Pharma Manufacturing _ March 2025

Four CDMOs redefining what it means to outsource

Revolutionizing early-stage drug development with rapid genes Overcoming enzyme manufacturing challenges March 2025

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table of contents

VOLUME 24 / ISSUE 1

Andrea Corona

Senior Editor

Greg Slabodkin Editor in Chief

Global Footprints

Four CDMOs redefining what it means to outsource

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FEATURES automation & control

drug development

supply chain

Automating liquid-filled vial nasal delivery

Revolutionizing early-stage drug development with rapid genes

Overcoming enzyme manufacturing challenges

Best practices for designing automated machinery solutions for bringing nasal devices to market

Faster turnaround times on gene assembly and verification are allowing researchers to do more

Therapeutic enzymes are driving drug development, but scaling remains challenging

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COLUMNS & DEPARTMENTS 5 FROM THE EDITOR

D I G I TA L

EDITION

6 INDUSTRY DOSE

33 TAKING STOCK

34 FINAL DOSE

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32 ENGINEERING ANGLES

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from the editor Greg Slabodkin Editor-in-Chief

EDITORIAL TEAM

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andrea corona

Will 2025 be a good year for CDMOs? The outlook for the outsourcing space is cautiously optimistic

Senior Editor acorona@endeavorb2b.com EDITORIAL ADVISORY BOARD BIKASH CHATTERJEE, Pharmatech Associates EMIL CIURCZAK, Doramaxx Consulting ROBERT DREAM, HDR Company BARRY HOLTZ, Phylloceuticals ERIC LANGER, BioPlan Associates IVAN LUGO, INDUNIV, Puerto Rico GIRISH MALHOTRA, Epcot International RICH MYER, Tergus Pharma GARY RITCHIE, GER Compliance MICHAEL TOUSEY, Solid Dose Technology DESIGN & PRODUCTION TEAM

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Contract development and manufacturing organizations (CDMOs) are more critical than ever to the biopharmaceutical industry, providing essential outsourcing services to customers and helping them to focus on their core strengths.

With fewer biopharma companies performing all of their manufacturing in-house, CDMOs provide much-needed, at-scale production capacity, as well as outsourced services such as drug development and testing to reduce costs and tap outside expertise. From preclinical to phase III and commercial manufacturing, contractors continue to show their value as the industry has recovered from the COVID-19 pandemic supply-chain pressures and other challenges.

While CDMOs faced headwinds in 2024, the outlook this year for the outsourcing space is cautiously optimistic based on the biopharma industry’s funding levels, product pipelines, and R&D spending.

“A significant rebound in M&A activity this year would be a welcome tailwind for sentiment around the large pharma space, particularly if these transactions help offset declining revenue from key products due to loss of exclusivity over the next few years,” according to Max Smock, equity research analyst at William Blair. Smock contends that, in addition to potentially providing larger innovators with more flexibility to spend on R&D, an uptick in M&A activity “ could also help end the biotech slump that weighed on demand for pharmaceutical outsourcing and services companies in 2024.”

However, looking at 2025 and beyond, it’s no surprise that the global CDMO market is expected to grow from $136.6 billion in 2024 to $191.6 billion by the end of 2029, at a compound annual growth rate of 7% over that timeframe, according to the latest study from BCC Research.

Among the factors contributing to the growth of the CDMO market is increasing demand for advanced therapeutics such as biologics and gene therapies to treat complex diseases and improve patient outcomes, as well as services like active pharmaceutical ingredient (API) manufacturing, drug production, and regulatory support.

In this issue, we profile four CDMOs with global footprints that are positioned for growth in their respective markets. One of those companies is Recipharm, with 17 facilities in 10 countries, which prides itself on having a global presence with local expertise.

Recipharm’s revenue last year — nearly $1 billion — grew in high-single digits and the company signed more than 100 biologics contracts.

While this year some CDMOs will no doubt see an improving picture for their businesses, others will still feel the pinch of softness in demand for their services as they navigate a rapidly evolving landscape. The good news is there are meaningful signs of recovery in the sector and the long-term growth drivers for the industry remain strong. 

