together everyone who had a stake in this issue, including leading experts in cell manufacturing, commercial sponsors developing stem cell treatments, academic researchers, the World Health Organization, the US Food and Drug Administration (FDA), international regulatory bodies as well as patient and patient advocates too (after all, who has a greater stake in this).
Commercial sponsors and academic researchers presented case studies of how they worked through the development of manufacturing process for their stem cell treatments.
Some key points quickly emerged:
- Scale up and quality control of stem cell manufacturing is vital to the development of stem cell treatments.
- California is a world leader in stem cell manufacturing.
- There have been numerous innovations in cell manufacturing that serve to support quality, quantity, performance and cost control.
- The collective experience of the field is leading to standardization of definitions (so we all use the same language), standardization of processes to release quality cells, manufacturing and standardization of testing (so we all meet the same safety requirements).
- Building consensus among stakeholders is important for accelerating stem cell treatments to patients.
Regulatory experts emphasized the importance of thinking about manufacturing early on in the research and product development phase, so that you can avoid problems in later stages.
There were no easy answers to many of the questions posed, but there was agreement on the importance of developing a stem cell glossary, a common set of terms and definitions that we can all use. There was also agreement on the key topics that need to continue to be highlighted such as safety testing, compatibility, early locking-in of quality processes when feasible, and scaling up.
In the past our big concern was developing the therapies. Now we have to worry about being able to manufacture enough of the cells to meet demand. That’s progress.
A technical summary is being developed and we will announce when it is available.
One thought on “Overcoming one of the biggest challenges in stem cell research”
Years from now (hopefully not too many!) other scientists will look back on now and ask, “What were they thinking to ignore the fundamental flaws in iPSCs as stem cell therapeutics?!” This incredulity will apply to differentiated cells produced from iPSCs, as well as iPSCs per se. How and why do current scientists who are driving the iPSC manufacturing agenda ignore well known genetic and epigenetic principles? Mutations that are inherent and frequent in iPSCs (as well as other artificial pluripotent stem cell types) will be inherited by the differentiated cells derived from them. This is an inherent fatal flaw for regenerative medicine therapies and drug development based on the use iPSC-derived cell types. In addition, successful durable stem cell cures require asymmetrically self-renewing and tissue cell-replenishing adult tissue stem cells. Ignoring these fundamentals is a futile exercise for patients, though the act might produce short-term profits for some. Eventually, for success in regenerative medicine, we must get back to intensifying research and development with naturally occurring adult tissue stem cells. Want to help more patients sooner? Get busy working on biological strategies that are not fundamentally and inherently flawed.