Left to right, panelists Ninette van Lingen, Sundar Ramanan, and Brad Stewart, with moderator Dan Stanton

During the 2024 BIO International Convention in San Diego, CA, Dan Stanton (editorial director at Informa Connect Life Sciences) moderated a panel of experts from biotechnology companies who addressed ongoing news in biomanufacturing and how recent developments in the space stand to affect the industry. Stanton was joined by Ninette van Lingen (senior vice president in business development at Just–Evotec Biologics), Sundar Ramanan (chief quality officer at Enzene), and Brad Stewart (national leader for life sciences at BDO USA).

COVID Market Fluctuations

Stanton led the discussion by reflecting on how biomanufacturing demands spiked during the COVID-19 pandemic. Business rose for many suppliers and contract development and manufacturing organizations (CDMOs) before demand normalized 18 months ago, leading to a general decline. Stewart acknowledged the difficulty that such a shift caused for many companies.

“Those of us who’ve been in this industry for a long time, we see these cycles, boom and bust.” He added, “I was running a company in 2008, and literally capital went away overnight. We’ve seen something similar here.” He explained that investment reached abnormal heights during the pandemic, and as a result, capacity built for vaccine manufacturing has fallen into disuse. But he pointed out that the market is shifting back toward customers, enabling CDMOs to get funding again.

“The seed money is starting to loosen up,” van Lingen agreed. “There’s a lot more focus on specific therapeutic indications and streamlined therapies, which is a nice approach as we’re coming out of COVID.”

Stewart added that cyclical markets in biopharmaceutical manufacturing reflect problems that other industries have faced, such as the electric-vehicle market, the technology industry, and the dot-com bubble that burst a couple decades ago. But he pointed out that in biotechnology specifically, “timelines are so much longer, and frequently we’re competing for capital. It’s not uncommon to have life-sciences investors who also invest in technology. How can you ever justify that investment in a 15-year or 10-year development program when your partner invested in Google 15 years ago?”

Ramanan added that money was easier to come by during the pandemic and that companies were funding ideas that they otherwise would not have. “Those inefficiencies are now removed from the system,” he said, adding that supply chains have stabilized, except for a few raw materials that remain difficult to source.

Localized Manufacturing

Stanton pointed out that Just–Evotech and Enzene have facilities in the United States, with the former company scheduled to open a new building in France later in 2024. He asked the panelists about the importance of localized manufacturing and the rationale behind building at their chosen sites.

The panelists agreed that global access to medications is an important goal for biomanufacturers. Ramanan said that Enzene started in India and created fully connected continuous manufacturing (FCCM) to serve Indian patients. He pointed out that US biosimilar drugs struggle to reach much of the global population, and thus, Enzene played a role in filling an unmet need for Indian patients. His company plans to bring its same continuous manufacturing technology to the United States. He added that through quickly building facilities, his company is able to “bring the value of the technology and intensification to patients much faster.”

Bracing for a Future with the BIOSECURE Act

Stanton asked panelists about how the US BIOSECURE Act stands to affect the global biomanufacturing industry. During the BIO convention, the text of the legislation was still under revision. If passed, the act will restrict partnerships with Chinese CDMOs by 2032 due to concerns about intellectual property (IP) theft and biodefense.

“The BIOSECURE Act [would create] significant challenges to our supply chains,” Stewart said. He added that certain technologies and raw materials are specific to certain regions and that it wouldn’t be feasible to move seamlessly away from existing facilities that have extensive licensing and validation along with highly skilled workers. “If you’re already working with a CDMO somewhere in the world, then your processes are set up, you’ve done all the tech transfer, [and] you’re actually producing clinical supply.”

Van Lingen agreed, adding that it is important to educate policymakers about the needs and concerns of the biopharmaceutical industry so that stakeholders can agree on a common-sense approach to biosecurity. She said that geopolitical factors are spurring an increase in companies that are seeking capacity around the globe. “I think that over the next three years, we’ll see a balancing out of where that ends up, but right now we’re not really concerned.”

Changes in the Industry

Companies have turned to continuous manufacturing to improve efficiency and alleviate some of the difficulties with capacity. “The great thing about continuous manufacturing is that the footprint is small and your yield is big,” said van Lingen.

Ramanan emphasized the need to serve patients and curate talent, regardless of geopolitical concerns. Stewart agreed, citing talent acquisition and retention as the biggest challenge. “Forget the facilities. You just don’t have the talent to run it.” But he also added that a number of changes have affected biomanufacturing, such as the switch to single-use systems, the general scale-down of bioreactor sizes, and process improvements.

He added that new product modalities such as cell and gene therapies (CGTs) have helped to inspire change in an industry that is traditionally averse to it. “It’s not just about increasing yield and increasing titers anymore. It’s about placing these technologies within an ever-changing world, politically and economically.”

Acquisitions and Investments

Stewart addressed the potential acquisition of Catalent by Novo Holdings, the sale of associated fill–finish plants, and growth in the demand for glucagon-like peptide 1 (GLP-1) products that companies such as Novo Nordisk develop. He said, “If you knew the future, you probably would’ve been building antibody–drug conjugates (ADCs) and maybe facilities to fill–finish GLP-1s.” He said that such developments are unpredictable and that companies are scrambling to increase capacity to limit revenue loss. He cited investments from Novo Nordisk and Eli Lilly, both of which are working to expand production.

Ramanan added that capacity is both a chronic and acute need. He emphasized that it takes two to three years to build a new facility, whereas new technologies such as those for continuous manufacturing can produce faster results. “Adapting and moving to fully connected continuous manufacturing can address those needs.” He added that with the right processes, “you triple the capacity pretty fast.”

Stewart agreed, adding, “Fill–finish is a massive shortfall right now.” He said that industry leaders were unable to project the sudden popularity of an injectable GLP-1 drug. “You see the impact it has further along in the research and development (R&D) pipeline. Now the holy grail is an oral GLP-1.” He said such a development could prove difficult for companies that invest billions of dollars in the injectable version, which is a market that could then dry up.

From her perspective as a monoclonal-antibody (mAb) manufacturer, van Lingen added, “This is a boon for the organizations that have made investments in this classification of drug.”

The Political Future

Stanton asked the panel how the upcoming election in the United States could affect the CDMO space. Stewart noted that both Trump and Biden had supported drug price controls, which were enacted in the Inflation Reduction Act (IRA). He suggested that changes will come to the IRA regardless of who is elected president in 2024 to address the exclusivity differences between large- and small-molecule drug products. “We’re already seeing the negative effects of people moving away from oral drug development, particularly in oncology.”

Van Lingen again emphasized the need to educate policymakers, this time on the ramifications of the IRA in terms of its long-term impact on R&D. “There are short-term goals that they’re shooting for,” she said, “but there’s a lack of understanding [about] the long-term ramifications of those decisions because they’re using the political play on everybody’s wallet.”

She emphasized that industry professionals are concerned about the political future. “I can have a conversation about reimbursements, but people aren’t really peeling back the onion and having the real discussion about what will happen 10 years from now because of the changes R&D tied to all of that.”

“In terms of industrial policy,” Ramanan added, “we should be mindful about confusing causation and correlation.” But he added that new policies take time to enact and meaningful changes will not happen right away. “The free-market–enterprise system that we have in the United States allows for things to work themselves out.”

Josh Abbott is associate editor of BioProcess International; [email protected].

Watch Online

See all panel discussions online from BPI Theater at BIO 2024.