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Andrea Corona Senior Editor

2025 pharma predictions

From manufacturing to supply chain strategies, here’s how drug manufacturers are looking at the year ahead

Pharma stands at the threshold of 2025 with a blend of cautious optimism and strategic urgency. Scientific breakthroughs, regulatory shifts, and technological advancements continue to reshape the sector, forcing companies to adapt to new realities.

From cutting-edge drug delivery systems to AI-driven research models, the coming year will demand agility, innovation, and forward-thinking strategies. As geopolitical uncertainties and supply chain disruptions persist, companies are sharpening their focus on operational resilience, regulatory efficiency, and next-generation manufacturing solutions.

Emerging therapies such as antibody-drug conjugates, bispecific antibodies, and cell and gene therapies are pushing the boundaries of medicine, creating new challenges in development, scalability, and regulatory approval.

Meanwhile, advancements in 3D printing, modular manufacturing, and AI-driven pharmacovigilance signal a shift toward more efficient and precise drug production.

The industry’s ability to integrate these innovations into existing workflows will determine how quickly groundbreaking treatments can reach patients.

Regulatory trends will also play a pivotal role in shaping 2025. Simultaneous global submissions, streamlined safety reporting, and evolving compliance frameworks will redefine how drugs move from discovery to market. Companies investing in digital transformation, automated quality assurance, and AI-assisted data processing will gain a competitive edge, reducing inefficiencies that have traditionally slowed regulatory approvals. At the same time, sustainability and ethical sourcing will remain top of mind as drugmakers navigate the intersection of innovation and responsibility.

To provide a comprehensive outlook on what’s ahead, we’ve gathered insights from leaders across the industry.

Their predictions offer a glimpse into the trends, challenges, and opportunities that will shape biopharma in 2025. From manufacturing and supply chain strategies to scientific breakthroughs and regulatory evolution, these perspectives illustrate how companies are preparing for the next phase of pharmaceutical advancement.

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Modular manufacturing for complex modalities

“The growing prominence of antibodydrug conjugates, bispecific antibodies, viral gene therapies and other complex modalities in 2025 will amplify the need for innovation in development and manufacturing. By emphasizing product attributes rather than the process itself, modular manufacturing drives greater productivity, flexibility and cost efficiency. Modular units enable us to further optimize and adopt new technologies post-commercialization.

As the adoption of modular manufacturing continues to expand, we are actively enabling this transformation, and we remain committed to innovative reagents and single-use technologies that will improve processes in the future.

Together, we can unlock the full potential of modular manufacturing for complex modalities to boost efficiency and improve product quality.”

— Benoit Gourdier, Executive Vice President, Bioscience Production, Avantor

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The rise of cellulose-based capsules

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“In 2025, advancements in manufacturing technology and polymer science are revolutionizing the capsule industry, driving the widespread adoption of cellulose-based capsules. These innovations address raw material concerns, enhance API release and stability, and offer formulators significant advantages. As the limitations of gelatine become increasingly evident, scientists are leveraging modern technologies to optimize product development and adapt to shifting market demands.

The adoption of cellulose capsules continues to grow significantly. While costs may pose challenges, the industry’s focus on rapid market entry and first-time-right development underscores the advantages of vegetarian alternatives, which provide superior properties and reliable performance.”

— Dr. Subhashis Chakraborty, General Manager, Head Global Product Management, ACG Capsules, ACG

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AI and the future of pharmacovigilance

“In 2025, pharmacovigilance will undergo a bold transformation as AI and machine learning move beyond buzzwords to become the backbone of proactive safety management, reshaping how the pharmaceutical industry engages with real-world data and patient outcomes.”

— Ana Pedro Jesuíno, Associate Director of Marketed Product Safety, IQVIA SRC team

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Quality assurance and AI integration

“Although quality assurance (QA) and quality control (QC) business processes are connected, the legacy systems underpinning them are not. To address this challenge, leading companies are connecting QA, QC, and partners through a common technology. In 2025, this investment in digital quality will shorten testing time and accelerate time to market.

