There is much scientific evidence of the early successes of whole cell therapies as disease cures in chronic conditions and disease-modifiers in acute conditions1 but limited cases of successfully transferring these discoveries to commercial products or therapies. Many factors contribute to this, including a lack of scientific understanding of whole cells as therapies, the late consideration of process engineering, a lack of defined business models and a reactive rather than a proactive management style.
As with pharmaceuticals and biopharmaceuticals, without intervention, the successful transfer of effective whole cell therapy treatments to the market will follow a linear model, which generally means it takes approximately 20 years from the point of discovery for a product to reach the market. This linear route — from discovery to process design and development through to commercialisation and market launch — is often lengthened by iterative transfers back to previous stages because of inefficient knowledge capture and transfer. Although this business model is ingrained in pharmaceutical and biopharmaceutical industries, it does not have to be the case for cellular therapies.
Finding a quicker route to marketWe have studied and evaluated the timeline delays encountered in the development and commercialisation of mature therapeutic protein products. Based on this information, it is possible to make informed decisions concerning the development of whole cell therapies. For example, novel reactors such as airlift and membrane bioreactors2,3 developed for the production of therapeutic proteins are now largely redundant because of their complexity and non-robust performance. Therefore, the development of similar reactors for whole cell therapies should be avoided and focus should be on the use of existing technologies for cell culture.
Whole cell therapies can be broadly grouped into two categories: autologous where the patient is the donor, and allogeneic where one donor (after appropriate cell expansion) can treat all patients. Both face distinctly different bioprocessing challenges; for autologous treatments, the logistics of bespoke medicine are most prevalent, whereas for allogeneic treatments the biggest challenge is production scale.
The first cellular therapies to be successfully launched will probably be autologous treatments that do not require immunosuppression. Because these therapies have a market size of one, it is best to treat them as clinical applications rather than pharmaceutical products so that they reach the patient with speed. There are a range of different operational business models that may be considered for biopsy, culture and implantation of autologous cellular treatments — these range from the ideal (all processes completed on one site) to those that are more economically viable, such as a hub and spoke model.
Preclinical trials involving the transplantation of limbal stem cells to treat unilateral limbal stem cell deficiency caused by chemical eye burns are currently being conducted at Newcastle University (UK). Using this cellular therapy as a model, we can explore how such a treatment may be scaled up and adopted by a country's health service. It is also possible to explore which model of operation is most appropriate to benefit patients, healthcare practitioners, investors and to fit within the current healthcare infrastructure.
Allogeneic whole cell therapies are more closely aligned to the philosophy of biopharmaceutical manufacture and are, therefore, likely to face similar scale up challenges when it comes to meeting market demand. Our evaluation of limbal stem cell transplantation business models will also consider the effects of a future transfer to an allogeneic model.
The limbal stem cell study is an example of using proactive business modelling to shorten the timetomarket for a cellular therapy. By examining the economics and practicalities of the logistical routes to deliver the treatment to patients at this stage will inform future development and prevent bottlenecks occurring when this stage in commercialisation is reached. Assessment of all routes and development of the most viable one (for example finding the right GMP facility and defining shipping conditions) could shorten the transition to commercialisation by an estimated 2 years. If people throughout the entire development process collaborate more closely, it will help to streamline development and enhance knowledge transfer. Ultimately, this will help reduce the time required to bring an effective treatment to market. Benefits will accrue in the form of reduced costs and longer patent protection when a product becomes commercially available.
1. C. Mason and P. Dunhill, Regen. Med., 4(6) 835–852 (2009).
2. A. Margaritis and J.B. Wallace, Nature BioTech,. 2 447–453 (1984).
3. M.W. Glacken, R.J. Fleischaker and A.J. Sinskey, Trends Biotech., 1(4) 102–108 (1983).