From The Editor | August 19, 2019

Inside NIIMBL And Its New FDA Partnership

Matt Pillar

By Matthew Pillar, Editor, BioProcess Online

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Last month, the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) announced that the University of Delaware, on behalf of NIIMBL, has entered into a Collaborative Research and Development Agreement (CRADA) with the FDA. Effective July 15, the agreement gave FDA and NIIMBL the ability to “collaborate in a pre-competitive environment to strengthen research, innovation, training, and collaboration in the biopharma manufacturing industry.”

That’s a whole bunch of potentially hollow platitudes in one line of PR-speak. After reading the official announcement of the partnership, I sought to learn more about the Institute and its goals, how it’s funded, who’s keeping score on progress, and what its newly-expanded partnership with the FDA would bring to the table. So I sat down with Kelvin Lee, Gore Professor of Chemical and Biomolecular Engineering at the University of Delaware and institute director at NIIMBL.

Lee’s expertise is largely in the upstream end of bioprocessing. He helped sequence the CHO-K1 and Chinese hamster genomes, which the University maintains as an open reference genome for the community. Most of his work is related to host cell proteins, cell line development, and cell line stability.

Outside of the lab, Lee is an aggressive advocate for the power of community in biopharma. He and his team are reasonably well known in the proteomics, genomics, and systems biology communities, a perspective that lends itself to serving as the catalyst that brings those communities together. As such, Lee helped lead the formation of the National Science Foundation center known as AMBIC (Advanced Mammalian Bio Manufacturing Innovation Center). That center, also focused primarily on upstream cell line development technology, is comprised of five universities and more than  two dozen biopharma players.

THE ORIGINS OF NIIMBL

For its part, NIIMBL came together quite recently, with a March 1, 2017 launch. At present, the effort is funded in large part by the National Institute of Standards and Technology (NIST), which is part of the U.S. Department of Commerce. Leading into 2012, the federal government was looking broadly at issues related to advanced manufacturing, technology, and employment in the U.S.  One outcome of that contemplation was the creation of what’s known today as the Manufacturing USA Network of Institutes, which currently includes 14 institutes, each representing a different sector of the economy. NIIMBL represents Biopharma, while the Department of Defense funds eight separate industry-specific institutes and the Department of Energy funds five.

Each institute brings together universities, community colleges, nonprofits, small businesses, suppliers, manufacturers, and state, local, and federal governments and government agencies relevant to the sector. The goal is to bring these stakeholders together to pursue development and maturation of technologies by investing skill and resources in a technology or project, or in the case of biopharma, an assay. But there’s a caveat; the tech, project, or assay, as it were, has to have reached a specific point of maturation where it’s established in proof and principle, but not yet “de-risked” to the point that it appears in commercial products or processes.

“We’re trying to push technologies and advance them across what's sometimes called the ‘valley of death’ by having multiple stakeholders co-invest in their development,” explains Lee.

Interestingly, the collaborative environment isn’t limited to “intramural” activity within a specific sector. The Manufacturing USA initiative is designed to encourage “extramural” collaboration. “If we're going to pursue something in NIIMBL that's related to robotics, for example, we wouldn't have to have robotics companies and expertise inside of our institute. We would collaborate with the corresponding institute,” explains Lee.

The technical scope at NIIMBL is essentially anything where biology is important in the manufacturing of a drug product. “In scope for NIIMBL are therapeutic proteins and mAbs as well as vaccines, cell therapies and gene therapies,” says Lee. “We do stop where the cell is maybe the starting material for a future drug product, such as a tissue engineered construct, or an organ. That’s the domain of a sister institute [Advanced Regenerative Manufacturing Institute / Bio Fab USA]. But we are in scope for gene therapies and CAR T-cell immunotherapies, for example.”

WHAT THREATENS INNOVATION IN BIOPHARMA?

It takes a village of stakeholders to push advances across the valley of death, according to Lee, because this is such a risk-averse industry. “I think most people would agree that this industry is marked by a conservative culture,” says Lee. “When bioprocess decision makers think about whether their company is going to adopt or implement a new technology as part of a process, their first inclination is often to say, ‘let's not be the first one to do this.’”

But perhaps ironically, that same aversion to progressive decision making on the part of individual companies supports the very notion of the collective industry endeavors Lee promotes. “It’s difficult to make a good business case for pushing a new technology into the process when the company is concerned about getting to market, profits, and timelines. The last thing you want is to have some time-to-revenue-risking, back-and-forth question-and-answer session with, for example, the FDA.”

Even post-FDA approval, in today's global environment, biopharma companies are unlikely to gain approvals from all the geographies in which they play in a timely manner. That poses a particular challenge, as once a product is launched, it’s very hard to accept the prospect of a process change. And yet, Lee argues that there’s not a very strong business case for new technologies in the space. That’s where he says NIIMBL delivers value to the community by offering a collaborative venue to identify the high-priority and potentially important technological advances coming down the pike. “We can collaboratively design the studies, collect the data, mature the technologies, refine them, and publish the results. Ultimately, our members and the government, whether the FDA or NIST or NIH, can access that data to inform their understanding of how that technology or that assay perform.”