Quality organizations will unify their data and applications to significantly advance their reporting and analytics. This will deliver metrics to proactively manage risks and identify and address bottlenecks early. For example, having QA and QC data available at the batch decision point will result in faster batch release. Working from a single source of data will standardize collaboration with partners, eliminating manual work and the risk of data errors.”

— Ashley McMillan, Senior Director, Vault LIMS Strategy, Veeva

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AI-driven drug discovery and the lab-in-a-loop model

“For AI to make a meaningful impact in life sciences, the drug discovery process must evolve into a Lab-in-a-Loop model. In this model, R&D and clinical data from various applications, databases, and lab equipment are ingested, centralized, and used to create predictive models for guiding the next set of experiments.

While traditional workflows are often viewed as linear, this approach requires flexibility to integrate new insights as they emerge from ongoing experiments.”

— Christian Olsen, Associate Vice President, Dotmatics March 2025 / PharmaManufacturing.com

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Citeline’s Biomedtracer projects that the FDA is expected to grant nearly 70 approvals and label expansions in 2025.

AI-powered drug discovery to improve clinical success

“In 2024, the biotech sector faced significant funding challenges, but VeriSIM Life has been at the forefront of demonstrating how a biology-first AI approach can derisk early-stage assets and increase the likelihood of clinical success.

Our platform’s ability to simulate complex biological systems and predict drug outcomes with high precision is not just an innovation—it’s a necessity for navigating the challenges of modern drug discovery. The next wave of biotech innovation will come from data-driven insights, and our hybrid AI approach is leading that charge.

As more pharma companies and investors look to data for making smarter, more predictive decisions, VeriSIM Life’s proprietary biological models and AI simulations will become indispensable tools for reducing development risk and unlocking new opportunities.”

— Dr. Jo Varshney, CEO and Founder, VeriSIM Life

3D printing’s role in drug delivery

“3D printing is poised to revolutionize oral solid drug delivery systems, bringing precision, personalization, and innovation to the forefront of pharmaceutical development. This technology meets the growing demand for customized therapies, enabling tailored doses, intricate geometries, and advanced drug-release profiles.

Notably, it facilitates the delivery of highly potent drugs, such as anti-cancer treatments, by balancing efficacy with minimized toxicity.

By supporting controlled, delayed, and immediate drug-release mechanisms, this technology optimizes treatment regimens. As regulatory bodies adapt to these advancements, 3D printing will reshape the future of oral solid delivery systems, offering more personalized, efficient, and patient-centric healthcare solutions.”

— Dr. Jnanadeva Bhat, Vice President, Head – Formulation R&D Pharma and Nutra, ACG

The future of cell therapies for solid tumors

“In 2024, we witnessed historic breakthroughs in cancer treatment with the FDA’s approval of the first cell therapies specifically for solid tumors. The approvals of Amtagvi for metastatic melanoma and Tecelra for metastatic synovial sarcoma mark a significant milestone in the development of personalized treatments for various types of solid tumors. These advancements underscore the progress being made in cell therapies and highlight the urgent need for innovative strategies and strategic technology collaborations to tackle the complexities of targeting solid tumors.

Advanced licensing platforms and techniques are crucial to ensure robust production and scalability. The current funding landscape makes it unlikely that many cell therapy biotechs will have the capital to make investments on their own. Leveraging manufacturing models that prioritize proximity to patients and incorporate advanced technologies is vital for the efficient development of cell therapies for solid tumors.”

— Jason Bock, Co-Founder and CEO, CTMC

Simultaneous submissions will speed approvals

“Once a practical reality, sequential submissions should now be seen as an outdated obstacle to getting medicines to patients faster.

Regulatory veterans will remember the not-so-distant past when submissions were shipped to health authorities in trucks full of documents. Even with digitalization, the volume and complexity have persisted. Regulatory teams still take a largely sequential approach, seeking approval in core markets first and then moving to others over time. This process leaves patients in downstream markets – often smaller and underserved – waiting longer for new medicines.

