The Epicenter

A first of its kind collaboration center aims to facilitate the discovery and development of a new generation of nuclear imaging agents.

Approximately 1.7 million clinical PET studies were performed in the country in 2010, with 94% of them using radiopharmaceuticals that were purchased from an outside vendor, according to a recent report released by IMV Medical Information Division. The remaining 6% used agents from on-site cyclotrons.

All in all, the market has seen an average growth rate of 7.1% over the past 2 years, the report continued.

Although the estimated figures suggest a slowing in the annual growth rate for PET patient studies, which boasted an average growth rate of 10.4% between 2005 and 2008, the latest numbers still demonstrate significant growth.

The technology is currently largely applied in the oncology setting, accounting for 95% of all PET studies. Nevertheless, the report states that neurology and cardiology applications, which make up the remaining 5%, are expected to comprise a larger proportion of future studies as other radiopharmaceutical tracers become approved for clinical use.

Addressing this shifting demand in the marketplace, one health care services provider has established a “first of its kind collaboration center,” a laboratory that aims to expedite the development of nuclear imaging agents that treat diseases such as cancer, heart disease, and neurological disorders. Responding to the rise in its volume of business, Dublin, Ohio-based Cardinal Health recently opened The Center for the Advancement of Molecular Imaging in Phoenix, Ariz.

“The mission for the Center is to accelerate the production of new and novel agents into the marketplace,” said John Rademacher, president of Cardinal Health’s Nuclear and Pharmacy Services. “That is at the core, and this investment really has been to help the future of molecular imaging by supporting our innovation partners in the way that they develop and distribute the novel new agents through the clinical trial up until the commercialization process. Our contribution is really to put our experts together to help solve some of the most difficult issues facing the imaging modality, from the chemistry to the technology that supports it, as well as the quality and regulatory affairs and the way that we manufacture the product.”

From Idea to Implementation

Historically, Cardinal Health had concentrated on building out its network rather than bringing it inward. Specifically, its scientists would travel to each of the facilities that requested assistance with clinical trial doses. At each individual location, they would manage the process in that particular environment, essentially supporting the clinical trial process on a site by site basis.

“In discussions with our innovation partners and academic research partners, we realized that the ability for us to centralize a lot of that functionality, to really have a one-stop shop where all of the needs of that initial setup of being able to manufacture and then roll out to multiple sites [could be met], was of high value to those partners and also proved to be a much improved business model from our perspective,” Rademacher said.

After identifying centers of excellence and, more importantly, the desired footprint, Cardinal Health decided that the Phoenix area was the ideal location. The 25,000-square-foot campus aims to assist pharmaceutical companies and academic research institutions in accelerating the development, testing, commercialization, manufacturing, and dispensing of new radiopharmaceuticals and PET imaging agents. Partners include Ohio State University, University of Washington, Michigan State University, Moffitt Cancer Center of the University of South Florida, Eli Lilly, GE Healthcare, and Lantheus. According to Cardinal Health, the Center will usher in more than 35 new, high-technology jobs, including roles for radiochemists, engineers, scientists, product development managers, project managers, and quality and regulatory personnel.

Rademacher explained that the campus houses four separate operations with distinct capabilities. For example, collaborative laboratories aspire to connect industry innovators with experts in the fields of scientific research, technology, quality and regulatory affairs, and manufacturing. The goal is to discover new ways to decrease the time it takes to secure FDA approval of new imaging agents, as well as share best practices for commercialization.

In the PET manufacturing facility, the Center will manage the commercial production of products that are available and for sale today in the marketplace. Among the advanced technologies are dual cyclotrons, used in the production of large quantities of radioisotopes. Furthermore, production facilities will allow for the simultaneous radiosynthesis of multiple imaging agents for both commercial and research purposes, according to Cardinal Health.

In dedicated, fully functional private laboratories, guest researchers can conduct experiments that will produce, test, and develop radioactive products. As of press time, the Center is in negotiations with six parties that are looking to utilize these spaces. Cardinal Health’s goal is to help bring about more rapid deployment into large-scale, multisite clinical trials.

“We have an open environment that allows for collaboration and interaction, training facilities that can be utilized, spaces for them to have their own separate workstations and huddle rooms to continue to advance and work on their own, plus areas in which our teams can interact and can brainstorm and innovate,” Rademacher said.

Lastly, a global PET Production Control Center will permit pharmaceutical companies and academic institutions to gain access to video monitoring of each of Cardinal Health’s PET manufacturing sites during clinical trials. Described as a type of “mission control,” the Center facilitates trouble-shooting, offers technical assistance, and deploys resources against manufacturing challenges.