NIIMBL FUNDING, ORGANIZATION, AND PROGRAMMING

NIIMBL is effectively a $250 million public/private consortia that’s funded over a five-to-seven year period. The organization’s current funding is comprised of $70 million from NIST, and another $180 million from its 120 member organizations. Membership is primarily industry, academia, and nonprofit organizations. The largest portion of its resource allocation goes toward technology and workforce/talent development projects. “Twice a year, NIIMBL puts out a request for proposals calling for technology project ideas or workforce training related ideas. We then go through a process to identify and vett projects to find those that are most relevant to the industry,” says Lee. Then, NIIMBL opens the project up to a contracting process to align appropriate member stakeholders. “Our typical projects involve anywhere from two to five partnering organizations, who are given a 12- to 18-month timeline to execute. Typically, the budget will be between $1 million and $2.5 million per project over that time period,” he says. Projects span from technologies related to the drug substance or product manufacturing processes to process control practices, and can range from vaccines to antibodies to gene therapy vectors to cell therapies.

NIIMBL training programs are heavily focused on operations professionals. To date, the organization has authorized some 15 training programs around the country. It also hosts workshops on technology, workforce development, diversity, and inclusion, and it has published roadmaps on vaccines, gene therapies, ADCs, and bispecifics. “Those roadmaps help also provide some context for where the higher priority needs of the industry are,” says Lee. “We invite the broad community to participate, and we've had good engagement from inside and outside of NIIMBL, from government agencies, and from the private sector.”

The organization hosts an annual meeting, which includes a forum that’s open to the broader biopharma community. Finally, NIIMBL facilitates a regulatory considerations committee that brings the industry together to investigate and discuss new technologies and regulatory science issues in a forum that didn’t previously exist. “It's partly about having conversations, but it's also potentially about executing projects to collect data that supports the answers to the questions that come up,” explains Lee.

ACCOUNTABILITY AT NIIMBL

Lee doesn’t dance around the accountability question. NIIMBL is ultimately funded in part by tax dollars, and when asked who’s ultimately judging the success of this grand experiment, he tells me it’s NIST, a subsidiary of the Department of Commerce (DoC). “They’ve effectively issued a contract to us, and they have very certain expectations relative to our performance. “The DoC is obviously focused on the country’s economic activity, so to the extent that we're able to support biopharma-related economic activity and ensure an appropriate workforce is accessible to the industry, then I think we'll be doing what we are supposed to be doing,” says Lee, before offering up a more nuanced response. “I think perhaps a more important view of this is that we're a membership organization comprised of companies, universities and public and nonprofit organizations that pay a membership fee to be able to benefit from the technology advancements, initiatives and activities we produce,” he says. “Companies that join and fail to see value are not going to continue to stay with NIIMBL. So, at the end of the day, we're accountable to our members and delivering value to them. I think that's probably the more important answer.”

WHAT’S NEXT FOR NIIMBL AND THE FDA

While the organization is quite dependent on its government charter at present, Lee’s vision for NIIMBL sees the institute weaning itself from federal dependence as part of its go-forward plan. “The law Congress passed to authorize our creation actually talks about how each institute is supposed to have a plan for its own financial sustainability in the event that the federal funding goes away,” explains Lee. “We’ve structured ourselves to be viable post-NIST funding, and that's the membership model, where organizations are committing resources to NIIMBL in exchange for being able to engage in our programming.”

That’s not to say that Lee is anxious to cut the cord, and it’s not likely he’ll have to. The institute’s success suggests it won’t be a candidate for defunding. Several of the associated 14 institutes have received second rounds of federal funding, specifically those that have found success securing the financial sponsorships of private enterprises.

NIIMBL’s recently-announced CRADA with the FDA might further cement its attachment to the federal government. The Institute has enjoyed a high-level framework agreement with the FDA for more than a year, which has informally facilitated its interaction with the FDA. The newly announced partnership agreement expands on that by formalizing a framework to streamline the FDA's participation on NIIMBL projects at the scientific level. “This will give their scientists an avenue to be more engaged with our NIIMBL project teams, and it will make it easier for FDA scientists to pitch project ideas that they consider high-priority. This is a key element of the partnership, because FDA scientists have a very different perspective than academic—and even NIST—scientists,” explains Lee.

More specifically, the CRADA will support investments in regulatory science research and training, in an effort to foster advanced manufacturing innovations in trending areas including continuous manufacturing, on-demand manufacturing, and advanced process control technologies, among others. Ultimately, the Institute hopes these advancements will increase its impact by enhancing patient access to new and improved medicines. “We are increasingly seeing the potential for advanced manufacturing innovations that can improve drug quality, help address shortages of medicines, speed time-to-market, and support personalized medicine through technologies including 3D printing and continuous manufacturing,” said Acting FDA Commissioner Ned Sharpless, M.D., in a prepared statement. “These technologies can also help the U.S. prepare for public health emergencies by rapidly scaling manufacturing capabilities for vaccines and other medical countermeasures. FDA is taking many steps, including this public-private partnership with NIIMBL, to encourage and help realize the potential of advanced manufacturing: issuing guidance on emerging technologies, approving products made with these technologies, and advancing regulatory science.”

Lee adds that NIIMBL is an inclusive and growing community. If you’d like to learn how your organization can get involved, request membership information here.