New methods like active dossiers, which represent the outcomes of complex submission processes, will let teams use prior submissions faster and more easily. Submission processes that once took five years or more will take fewer as more companies and health authorities invest in closing the gap to simultaneous submissions.”

— Marc Gabriel, Vice President, Vault RIM

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ADC manufacturing and supply chain challenges

“Antibody-drug conjugates (ADCs) will continue to be of great interest to biotech and pharmaceutical companies for targeted cancer therapies. However, the manufacturing processes for ADCs present several challenges. Since ADCs consist of an antibody, a cytotoxic payload, and a chemical linker, companies tend to rely on different vendors for each component, complicating the supply chain.

Biotech and pharmaceutical companies are overcoming these challenges by partnering with contract organizations that have specialized facilities for ADC manufacturing and the analytical capabilities necessary to support every stage of ADC development and manufacturing. These contract organizations also strive to be one-stop shops for

ADCs, eliminating the need for collaboration among multiple vendors supplying each molecule component.”

— Songyoung Kim, Principal Scientist and Director of ADC Process Development, Samsung Biologics

Sustainabilty focus

“There are various ongoing trends in the pharma and CDMO sector that could be considered as ‘predictions for 2025’, including obvious topics such as artificial intelligence and machine learning integration, advanced technologies, and further diversification of therapeutic modalities.

To add my personal perspective, I am expecting – and hoping – to see ‘sustainability’ become a major theme.

Pharma companies must focus on reducing their environmental footprint;

for example, completely decarbonizing their own operations as well as their full supply chain (scope 1 to 3).

This will also be increasingly mandated by governments, consumers and investors.

I believe that CDMOs will continue to play a vital role as (integrated) partners for pharma/biotechs, in order to provide capacity, and – at least as importantly – provide expert knowledge and the required flexibility and speed to handle more diverse product requirements, including small batch sizes, quick scale ups, fast turnaround times and transfers and provision of specific solutions, that otherwise would not be available at all, or in the required time.”

— Hanns-Christian Mahler, CEO, ten23 health

In the 1950s, thalidomide was introduced as a sedative and quickly became popular for treating morning sickness in pregnant women. However, its widespread use was then linked to severe birth defects in thousands of babies, prompting its withdrawal from the market in the early 1960s. While the tragedy significantly impacted drug regulation and safety protocols worldwide, in the decades that followed, thalidomide found a remarkable second life in medicine. Research uncovered its effectiveness in treating conditions like leprosy and multiple myeloma, due to its anti-inflammatory and anti-angiogenic properties, and it was discovered that the drug belonged to a special new class of therapeutics: molecular glue degraders. This revelation, centered around thalidomide’s interaction with cereblon and other target proteins, catalyzed the exploration of similar molecules for targeted protein degradation. Since then, advances in the understanding of protein-protein interactions and the ubiquitin-proteasome system have propelled the development of new molecular glue degraders to target a variety of diseases. Despite their rocky origins, molecular glue degraders represent a landmark advancement in drug development, offering a novel approach to In the 1950s, thalidomide was introduced as a sedative and quickly became popular for treating morning sickness targeting and eliminating disease-causing proteins. These small, monovalent molecules, typically less than 500 daltons in size, in pregnant women. However, its widespread use was then linked to severe birth defects in thousands of babies, operate by inducing or stabilizing protein-protein interactions (PPIs) between an E3 ligase and a target protein. This interaction prompting its withdrawal from the market in the early 1960s. While the tragedy significantly impacted drug reguforms a ternary complex that triggers protein ubiquitination (where a ubiquitin molecule attaches itself to the protein), leading lation and safety protocols worldwide, in the decades that followed, thalidomide found a remarkable second life in to its subsequent degradation by the proteasome (the cell’s protein recycling system).Distinguished from PROTACs (proeolysis medicine. Research uncovered its effectiveness in treating conditions like leprosy and multiple myeloma, due to its targeting chimeras), molecular glues do not rely on bifunctional molecules linked to guide protein interaction. Instead, they work anti-inflammatory and anti-angiogenic properties, and it was discovered that the drug belonged to a special new by fitting snugly between protein-protein interfaces, enhancing the affinity between an E3 ligase and a target protein to initiate class of therapeutics: molecular glue degraders. This revelation, centered around thalidomide’s interaction with degradation. This crucial difference in mechanism highlights the unique advantage of molecular glues, which include their smaller size, higher membrane permeability, and superior pharmacokinetic properties. These attributes not only make molecular glues highly druggable but also offer a more versatile platform for developing new treatments. The seemingly sudden surge https://pharmamanu.podbean.com in interest and research surrounding molecular glue degraders can be traced back to their potent ability to target previously ‘undruggable’ proteins, a longstanding challenge in the pharma industry. This capability opens up new avenues for drug development, particularly in the treatment of complex diseases such as cancer, where traditional small molecule drugs and biologics have fallen short. Currently, only thalidomide and its analogues have been approved by the FDA. But with key players entering the ring and many clinical trials underway, the molecular glue garden is bound to bloom soon. From ancient tales of an elixir of life with the power to confer immortality, to stories of a mythical fountain of youth recounted around the world for thousands of years, to modern-day billionaires biohacking their bodies in an attempt to stave off death, humans have always had an obsession with/longevity.

