Innovations: The Future of Pharmaceutical Facilities
Opening keynote addresses at the 2023 ISPE Facilities of the Future Conference focused on innovation in planning for future pandemics and reinventing medicines for a healthier world. The two-day conference on 31 January–1 February featured a range of sessions on topics including biomanufacturing, cell and gene therapy, digital transformation and Pharma 4.0™, emerging technologies, and facility design and construction.
The conference opened on 31 January with a welcome message from Thomas Hartman, ISPE President and CEO, who said that there were more than 400 attendees in the North Bethesda, Maryland, conference site and in virtual attendance. Hartman noted the importance of attendees’ work in bringing pharmaceuticals to patients. “You play a very, very important role in the patient equation,” Hartman said.
Addressing Future Pandemics
Matthew Hepburn, MD, Senior Advisor to the Office of Science and Technology Policy Director on Pandemic Prevention, US OSTP, Executive Office of the President, presented on “Innovation in Manufacturing to Address Future Pandemics” in the first keynote of the morning on 31 January. A previous presenter on issues related to the pandemic, he observed that it was good to be able to return to reflect on “where we were a year ago and where we are today.”
The shift from addressing the current COVID-19 pandemic to innovation and preparation for the next pandemic and the broader considerations of “what we are trying to do with human health” have consumed Hepburn’s work and he shared some of the findings and foresight about what lies ahead. One lesson learned, he noted, is that there are many international partnerships now with the US since infectious disease response is a global issue. As a fundamental principle of infectious disease, if you can stop or contain outbreak very early on, and stop exponential growth phase, you can achieve a much better outcome, he said.
The contributions of the pharmaceutical industry—and appreciation for those—has been another lesson learned, Hepburn said. “The most important thing I have to say is what you do matters very deeply for what we are trying to do to prevent or mitigate the next pandemic,” he said. Another lesson learned: the highest quality products need to be made at speed—the better this is done, the more outbreaks can be mitigated and millions of lives can be saved in the future.
Manufacturing innovation is an area where the White House has but energy, including the development of the American Pandemic Preparedness Plan Annual Progress Report, which last year included updates on COVID-19, seasonal flu, monkeypox, and the Sudan virus disease outbreak in Uganda. His office completed its first progress report in September 2022. He encouraged attendees to review the report and see how much manufacturing innovation is included.
He hopes to change the fragmented nature of multiple government agencies working on initiatives to be able to move more quickly with innovative concepts through early partnerships to de-risk the technology, partner with the private sector on early stages, and move forward quickly as needed, much the way the government was able to do with Operation Warp Speed and the other things done collectively for the pandemic.
Hepburn observed that pivoting is one of the biggest challenges; as an example, the global community needs to determine whether billions of doses of vaccines need to be made as we go forward for COVID-19, which is still a pandemic and will still present challenges. Can the capacity be shifted to other vaccines that could prevent diseases in a steady state, to address diseases such as measles, HPV, and hepatitis B? Looking forward, he said perhaps antibodies, small molecules, even cell and gene therapy could be part of applying what was done for the pandemic for the future good. The pharmaceutical industry’s role in moving forward, he said, is how to manufacture with speed, scale, quality, and reduced costs. “We really need solutions,” he said.
Hepburn gave overviews of several programs that are working to support innovation:
- Manufacturing USA started about 10 years ago; it involves investment in industries in precompetitive spaces, encouraging innovation and de-risking. Initiatives in the pharmaceutical industry include the NIIMBL consortium.
- BARDA Ventures works with venture capital to drive promising products: it facilitates partnerships for quick, agile investment decisions, crowd-in private capital, and de-risk commercialization of transformative technologies that help prepare for future pandemics. BARDA collaborates with Global Health Investment Corp to address gaps in health security.
His request to the pharmaceutical industry: “Be super flexible. I know there is interest in doing that.” Being able to switch between products and scale when there is an outbreak, and working with regulatory agencies to support these efforts, is key.
Jessica Ballinger, President and Chief Operating Officer, Lyndra Therapeutics, gave the next keynote on 31 January on “Innovating to Reinvent Medicine for a Healthier World.” She talked about the work of Lyndra, a 125 person company that has made great strides in just 10 years.
Her presentation focused on medicine issues rather than pandemic issues, speaking to areas of change that are transforming how medications are delivered to patients. Ballinger discussed challenges with daily pills, where improved delivery of medications could have the biggest impact, and what technical innovations are needed to reinvent medicine.
Most patients struggle to adhere to daily pill taking, which can result in missed doses when people forget to take their pills, especially with multiple doses per day. This is a particularly challenging issue for
schizophrenia and bipolar patients who self-report the highest levels of struggle with adherence. Ways to address this are needed, since medications won’t work if they are not taken, especially with chronic diseases.
Her company decided to explore long-acting oral medications that are delivered once a week instead of daily, with the goals of staying in the therapeutic area, with consistent delivery, and better health outcomes with fewer doses.
The company developed the LYNX drug delivery platform with a gastric retentive capsule that delivers medications and pieces exit safely into the intestine as segments of the medications are released.
Malaria prophylaxis, high blood pressure and cholesterol are examples of treatment areas that can work well. For the latter two, some medications can be combined for cardiovascular treatment with less frequent dosages, which helps ensure older patients who may struggle more with maintaining a drug taking schedule receive the medications needed to manage the condition. Drug addiction prevention and oral contraception are other areas of interest. For schizophrenia, she noted, there is significant unmet interest since it is very important to stay on therapy to reduce hospitalization and relapse.
The company is using continuous manufacturing with a fully automated commercial line under construction, and developed its technology via animal testing and the use of an artificial stomach to test how the products work within the stomach. She said that 10 people have been dosed and they do have 14-day resonance.
Cost of Capital
James Stephanou, Vice President, Global Engineering Solutions, Merck, presented on “Cost of Capital for Facilities of the Future,” the final morning keynote on 31 January. Citing the Merck tagline, “medicine is for the people,” Stephanou said that medicine needs to be affordable globally, so the industry needs to think about how to make products affordable for more people.
Delivering quickly to patients, and doing two of the three traditional triangle factors well –schedule, cost, and quality—means that the third part of the triangle will follow. In considering cost, facilities of the future has to be “FAF:” flexible, affordable, and fast. Cost drivers are research and development, supply chain, OPEX (operational expenditure), and CAPEX (capital expenditure). Stephanou noted that the pharmaceutical industry spends 20% to 25% of revenue on R&D, which I significant. Cost drivers leading to FAF are redundancy, standard equipment and systems, and prefabrication. A lot is spent to be reliable; building reliability will save on the costs of redundancy.
Costs for standard equipment and systems have been a struggle. Ways to address this, he suggested, include working with vendor engineering instead of doing it ourselves, catalog shopping before bespoke design, and buying a little bigger because it will be cheaper in the long run and will not require engineering. Prefabrication can also help. It is important, he said, to think not just about what you are making now, but what you might make and how you can pivot.