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Cell therapy, such as immune cell and stem cell-based therapies, offer attractive alternative approaches to more widely used treatment options. However, before these can become suitable as effective therapies, there are several manufacturing, formulation, and handling challenges that need to be overcome. Of these, product heterogeneity is one of the main concerns and can arise during the entire value chain, from harvesting, upstream culture, and cell preservation, to cell therapy administration. Consequently, pharmaceutical companies are striving to understand and control all steps to increase cell viability and minimize variability.
Current treatments
Cell therapies are being developed for numerous applications and diseases such as type 1 diabetes, where patients are given cells that express insulin or that act together to simulate the function of pancreatic islets. Additionally, two recent approvals, Kymriah (Novartis) and Yescarta (Kite/Gilead), use the patient’s own T cells that are harvested and modified with viral vectors to express chimeric antigen receptors to the CD19 receptor on cancerous cells in acute lymphoblastic leukemia and large B-cell lymphoma respectively.
The advance of stem cell therapies presents several challenges, including the sourcing, manufacture, formulation, cryopreservation, and logistics associated with cell therapies. All cell therapies require that good manufacturing practices are followed and considerations must be given to ensuring purity, potency, and identity.
Cell therapy evolved from more traditional cell culture methods which often involved the use of animal- or human-derived materials such as animal or human serum albumin in the manufacture, preservation, or formulation of these products. Animal serum and human serum albumin (HSA) have been found to be useful stabilizers in cell culture media and preservation media. However, due to regulatory concerns over blood-borne contaminants (mycoplasma, viruses, and prions), potential issues with reliability of supply and the performance variability of HSA and undefined serum between suppliers and between batches, there is an increased demand for a more defined and consistent animal origin-free recombinant alternative.
An alternative approach
Albumin is long-established as an ingredient of cell-culture media for its ability to facilitate growth of many cell types. The industry is now seeing its properties expand for use in the cryopreservation and formulation of stem cell therapies. Regulatory pressure and the need to improve safety mean that recombinantly produced excipients, growth factors, modifying biologic agents, and cryo-protectants are becoming the norm. Recombinant human albumin provides a superior safety profile and demonstrated drug stabilization performance, providing an ideal, low-risk stabilizer for cell culture and formulation. The use of fully recombinant human albumin, especially in the cryopreservation of stem cells, is demonstrating new potential for the regenerative medicine field.
Cryopreservation
Albumin is often used as a component of cryopreservation media, along with agents like DMSO, simple salts, and buffering agents to maintain pH and isotonic conditions. Albumin enables cells to endure the transition from growth media and the harsh state change during freezing. Albumin’s benefits derive primarily from its ability to coat surfaces, its buffering capacity, and its ability to bind and transport nutrients and toxins and stabilize the cells. The use of recombinant human albumin in cryopreservation provides a longer viability window for logistics, transport, and administration.
Formulation
The development and use of a controlled, consistent, and reproducible media can ensure purity, potency, and identity of therapeutic cells and aid in a smoother regulatory review and release. Controlled media can also reduce the background of any biological assay. Such features allow agencies to focus on the therapy itself and not be as worried about potential effects of media variation or impurities. However, it is not sufficient to focus on utilizing controlled media only at the final formulation step due to carry over from sourcing, expansion, and transformation. In the case of recombinant human albumin, it has been shown to enhance expansion and improve fidelity of transformation prior to cryopreservation and final formulation. Designing in controlled media using substances like recombinant human albumin earlier in the process can help to ensure process consistency, quality, and reproducibility while potentially reducing scrutiny of the media by regulatory bodies.
Conclusion
Stem cell therapy is a cutting-edge therapeutic field, but still young and with a lot of room for optimization to ensure they reach patients. Recombinant human albumin offers a safe solution for optimized cell performance. As an animal and human component-free product it provides regulatory benefits while improving cell viability and controlling batch-to-batch consistency. Solving the processing and formulation challenges in the field of cell therapies is a daunting task; using an ultra-pure recombinant human albumin source in the downstream processing of cell therapies offers advantages along the entire value chain.
Phil Morton, PhD, is the CTO of Albumedix.