For the pharma industry, the quest to live forever or stay eternally young has largely been viewed March 2025 PharmaManufacturing.com 9 as an impractical allocation of R&D resources. However, the need to increase humans’ overall healthy, productive lifespan has growing pharmacologic validity, especially because people are now living longer than ever before. By 2030, one in six people in

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GLOBAL FOOTPRINTS Four CDMOs redefining what it means to outsource Global reach has become a defining factor for CDMOs looking to stand out.

As pharmaceutical companies push for faster development timelines and more secure supply chains, they are turning to partners with the infrastructure and expertise to support drug manufacturing at scale.

At the same time, the industry faces pressure from all sides — economic uncertainty, supply chain disruptions, and shifting regulatory demands. Yet, CDMOs with a strong international presence are proving that strategic expansion and investment can help them stay ahead.

By building multi-site networks, strengthening regional operations, and broadening their capabilities, contract manufacturers are reinforcing their role as essential players in pharma.

This series highlights four CDMOs—Fujifilm Diosynth Biotechnologies, KBI Biopharma, etherna, and Recipharm—that have expanded their global footprints to support drug development and ensure reliable production for customers worldwide.

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cover story

Andrea Corona

Senior Editor

Greg Slabodkin Editor-in-Chief

KBI Biopharma: A science-focused partner built to solve KBI Biopharma didn’t set out to be a CDMO giant, it started with a centrifuge.

Not just any centrifuge, but a vertical, disposable model developed by Kinetic Biosystems Incorporated in Georgia.

Unlike standard models, which rely on a horizontal spinning motion that can create uneven sedimentation and require frequent cleaning, a vertical design allows for more uniform separation of biomaterials, improved fluid dynamics, and reduced shear stress — critical for delicate biologics.

The disposable aspect added another advantage, minimizing contamination risks and cutting down on turnaround time between batches. This early innovation set the tone for KBI’s approach: solve complex technical challenges with smarter, science-driven solutions.

By 2003, KBI had fully embraced its CDMO identity, and by 2010, it was expanding its mammalian production capabilities in North Carolina.

Today, KBI has six sites across North Carolina, Colorado, and Geneva, turning its early expertise in analytical problem-solving into a full-scale biomanufacturing operation.

Its specialty? Tackling the toughest molecules.

March 2025 / PharmaManufacturing.com

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Science first, always

From the beginning, KBI positioned itself as a science-focused CDMO, taking on molecules others couldn’t manufacture and creating custom solutions for complex proteins.

“We became well known for solving the toughest problems,” says Sigma Mostafa, Chief Scientific Officer. “A lot of our pipeline comes from customers who tried elsewhere and hit a wall. We built our reputation on getting those products across the finish line.”

