Last week, we finished our Ask the Expert Discussion on Clinical Stem Cell Manufacturing. There are an increasing number of promising new stem cell therapy candidates in development and many are showing promising results in clinical studies. As more stem cell therapies move from the lab to the clinical setting, there is increased interest in identifying best practices for stem cell manufacturing. Many researchers have specific questions about scaling up stem cell production, optimizing culture media, selecting the right manufacturing equipment, and the regulatory requirements for clinical production. These were the topics covered during our Ask the Expert session “Clinical Stem Cell Manufacturing.”

The session was hosted by Ronnda Bartel, Ph.D., Chief Scientific Officer, Aastrom Biosciences. Aastrom has successfully moved stem cell therapies from lab scale to clinical manufacturing and we were fortunate to have Ronnda’s expertise for this Ask the Expert session. Ronnda joined Aastrom in 2006 and is responsible for the scientific direction of the company, including research, development and technical operations. She has more than 20 years of research and product development experience and most recently was executive director, biological research at MicroIslet and vice president, scientific development at StemCells Inc.

Question topics included:

• Clinical stem cell manufacturing advancements
• Serum-free/animal-free media for stem cell manufacturing
• Autologous vs. allogeneic stem cell therapies
• Transitioning stem cells from the lab to the clinic
• Role of the pharmacist in the administration of stem cell therapies

I have selected a few of the submitted questions and answers to include below. For a full list of questions and answers, please see Ask the Expert – Clinical Stem Cell Manufacturing.

What do you think is the importance of having serum free and/or animal free media in clinical stem cell manufacturing?

The Answer:

Animal-free, chemically defined media would be the ideal choice for all stem cell manufacturing from the standpoint of consistency and control of materials. However, not all cells can be expanded and/or differentiated without serum or other animal derived materials. The use of animal derived materials is acceptable with the appropriate sourcing of materials and testing but most groups developing cell based therapies are working to minimize or remove serum and other animal proteins from their manufacturing process where possible.

Can you explain the difference between autologous and allogeneic stem cell therapies in terms of how they are manufactured clinically.

The Answer:

All stem cell therapies should be manufactured under Good Manufacturing Practices (GMPs). The primary difference between allogeneic and autologous are the source of the cells for the therapy. Allogeneic therapies are manufactured in large batches from unrelated donor tissues (such as bone marrow) whereas autologous therapies are manufactured as a single lot from the patient being treated. For some autologous therapies, the cells from the patient are processed on site at the clinic or hospital. These therapies are not regulated as a biologic product and not produced under GMP but rather the devices used are regulated.

While both therapies use similar technologies common to the growth of cells, the scale is different. Allogeneic therapies are “off the shelf”, used to treat many patients (sometimes thousands) and more time is available to quality control the product prior to administration. Autologous therapies are “custom” products for each patient and the chain of identity of the patient samples is critical to assure the right product is returned to the patient. Scale up of manufacturing for allogeneic cells is similar to techniques used to make protein drugs and other large scale cell derived materials while autologous cells require scale out, the production of many individual products at the same time.

What do you think is the biggest hurdle faced when moving stem cells from lab to clinical manufacturing?

The Answer:

The biggest hurdle in my mind is changing the mindset from research to developing a definition of the product/therapy. There are many technical issues such as scale up, closed system development, serum free media, quality control, etc but none of these can be successfully addressed until you understand the critical aspects of the therapy you are about to test in a clinical trial. It is very easy for a cell therapy to unknowingly drift in characteristics as you go through development into manufacturing. The last thing you want to discover is what once gave you promising preclinical or early clinical results, no longer performs in the same way.

For more information about the topic of clinical stem cell manufacturing, please also see Ronnda’s previous guest blog “From Product Candidate to Product – The Road to Commercialization in Regenerative Medicine.”