Clinical Stem Cell Manufacturing

The role of the pharmacist in the administration of stem cell therapies has yet to evolve, in my opinion. Currently, pharmacists are being utilized in stem cell clinical trials in two ways; 1) to dispense cellular therapies (from a bag to syringes, for example) to maintain the blinding of the physician administering the therapy and 2) to thaw and dilute cryopreserved cells prior to administration. However, the goal of most companies working in this area is to provide the Cell Therapy in a "ready to use" formulation for direct use at the bedside. How successful this will be for all stem cell therapies is yet to be determined.

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.

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.

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.

I think the challenges you describe are definitely still there but do think significant progress has been made in the industry to address them. Cell therapies have been around for more than 20 years despite only a few being approved by the FDA and other regulatory agencies. Many lessons have been learned, especially through the regulatory processes, and there is a lot of collective experience in the industry. Unlike many other industries, there are several groups (ISCT, ARM, etc) that have formed committees to share information and strategies to address the technical as well as regulatory challenges with cell-based therapies