KBI’s early years were defined by its work with first-in-human molecules—high-risk, high-reward projects that required deep technical expertise. That focus paid off. Many of those molecules have since advanced through late-stage development, with several now in commercial production.

Balancing early-stage innovation with commercial-scale execution is the next challenge.

“We had to shift from being just a problem solver to a full-spectrum CDMO,” Mostafa says. “Now, we’re not only accelerating biomolecules development but also seeing them through commercialization, which requires a different mindset and infrastructure.”

Balancing innovation with execution

As its portfolio expanded, KBI invested in building a seamless pipeline from early development to commercial launch, ensuring that molecules progress efficiently through every stage of their lifecycle. This shift required more than just additional capacity — it demanded smarter systems, streamlined operations, and a future-ready infrastructure capable of balancing the complexities of early-phase development with the rigor of commercial-scale manufacturing.

Key to that strategy is KBI’s proprietary digital platform, Program

View, a real-time data management and communication hub designed to eliminate inefficiencies across the development spectrum. Unlike traditional CDMO-client interactions, which often involve cumbersome email chains, scattered data reports, and time-consuming manual updates, Program View centralizes all project-related information into a single, accessible interface. “Everything, from lab data, client communication, regulatory reviews, feeds into one system,” Mostafa explains. “Customers can see real-time updates without the usual back-and-forth. It saves time and keeps projects moving.”

The system provides hands-free data transfer, automatically pulling processing equipment and analytical results through an integrated Electronic Laboratory Notebook (ELN). This reduces transcription errors, ensures data integrity, and allows for seamless integration of analytics into decision-making.

Clients can track progress live, minimizing the need for status update meetings and redundant reporting. The platform also consolidates quality documentation, facilitating regulatory submissions by ensuring that all necessary compliance data is stored, categorized, and readily available. By eliminating the inefficiencies of manual data handling, Program View enables KBI’s scientists to focus on innovation rather than administrative tasks, ultimately accelerating project timelines and reducing costs.

KBI has also been an early adopter of advanced processes and cell engineering technologies that set it apart from conventional CDMOs. KBI has also made significant investments in the antibody-drug conjugate (ADC) space, positioning itself as a leader in an increasingly vital area of biopharmaceutical development. ADCs represent one of the fastest-growing categories in oncology and other therapeutic areas.

“We have the chemistry expertise for ADC conjugation and are actively building capabilities for handling cytotoxic drugs,” says Mostafa. “By 2025, we aim to offer full process development for these complex molecules.”

Currently, KBI has extensive experience in ADC characterization and early-stage process development, including conjugation strategies that enhance drug stability and bioavailability. And on the cell line development front, KBI has pioneered

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cutting-edge cell line engineering strategies. KBI has developed a premium microbial strain and adopted a unique mammalian expression system inherited from/powered by Selexis.

By combining high-performing proprietary CHO cell line to strong vector design including unique genetic elements, Selexis platform ensures that each molecule produced at KBI is optimized for both efficiency and manufacturability. This translates into increased expression levels, improved protein fidelity and sustained cell line stability.

The company’s proprietary microbial platform, PureColi, for example, boasts five times the productivity of standard E. coli systems, enabling more cost-effective and scalable biologics production. For mammalian cell lines, KBI has developed advanced screening and selection techniques that enhance monoclonal antibody (mAb), multtispecific production and glycoprotetin, reduce unwanted mutations, and ensure high-purity protein output.

Through these strategic advancements — a fully integrated digital ecosystem, next-generation purification and cell engineering, and a deepening focus on ADCs — KBI is solidifying its reputation as a CDMO that doesn’t just manufacture molecules but optimizes and refines them from inception to commercialization.

By staying ahead of industry shifts and continuously improving its technological and operational framework, the company is ensuring that its clients’ molecules reach patients faster, safer, and more efficiently than thought possible.

Building the future

Looking ahead, KBI is also betting big on its in-house microbial and mammalian cell lines.

March 2025 / PharmaManufacturing.com

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“With PureColi, we can push productivity to new levels while maintaining quality,” Mostafa says. “It’s a game-changer for clients working in peptides and complex proteins.”

