Incomes currently generated by the global cell therapy market are estimated to be ~US$400 million. That value represents 10 main products, some of which have been on the market since the late 1990s (e.g., Dermagraft and Apligraf, with >$100 million yearly revenues each). Cell therapy product revenues are low compared with those of the biopharmaceutical market (~$100 billion). But the market’s growth potential and clinical pipeline are leading to higher expectations. The sector’s compound annual growth rate (CAGR), for example, is predicted to reach at least 20% (
1
).
Recent filings support those market growth expectations. Two products received FDA approval in 2011, LaViv dermal filler based on autologous fibroblasts (Fibrocell) and Hemacord cord blood hematopoeitic progenitor cells for blood disorders (NY Blood Center). Moreover, Provenge therapeutic cancer vaccine for prostate cancer (Dendreon) and Chondrocelect product for cartilage regeneration (Tigenix) continue to gain momentum in their respective ...
+2The introduction of recombinant proteins and monoclonal antibody (MAb) products revolutionized the treatment of many diseases, including diabetes, rheumatoid arthritis, multiple sclerosis, Crohn’s disease, cardiac disease, and cancer. These highly specific biologic therapies provide patients with life- saving approaches that are not possible with small molecules. MAbs in particular are a unique class of biopharmaceutical products that interact with and activate components of the immune system to provide such therapeutic benefits as tumor destruction by antibody-dependent cell-mediated cytotoxicity (ADCC). Other biopharmaceutical products such as growth factors can activate receptors and stimulate a cell-based response, and enzymes can provide critical function in target tissues. In addition the unique affinity and specificity of biologic molecules to bind tightly to receptors and cell surface antigens can be exploited to deliver highly potent payloads to target tissues. The recently approved Adcetris drug...
+1 After coexisting as close cousins in the world of life sciences, the bioprocessing and cell therapy industries now find themselves as possible allies in the pursuit of solutions to small–batch-size production technology. As cell culture titers continue to increase and biotherapies become more “personalized,” pressure is increasing on the bioprocessing industry to find more cost-effective and flexible technologies for producing smaller batch sizes than before. At the same time, the cell therapy industry (renowned for its small–batch-size production) continues to gain momentum, with a significant number of therapies now in clinical trials. Cell therapy companies with products in clinical trials must address the critical challenge of establishing their own approved processes suitable for commercial-scale good manufacturing practice (GMP) production.
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Closed, integrated processing technologies address many converging needs in both the bioprocessing and cell processing markets, enabli...
Adherent cells such as adult primary cell lines and human multipotent (MSCs) and pluripotent stem cells (hPSCs) present a manufacturing challenge as lot sizes increase from 10
9
(billions) to 10
12
(trillions) cells (
1
). Typically, manufacturing platforms are good for one log of expansion. So new methods will be required to achieve commercially relevant lot sizes. Traditional two-dimensional culture methods have been used to grow anchorage-dependent cell types. Although such methods are reliable and well defined, they are very labor intensive and limited in scale-up production potential by the available growth surface area (Table 1). Allogeneic “off-the-shelf” therapies based on adherent-cell platforms may require manufactured lot sizes from 100 billion to a trillion cells depending on a given indication’s market size (
2
).
Table 1. Projected lot sizes by production platform in number or unit operations, total surface area per harvest, and total cell numbers, with robotic manipulation of four large v...
+3 Many companies follow a general rule when assembling regulatory packages for presenting new biologics: Accentuate the aspects of your new biologic that mimic approved therapies. For companies working on cell-based therapies, however, that is a challenging task. The industry lacks established models, and the current European Medicines Agency (EMA) regulatory definition of a cell-based therapy is simply “an advanced therapy medicinal product” (ATMP) (see EMA guidance box).
Regulations for cell therapies cannot always be compared directly with those for other biologics ()
One potential strategy is to deconstruct aspects of the therapeutic product profile (TPP). This can help you determine which components of the clinical function, upstream, and downstream processes approximate existing products and apply similar principles. As with other products, emphasis should be placed on a risk-based approach.
Defining Final Products
Many aspects of regulatory requirements governing approval of a novel biologic are link...
Geron Ends Stem Cell Programs in November
: Big hope for a spinal cord injury trial, big loss for a field — the most discussed news of the year. Despite the company’s official comment citing a “purely business decision,” many professionals think that a “lack of impressive preliminary results” also played a role. The company is now seeking a partner to take over that trial. The effect on the cell therapy industry remains to be seen — but for some developers, scientists, and patients it’s a big loss. We will remember Geron as a pioneer in clinical translation of embryonic stem cell therapy, a prototype developer and trailblazer in the regulatory path.
First Patients Treated with Embryonic Stem Cell Products
: Despite Geron’s discontinuation, five spinal cord injury patients were treated. And as far as we know, none of them developed complications or adverse events related to their treatment. But we don’t have any information about functional improvement in disease course. Another company — Advanced Cell Tec...
The cell therapy industry (CTI) is no longer a cottage industry; it is a distinct and sustainable component of the global healthcare sector (
1
). Today, CTI prospects are strong, with annual revenues exceeding US$1 billion/year, supported by improving investor sentiment and public support (
1
,–
3
). The next phase of CTI growth — toward a multibillion-dollar global industry — will depend on the biomanufacturing community innovating to meet growing market demands and providing products at affordable costs to healthcare payers.
Currently, the majority of cell therapy clinical trials are in phases 1 or 2 (
4
). However, as more CTI companies break the phase 3 frontier, clinical trials and regulatory requirements are becoming increasingly more predictable. This enables new companies to start out with a focus firmly on commercialization, using lessons learned from preceding trials to streamline their manufacturing processes and minimize the time to market.
Here we propose a simple requirements-based framewor...
+2 Potency testing is defined in 21 CFR Part 600.3(s) as “the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result” (
1
). Potency measurement is especially important for complex products such as cellular therapies (CTs). It is considered an essential aspect of the quality-control system for a CT drug substance and drug product. It is performed to assure identity, purity, potency (also called
strength
in FDA documents), and stability of products used during all phases of clinical study as well as for licensed products (
2
,
3
).
As such, potency assays are used, along with other analyses, to demonstrate that only product lots that meet and continue to meet defined specifications or acceptance criteria are administered during all phases of clinical investigation and following market approval (
2
). In addition, potency is measured ...
Development and manufacturing of a therapeutic stem cell product requires extensive quality control (QC) to ensure the identity, quality, and safety of the cells. Here, we describe our QC pipeline to optimize the manufacturing of our MultiStem adherent stem cell product, which is in clinical trial testing for stroke, acute myocardial infarction, inflammatory bowel disease, graft versus host disease, and solid organ transplantation. Screening for growth, marker expression, immunosuppression, and multipotent differentiation — in combination with “-omics” screening for gene expression, DNA methylation, and miRNA patterns — provides a comprehensive characterization of the cells, which facilitates further optimization of the manufacturing process.
The product
The application of adult stem cells in regenerative medicine has gained strong interest during the past decade. Clinical trials are investigating the efficacy of stem cells to treat disorders such as neurodegenerative and cardiovascular disease, immune d...
+1 
