The cancer patient in the regional hospital has immune cells removed from her blood-stream, which are reprogrammed to attack a specific protein in cancer cells, then reintroduced via injection two days later. The modified cells get to work destroying the targeted tumor. This paradigm shift in healthcare and disease treatment, Cell and Gene Therapy (CGT), is expected to revolutionize medicine in the future but the U.S. companies that want to be on the leading edge of this shift are already planning ahead for how and where to focus their resources to exploit this momentous breakthrough in patient care.

Personalized medicine has shifted the role of pharma companies from manufacturer to solution provider, revolutionizing the way healthcare is structured and changing the role of logistics, demanding higher service levels alongside pressure to reduce costs in order for patients to access these life-saving treatments.

Personalized medicine is about bringing the right treatment to the right patient at the right time. It is one of the key vehicles by which the healthcare system of tomorrow can achieve better outcomes for patients while also helping achieve financial efficiency across health systems.

The regenerative and curative treatments inherent in CGT are already seen in the participation of hundreds of companies, with a worldwide market predicted to grow from $18.9 billion in 2016 to over $66 billion by 2022 and a compound annual growth rate (CAGR) of 23.3% in this time frame. The pharmaceutical industry may be moving toward regenerative medicine but there are many significant challenges ahead in taking CGT from a compelling approach to a wide-spread solution backed up by the proven processes, suitable manufacturing facilities and reliable supply chains inherent in creating mainstream medical treatments. These challenges include finding qualified staff, ensuring consistency in manufacturing, having effective logistical systems and regulators that help the development and distribution of advanced therapeutics.

Many U.S.-based biopharma companies already have operations in Europe and this region with its population of 550 million people can provide some advantages over exclusively domestic CGT programs for various reasons. Finding qualified workers at home is more challenging than ever given a U.S. unemployment rate of 3.7%, a 48-year low. The reality of streamlining logistics in this new area of personalized medicine clearly suggests that looking beyond America’s borders for an international manufacturing and strategic support base is an imperative.
Europe already has a long history in the pharmaceutical industry, serving as the location of many strategically important manufacturing sites belonging to U.S. giants like Pfizer, Merck, Janssen and others. In the case of active pharmaceutical ingredient (API) products that gained FDA approval in 2016, 70% were produced in Europe. Besides being well established in the industry, Europe has advantages like its smaller physical size, increasing government research funding and improved IP protection.

However, all European countries are not alike when it comes time to select an optimal location for CGT development and manufacturing. U.S. biopharma companies should be aware of the challenges and have well-thought-out decision criteria before selecting a European host site that will accommodate successful future CGT production. Here are some issues to consider:

Staffing
The supply of qualified workers in Europe varies by country. Scientists, process engineers, validation engineers, quality control professionals, laboratory technicians—these in-demand workers aren’t necessarily plentiful in every possible overseas location. It’s wise to identify countries with a large, well-educated workforce that also includes the support personnel—quality control employees, data analysts and workers in clinical, supply chain, sales, marketing and finance—that will eventually be needed. Given the challenges in working with human cells with their requirements for sterility and consistency, seek a location with personnel that have deep history in manufacturing, particularly biologics, to increase the likelihood of developing the automated processes needed to make CGT cost effective.

One viable approach is to find out where competitors and partners have located because they will have looked at the skilled labor supply before choosing their site. In addition, those competitors already in Europe have probably considered other issues like the cost of real estate, living expenses and other key factors. Ireland is one country that has developed a system for supplying pharma companies with the right talent at the right time. For example, the government-funded National Institute for Bioprocessing Research and Training (NIBRT) in Ireland “trains over 4,000 people each year to develop the talent pool needed to manufacture biologics,” explained Killian O’Driscoll, NIBRT’s director of projects.

Existing infrastructure
Given the challenges in establishing an off-shore CGT operation, reducing risk is paramount. Besides researching European countries with a solid track record in biopharma manufacturing and an ecosystem of suppliers and service companies, search for locations that have a proactive and supportive government system that partners with industry. NIBRT works closely with companies—many of them American—to design what O’Driscoll calls “bespoke training programs” that will address future product lines.

Another benefit of seeking out growth-focused countries is that they’re more likely to partner with U.S. life sciences  companies wishing to establish or expand manufacturing operations. This can extend to help and advice in the planning, construction, permitting and other elements involved in setting up a next-generation manufacturing facility.

Logistics
Logistical issues play a major role when it comes to CGT manufacturing, which calls for having a manufacturing facility with close access to clinics, partners, transportation and other elements. This is required for the “personalized medicine” of autologous therapies, which use a patient’s own cells and require the production of one clinical batch for each individual patient, but distance is also a factor for the allogeneic therapies that use an external donor’s cells.

Europe’s smaller size when compared to the U.S. favors logistical issues, with a good current example being Alofisel, the first allogeneic stem cell product approved in Europe. A remarkable new treatment for Crohn’s disease available from giant Japanese firm Takeda Pharmaceuticals. Alofisel starts with cells extracted from Spanish donors that are then sped to Takeda’s plant in Dublin to grow the cells and complete processing, with the final medicine shipped to specific surgeons to administer to patients.

“The product has a 48-hour shelf life, which is a huge logistical challenge,” said Paul Keogh, Takeda’s plant director at the company’s state-of-the-art Irish facility. “We developed a logistics system that includes minute-by-minute and real-time tracking of the medicines from our plant.”

Takeda is establishing “centers of excellence” throughout the European and Canadian areas—the drug’s initial markets—with the trained medical personnel qualified to administer Alofisel. 

Data
Once we start talking “personalized” all personal data becomes paramount throughout the process.  With the advent of GDPR in Europe it is again important to investigate countries who already have case studies of international companies be they life sciences or other that currently manage and protect data across borders in Europe. A holistic approach will need to be taken to patient data because in this new world the manufacturer is now directly connected and responsible.

Regulators
Clearly, CGT exists in a highly regulated environment. The European equivalent of the FDA, the European Medicines Agency, or EMA, will be involved for the EU and additionally, each country’s own agency will be involved. CGT is a new class of drug product and will have new manufacturing processes that also require approval, thus having a receptive regulatory agency can help companies wishing to successfully get products to market. The best choice is a regulator already working with biologics and advanced therapeutic medicinal products that is preparing for the coming CGT revolution. 

“You need to be based in a location that has expertise, from the regulatory, supply chain, engineering and manufacturing perspectives,” said O’Driscoll. “Ireland really has that biopharma manufacturing cluster.”

Cell therapies have huge potential for the treatment of a range of human diseases including cancer, metabolic disorders, tissue degradation and immune deficiencies. Before these therapies can be effectively commercialized for widespread and cost-effective clinical use, however, there is a need to find robust, repeatable and scalable ways to generate large volumes of cells and test to ensure they are a safe and effective therapy. Setting up a European operation can help U.S. biopharma companies speed up their participation in this far-reaching next step in medical care and get these advanced treatments to a wide patient population.