With a portfolio that spans first-in-human trials to commercial production, KBI isn’t just another CDMO—it’s a solutions provider for the toughest challenges in biomanufacturing. “We’ve built a model that works across the full lifecycle,” Mostafa says. “And we’re just getting started.”

Etherna: Refining RNA therapeutics In 2013, etherna went all in on a big idea: develop RNA-based therapeutics in an era when lipid nanoparticles (LNPs) were barely a footnote in drug development.

At the time, the industry was still relying on naked RNA, unprotected and vulnerable to degradation, as the go-to delivery method. etherna’s initial approach focused on ex vivo treatments, engineering cells outside the body before reinfusing them into patients.

Early work in melanoma immunotherapy using TriMix RNA showed promise, but the challenges of scaling ex vivo therapies, combined with limited market enthusiasm, made it clear that the company needed to rethink its delivery strategy.

“Even today, people are split between ex vivo and in vivo approaches,” says Bernard Sagaert, CEO of etherna. “But at the time, it was clear that for us to succeed, we needed a better delivery mechanism.” etherna turned its focus to direct intranodal injections, testing whether RNA could be administered directly to the immune system. The approach showed strong results in non-melanoma skin cancer, paving the way for a clinical trial in 2017, one that was ultimately cut short by the COVID-19 pandemic.

But the disruption also presented an opportunity. By this time, etherna had already begun investing in LNP-based delivery and had started developing its own lipid library. In 2022, the company took a decisive turn, and what emerged was a different kind of company — one that didn’t stop at RNA manufacturing but went above and beyond to fix the weaknesses in how it’s designed, delivered, and produced.

The pivot

While etherna worked on its RNA drug development, it also began exploring LNP technology to improve delivery.

At first, the company relied on licensed ionizable lipids, but this came with limitations. With a fragmented supply chain and increasing competition, etherna developed its own ionizable lipid library in collaboration with academic partners.

Then, in 2022, the company took a bold step. Key investors together with management redirected the business, “We made the decision not to focus on the clinic or do therapeutics anymore. Instead, we would focus

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on delivering cutting-edge enabling technologies and high-value services to advance drug development,” recounts Sagaert.

Instead of pushing its own drug candidates, etherna pivoted into a pure technology company, offering RNA quality optimization, LNP design, and scalable manufacturing solutions to partners. Sagaert, who had been with the company since 2017 as COO focusing on manufacturing, was named CEO to lead this transformation.

Rethinking RNA manufacturing

Even before etherna’s shift away from therapeutics, Sagaert had recognized a fundamental issue: RNA manufacturing remained stuck in an academic mindset. The processes used to produce mRNA were basic and inefficient, and much of the industry’s early upscaling efforts were built on these unoptimized methods.

“The way RNA was produced was really still academic, very basic,” Sagaert explains. “And those were the systems that got upscaled for the COVID vaccines. But we’ve focused on product quality.” etherna now refines every stage of the RNA manufacturing process, solving key industry bottlenecks: • RNA Purity and Scalability – etherna has improved the purity of its RNA, optimizing untranslated regions (UTRs) to enhance expression levels. “Improving UTRs can give a tenfold increase in expression,” Sagaert says. “That means reducing the dose tenfold, which immediately cuts costs.”

• Reducing Double-Stranded RNA (dsRNA) – High levels of dsRNA impurities are a known issue in mRNA therapeutics, triggering unwanted immune responses.

“We’ve reduced double-stranded

Bringing RNA to market isn’t just about speed, it’s about getting it right from the start.“ — Bernard Sagaert, CEO of etherna

RNA to extremely low levels ­and we’ve done it in the upstream IVT process, not downstream,” says Sagaert. “That means higher yields and lower costs without adding extra purification steps.”

• Batch Consistency – etherna works on scalable, cost-effective RNA production, ensuring that each batch maintains purity and potency.

Fixing the weak links in LNPs

RNA optimization is only half the equation. Lipid nanoparticles (LNPs) are the industry standard for delivery, but etherna believes they still have significant flaws.