“The development and launch of the Center itself has been a true partnership across many functional areas of expertise within Cardinal Health,” said Benson Yang, vice president of sales for Cardinal Health’s Nuclear and Pharmacy Services and project lead for the Center. “Our scientists, chemists, and regulatory affairs and production experts helped us to develop a truly state-of-the-art facility that helps expedite all stages of the development and commercialization process. Information technology, corporate real estate, and marketing communications experts also helped us ensure the facility was optimally designed to facilitate collaboration and the open expression of new ideas. We are very pleased at how quickly the team embraced and implemented this common vision.”

Leveraging Expertise

As a first of this type of venture, one key challenge for the Center is to think ahead about the needs of customers. Rademacher said Cardinal Health ensured that the voice of the customers was included in the facility’s ultimate design. Yang concurred. “We spend a lot of time talking with our partners in the radiopharmaceutical supply chain to identify additional ways we can move the molecular imaging industry forward. When it came to developing the vision for the Center, we started there, capturing informal customer input we’ve gathered over the last few months and years. We wanted to make sure the Center was designed to effectively address many of the collaboration needs and pain points our customers have expressed over the years,” said Yang.

Well-choreographed and coordinated collaboration is extremely critical, Rademacher continued. The Center seeks to follow the Lean Six Sigma process improvement methodology, which looks at the entire flow of process from inception to delivery and strives to take waste and errors out of the system. Providing the example of F-18 fluorothymidine (FLT), a PET agent with a 109-minute half-life, Rademacher emphasized that not only is proximity to manufacturing very important but also tight logistics around getting the product into the marketplace in support of clinical trials. “Because you are dealing with such short shelf life on these products, the ability to have a team together that is thinking about ways for process improvement and focused solely on the element associated with the unique manufacturing needs of this type of product is critical,” he said. “Our ability to centralize a team who focuses on improving that process from manufacturing, engineering and equipment, and quality assurance areas is a substantial benefit for us and our innovation partners.”

Satoshi Minoshima, MD, PhD, professor and vice chair of research for the Department of Radiology and Bioengineering at the University of Washington, said that by academia pairing with industry, new concepts and new tracers are brought to the initial phase of testing. For instance, F-18 FLT—which was discovered by one of Minoshima’s team, John Grierson, PhD, in his laboratory—has the ability to detect cancer cell proliferation. Today, Cardinal Health manufactures this radiopharmaceutical. “By working with Cardinal, we can make a translation of initial investigation into clinical trial and eventually get a clinical application much faster,” Minoshima said.

Eye on the Future

Yang believes that the types of entities that will be most interested in engaging with the Center are pharmaceutical companies and academic research institutions that are looking to commercialize novel new PET biomarkers. “We believe that the Center will sufficiently reduce the administrative costs associated with radiopharmaceutical drug development, and it will provide a point of entry to the US health care market for global companies that are developing new biomarkers,” he said. “This streamlined process will help reduce the barriers to entry for those looking to bring new novel agents to the marketplace. One of the Center’s goals is certainly to benefit nuclear medicine departments of hospitals of all sizes, by expediting the development of new imaging agents that can help detect and track chronic diseases, and by making those imaging agents more accessible.”

In terms of immediate goals, the Center is currently working with its innovation partners to improve and perfect the way that their manufacturing process operates. “That’s something that is at the forefront of what we do,” Rademacher said. “We’re also taking a look from an end-to-end standpoint at the entire manufacturing process and ways of improving. That includes everything from the way that the cyclotrons are operating and how they are turned, through the synthesis process.”

Also, Cardinal Health has 13 provisional patents on new innovative technology and equipment in the works. Rademacher explained that the Center is looking at its drug delivery system, in particular how to transport products from the pharmacy to the patient in the most safe, economical, and efficient way. “We are really looking from the creation of the isotope that starts with the cyclotron to the actual injection of the patient and trying to find ways to innovate and improve across that entire spectrum of opportunity,” he said.

In Minoshima’s eyes, Cardinal Health’s role is crystal clear: to facilitate the development of a new generation of molecular imaging tracers. “They are not claiming that they have a ton of ideas to develop tracers,” he said, “but everyone acknowledges that from idea to clinical application, it’s really a challenging path that requires time, expertise, infrastructure, and resources. Establishing this lab to help investigators and industry partners is a great idea.”

“We really look at our role as an enabler, not doing the benchmark discovery ourselves,” Rademacher agreed. “Our organization really looks at our role as being a small ‘r’ in the research and a big ‘d’ in the development. We really leverage our experience in handling radioactive materials, in the manufacturing, dispensing, and distribution of those, and we allow our research partners to focus on what they do best, which is the research and discovery of new medicines and new imaging agents. That’s what the Center is about: to allow our partners to focus on what they do great, which is research and discovery, and allow us to leverage our expertise in support of that.”

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Elaine Sanchez Wilson is a contributing writer for Axis Imaging News.