The widespread commercialization of stem-cell therapies is still many years away. Only limited information exists in the public
domain for the best method to manufacture products on a commercial scale. The author interviewed industry leaders in stem-cell
regulation, manufacturing, and commercialization to establish: the most likely commercially viable manufacturing process for
allogeneic and autologous therapy; and the annual cost of each stage of the process?
The analysis was based on several key assumptions, which were that regardless of whether autologous or allogeneic therapy:
- Each treatment would consist of the same number of stem-cells (108 mesenchymal stem-cells) and need to be culture expanded for the same length of time (three weeks)
- Each patient would require one dose of therapy
- 2500 doses would need to be manufactured annually to meet the national demand in the United Kingdom for an unspecified medical
- Automated cell culturing would be possible
- Growth factors and media used in stem-cell culture expansion would cost the same. (For further details on methodology and
assumptions, see http://www.biopharminternational.com/biopharm/article/articleDetail.jsp?id=781183 at http://BioPharmInternational.com/.)
The expected manufacturing process for allogeneic and autologous therapy was determined to be similar (see Figure 1). Both
groups would require the construction and running of a manufacturing plant with clean room facilities. Here doses would be
produced via automated cell culturing using media components and growth factors. They would then undergo release testing,
prior to being packaged and transported to a number of key hospitals around the UK that would provide stem-cell therapy services
to patients. The key difference was that for allogeneic therapy, 10 donors would be screened and tested to find one with high
quality stem cells, which would be used to form a cell-bank system that would provide treatments for 10 years. In contrast,
for autologous therapy, each patient would undergo donor screening and testing; their stem cells would be harvested and shipped
from one of the hospitals offering cell-based therapy services to the manufacturing facility for therapy production.
Figure 1: Annual cost of each parameter in a common commercial manufacturing process needed to produce 2500 doses of allogeneic
and autologous therapy per year. (FIGURES ARE COURTESY OF THE AUTHOR)
It was calculated that to manufacture one dose of allogeneic therapy would cost £930–1140 (US$1490–1830; €1030–1260) and to
manufacture one dose of autologous therapy would cost £2260–3040 (US$3630–4890; €2500–3360) (see Figure 1). These figures
include the cost of setting up a manufacturing facility. [For full breakdown of costs, see "Supplementary Material for Allogeneic
Versus Autologous Stem-Cell Therapy: Manufacturing Costs and Commercialization Strategies".] The cost differential could almost
exclusively be attributed to the finding that donor and release testing need to be performed in much smaller numbers during
the large-scale, automated manufacturing of allogeneic therapy when compared to autologous therapy.
DONOR SCREENING AND TESTING
Donor screening and testing are needed to establish a donor's infectious status, genetic predisposition to pertinent diseases
and susceptibility to cancer. Interviews undertaken suggest that donors are likely to be subject to the same degree of testing
whether their stem-cells are used for autologous or allogeneic therapy. It is important to highlight that in-depth guidance
on donor screening and testing has not been published by regulatory authorities.
Equivalent donor screening and testing for autologous and allogeneic therapies may seem counterintuitive given that in the
former stem cells are returned to the patient from who they are harvested, and so less donor testing may be expected. However,
three important reasons exist for equivalent donor testing:
- Cell characterization prior to expansion is needed to verify the identity of the cells.
- Cell abnormalities must be excluded.
- An individual may harbor a latent infection that must not be amplified and reintroduced.
For autologous therapy, each donor must be screened and tested at £990–1320 (US$1590–2110). For allogeneic therapy, 10 donors
will need to be screened and tested to find a high-quality stem-cell sample to establish a cell bank system. It will cost
£9900–13,200 (US$15,900–21,100) to screen and test 10 donors, and £250,000–500,000 (US$400,000–800,000) to create a cell bank
system, which will provide 2500 doses annually for 10 years. Hence, donor screening and testing for allogeneic therapy is
essentially £10–20 (US$16–32) per dose or patient (as each patient is assumed to be administered one dose).
Release testing of the final product is needed to ensure that it is fit for purpose. As with donor testing, release testing
for allogeneic and autologous products is expected to be similar. This may seem counterintuitive because in autologous therapy
stem-cells from a patient are returned to them after culture expansion. In both cases release testing must be performed to
establish product safety, identity, purity, and potency. It could be argued that autologous therapies need more extensive
release testing than allogeneic therapies because of the difficulty in obtaining a uniform outcome due to the inherent variability
in different patients' stem cells.
Release testing is anticipated to cost £300–500 (US$480–800) per batch. In allogeneic therapy, each vial from the cell bank
system will produce a batch consisting of 100 doses. Release testing for allogeneic therapy, hence equates to £3–5 (US$4.8–8)
as only one dose is assumed to be given to a patient. In autologous therapy, each patient's therapy is a batch in itself,
meaning that release testing will be £300–500 (US$480–800) per dose or patient.