Improving Stability of Cells – An Alternative to Complex Logistics for Cell Therapies31 Mar 2020
The cell and gene therapy industry has, over the past years, proven its potential and many patients are now benefitting from advanced therapies with dramatic clinical results. Increasing clinical activity in diverse and more prevalent indications is prompting considerable effort and progress in addressing various manufacturing and logistical challenges in order to make more practical and scalable therapies. This blog will explore some specific examples and look at how the industry can address them by improving stability, quality and consistency of materials and reducing some of the existing bottlenecks which may impact therapeutic success.
Cell therapeutics have the potential to transform the treatment of a wide range of diseases, such as cancer, neurodegenerative disorders and autoimmune disorders. According to the Alliance for Regenerative Medicine1, there are more than 900 regenerative medicine companies worldwide, with 2019 being a significant year of growth for the regenerative medicine sector. Recent approvals in the United States and the European Union for GSK, Tigenix, Novartis and Kite (a Gilead company) are helping to better define success criteria that move more cell therapies to the marketplace meaning there is growth in every area, including therapies, size of indications and patient numbers being targeted, clinical sites and shipping volume.
Cell therapies contain living cells, which makes them a valuable treatment. However, it is exactly this living nature of cell therapies that poses the most challenges. The process of getting such treatments to patients is complex. Over an extended period of time, most cell therapies will not remain viable at ambient or even refrigerated temperatures. This has implications for distribution strategies and logistics. For instance, for an autologous therapy where a product involves moving patient cells to a processing facility and then sending the processed therapeutic cells back to the patient’s physician for treatment, the timeline is quite complicated. Add to this geographical growth, with the evolution from “one-off” clinical trials to large scale studies and commercial role out, the challenges intensify.
A lot of time and effort is being put into how logistical challenges can be solved, getting product from the manufacturing sites to the clinical sites “just in time” for administration. Essentially you are trying to “keep people from being people” in a hectic hospital setting, with patients not always arriving on time and personnel being busy, whilst dealing with therapies that have very short viability windows. Some clinics are also not optimally prepared to handle cryopreserved treatments. With MIT NEWDIGS1 estimating that 500,000+ patients will be treated with cell and gene therapies by 2030 in the US alone, solutions need to be investigated now to overcome future logistical challenges. Transport temperature and managing freeze and thaw in the clinic poses considerable issues.
The extent to which a cell therapy can be frozen and thawed and maintain its activity impacts distribution decisions, as does the length of the product’s stability at various temperatures. Although both pose challenges, a product with a shelf life of only a few hours poses substantially greater logistical issues than a product that remains stable post thaw for a few days or even a week. Addressing distribution and logistical challenges is an important issue on several levels. In an early stage clinical trial, when manufacturing occurs on-site and distribution is not required, certain cell therapies will prove very effective. However, when applied to a clinical setting, when distribution is required, the product may be less effective in a “real-world” situation due to reduced cell viability. The shipping window is often driven by the patient, and onsite storage and space constraints can play a part.
All the efforts to solve these issues are focusing on setting up logistical circumstances that allow for ‘just in time administration’ - in the narrow window where the therapies are viable for administration. But what if we’re thinking about this the wrong way?
Our argument is that instead of only talking about how to squeeze through this narrow crack in a therapeutic window, to instead “just” expand it by increasing the stability of the cells, making them easier to handle and more robust to any changes in a treatment schedule.
Recombinant human albumin can be utilized for stem cell culture, cryopreservation and formulation. Ways that Albumedix´ recombinant human albumin can provide stability to the cells is in the cryopreservation and thawing of the cells. By adding albumin in the freeze/thaw process, cells are kept more viable post-thaw for a longer time. Cryopreservation data suggests that stability can be increased three-fold (from 24 hours to 72 hours) changing the conversation around what is achievable in cell therapy.
The role and function of Albumin in cell therapy
Albumin is a long-established ingredient of cell culture media, well known to facilitate growth of many cell types, such as mesenchymal stem cells (MSC’s), embryonic stem cells (ESC’s), induced pluripotent stem cells (iPSC’s) and immune cells. The exact role of albumin in cell culture is not fully established, however after decades of use, its relevance and benefits in cell therapy applications cannot be disputed. Today, several of albumin’s biological properties have been proven valuable across the cell therapy value chain, including:
- Transportation and complexation with metals or other beneficial molecular entities, creating an optimal micro-environment for sustained cell viability.
- Acting as a rich nutrient source ensuring optimal conditions, particularly during cell proliferation.
- Functioning as a pH buffer to prevent unwanted effects during differentiation.
- Maintaining cell viability during cryopreservation - driven by the high purity of our recombinant albumin.
- Acting as a scavenger of toxins and other reactive oxygen species, albumin protects cells against chemical stress all the way from culture to patient.
- Providing an insulation effect in media due to its propensity to distribute evenly throughout solutions.
The actual function of albumin in cell culture, cryopreservation and stem cell formulation is believed to be a combination of these properties. Our recombinant human albumin products (Recombumin) has been specifically developed to enhance these functional properties – giving developers more confidence in their cell therapies. Data additionally shows that with the addition of Albumedix recombinant human albumin, cells are kept from entering late apoptotic state, thus ensuring the cells which are being administered are more efficient as well. Listen to our webinar for more information on this.
As clinical and commercial therapies make headlines worldwide, such as Zynteglo, Zolgensma, LUXTURNA, Yescarta and Kymriah, the cell and gene therapy industry is buoyed with enthusiasm and potential. Many patients are already benefitting from regenerative medicines, and the clinical results are dramatic. New therapies are entering clinical trials like never before, covering ophthalmic conditions, cardiovascular disease, musculoskeletal disorders, autoimmune diseases and endocrine, metabolic and genetic disorders. With this growth, underlying challenges, such as scale-up manufacturing, the need to reduce costs, the increasing demand for quality starting materials and the logistical issues in getting those products, typically shipped fresh from the clinic or processing center to the manufacturing facility, need addressing now.
There are many time-sensitive elements within the cell and gene therapy supply chain and these present critical challenges. Albumedix can help address these challenges. Increasing stability means therapies can be handled more like traditional therapies - shipped, stored, brought out as needed – in and ideal world, like protein therapies. As certain indications become more prevalent, like diabetes for example, the continual striving to develop cell therapies that deliver optimum stability will make a big impact: for patients (who will have more flexibility about how treatment is managed), for hospitals who could consider centralized cryo-units to store therapies allowing many more hospitals to offer treatment, not just specialist centers as we see now for select rare disease etc. In addition, therapies that are wasted because they fail in a limited window will be minimized, resulting in cost and patient benefits.
We are making considerable effort and progress in addressing various manufacturing and logistical issues, for the success of drug developers, clinicians and patients. We can all collaborate to develop new and different therapies, empowering excellence across the industry to push new therapies as far as possible – to the benefit of all. There is a need for global systems that can provide quality, consistency and collaboration. If you would like to start a conversation with us on scalable and practical therapies please contact via this form.
- Regenerative Medicine Sector Overview, Alliance for Regenerative Medicine, Janet Lambert, CEO, ARM https://46ax7g7nqmq3divu13d9zsn1-wpengine.netdna-ssl.com/wp-content/uploads/2020/01/Janet-Lambert_ARM_Phacilitate-2020_FINAL2-1.pdf