Stem cells have been used successfully for over 50 years in the treatment of patients in the context of bone-marrow transplant [1]. However, over the last 15 years the use of stem cells as potential therapies has been subject to both high levels of hype and a lack of significant commercial success, since the first embryonic stem cells were discovered in the late 1990s [2]. While regenerative medicine is a billion-dollar industry today, it is still quite small given a single drug can generate many billions of dollars in revenue [3]. This apparent lack of commercial success could be attributed to a variety of factors, including lack of significant funding, limited success of clinical trials, uncertainty around business models [4], and an overall misunderstanding of stem-cell biology by the public. However, there are some key learnings that can be culled from the regenerative medicine industry over the last 15 years. This chapter will focus on addressing some questions surrounding these, including:

1. How does the process of commercializing stem-cell products differ from that of biopharmaceutical products or medical devices?
   
2. Over the last 15 years, what cell-based therapies have been commercialized?
   
3. What are the key learnings (both good and bad) that can be gained from analyzing these therapies?
   
4. What are the special challenges to commercialization of stem-cell therapies?
   
5. What are the key learnings for a scientist to keep in mind as they move an asset through from concept to the clinic to commercialization?
   
6. What is the right strategy for translating a new therapy into the clinic and beyond?
   
7. What are the key activities to consider for successful translation of a concept into a company?

A key question is: How does commercialization of cell-based products differ from commercialization of other traditional medical therapies? We can evaluate three major categories of medical therapies: small molecules, biologics (large molecules), and medical devices. Small molecules have been commercialized for years using traditional approaches in marketing, such as hiring large numbers of sales reps to detail physicians (both primary care and specialists) in order to provide widespread information about the product [5]. The key to success is strong marketing, competitive differentiation from other products, and low cost of goods (COG), which can drive both revenue and profitability [6]. While biologics have traditionally been focused on specialist markets, given their overall higher pricing, the detailing and push to reduce COG are critical for profitability and the overall model is not significantly different from that of small molecules. The primary difference is that most biologic products must usually be kept cold (storage temperatures vary), which presents important logistical considerations versus small molecules. Reimbursement for both types of product is similar, although biologics are often more expensive than small molecules. In addition, both biologic- and small molecule-based products can cost many hundreds of millions of dollars and can take 10 or more years from early discovery to market launch [7]. However, once an asset is on the market, it enjoys exclusivity for a period of time, until patent expiry (which in some cases can be 10 or more years post-launch). While loss of market exclusivity typically results in a small-molecule product losing 80% or more of revenue within a year or two, biologics have yet to be significantly impacted by loss of exclusivity. In fact, although several biologics have experienced patent expiry there are few launched generics or biosimilars on the market, with those that have launched experiencing minimal commercial revenue [8].

Medical devices are typically complex pieces of metal and/or plastic sold primarily to surgeons or other specialists. Companies selling these devices utilize a different commercialization model from that for small and large molecules. Medical devices typically have higher COG than small molecules or biologics [9]. There are several reasons for this, including the higher production costs, relatively lower selling price, and need for more complex sales-force detailing. A typical medical-device sales rep will often be present and assist in the training of physicians in the use of the device, which builds a strong relationship with the physician but also results in higher costs for the selling company [10]. In addition, while the product lifecycle for biopharmaceuticals is long, that for a medical device is quite short, given the perpetual innovation that occurs in this space. This means companies must rapidly develop new products without the long R&D cycles common with biopharmaceuticals. Given the very different business models and COG, there are few companies that sell products which use both the device and the traditional drug model. Johnson & Johnson (J&J) is the one large-company exception, as it has been successful selling both medical devices and traditional small-molecule and biologic products [11]. Most other companies in the space are focused on either traditional biopharmaceuticals or medical devices.

The models described here are well-established in the market, such that physicians, sales reps, manufacturers, payers, and even patients are comfortable with them, despite their differences. How does cell-based therapy fit into this? Such therapies can possess elements from both the biopharmaceutical model and the medical-device model [12]. For example, a cell-based therapy will likely require some type of cold-chain distribution, not unlike biologics. However, it may require more complex provisioning and hence a field force that is more akin to that for a medical device. This mix of models makes cell-based therapies problematic for both traditional medical-device manufacturers who are not familiar with cold-chain logistics and distribution and biopharmaceutical companies that are not familiar with the complex sales and marketing requirements of devices, not to mention the relatively lower gross margins. In addition, the business model will differ between an autologous and an allogeneic therapy [13]. We will not delve into the business-model and scientific differences between allogeneic and autologous therapies, as this has been covered elsewhere [4, 9, 12,13]. However, J&J demonstrates that it is possible for a company to be expert in both business models, and it is therefore likely that once commercial cell-based products are on the market, medical-device and biopharmaceutical companies will adapt to be successful in selling them.