“Most companies work on either RNA or LNPs,” says Sagaert. “But they don’t optimize them together. That’s a problem.” etherna has built an extensive library of 2,500 ionizable lipids, systematically testing their impact on delivery, biodistribution, and safety. The results speak for themselves.

“We’ve done in vivo assays showing a five- to tenfold increase in expression compared to ALC-0315 and SM-102,” says Sagaert, referring to the lipids used in approved mRNA COVID-19 vaccines. “Better targeting, better safety, better distribution.”

The company now has six LNP platforms, each tailored for specific applications; prophylactic vaccination, liver disease treatments, intratumoral cancer immunotherapy, and autoimmune modulation. Some of these platforms have already been tested in non-human primates, while others remain in earlier preclinical development. etherna’s focus is balancing potency, safety, and degradation, ensuring that each LNP platform is optimized for its specific therapeutic need.

Not a CDMO

etherna rejects the CDMO label. While it offers contract services, the company positions itself as a technology-first partner, integrating R&D, process development, and regulatory expertise to advance RNA-based medicines.

“We’re not a CDMO,” Sagaert emphasizes. “We reinvest everything into R&D. This is real innovation, not just manufacturing.” etherna’s end-to-end capabilities include: 1. RNA Design & Sequence Optimization 2. LNP Formulation & Lipid Engineering 3. Scalable CMC Process Development 4. Preclinical Pharmacology & Toxicology Support 5. Regulatory Strategy & Clinical Development Insights The company’s experience as a former RNA drug developer gives it a unique edge — it understands not just how to make RNA, but how to make it work in realworld applications.

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Going steady

etherna’s expertise has led to key partnerships, including Almirall and Dropshot.

With Almirall, etherna is developing a dermatology treatment using its LNP platform. “A year ago, we had a starting point,” Sagaert says. “Since then, we have leveraged etherna’s innovative proprietary mRNA capabilities and LNP formulations with Almirall’s leading expertise in medical dermatology to accelerate discovery of novel treatment options.” The Dropshot collaboration is focused on early-stage cardiac and renal therapeutics. “It builds on Dropshot’s prior evaluation of etherna’s mRNA and LNP platforms,” says Sagaert. “

Raising the bar for RNA

Despite the success of mRNA vaccines, the RNA field is still in its infancy — and etherna believes much of the current technology remains underdeveloped.

“There’s this assumption that, because COVID vaccines worked, the science is settled. It’s not,” Sagaert says. “We’re still figuring out quality control, optimizing LNPs, and making manufacturing more consistent.”

By integrating RNA quality, LNP technology, and scalable manufacturing, etherna is pushing RNA therapeutics beyond where they stand today. “Bringing RNA to market isn’t just about speed,” Sagaert says. “It’s about getting it right from the start.”

Fujifilm Diosynth Biotechnologies looks to leverage investments

Followng its $8B global manufacturilng investment, the CDMO is building identical large-scale production facilities in the U.S. and Europe Under a modular production model, global CDMO Fujifilm Diosynth Biotechnologies — which develops and manufactures biologics, vaccines and advanced therapies — is constructing identical large-scale facilities in the U.S. and Europe meant to seamlessly integrate manufacturing, regardless of location, for its customers.

In 2024, the company was “still very much in the planning mode of building this network we call KojoX, which is the Japanese name for facility and improvement,” CEO Lars Petersen told Pharma Manufacturing. Petersen said the CDMO’s facilities are designed, constructed, and ultimately will be operated as one worldwide network, which he contends “nobody’s really done before.”

Petersen, who took the helm as CEO in June 2023 and previously served in several executive roles in the company, is the driving force behind Fujifilm Diosynth Biotechnologies’ global ecosystem expansion that includes sites in Hillerød, Denmark, and Holly Springs, North Carolina. Since 2011, Fujifilm Corporation has invested over $8 billion to create the biologics manufacturing network, according to Petersen, who March 2025 / PharmaManufacturing.com

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acknowledged that there’s been “a lot of pressure” on its leadership as to when the investment will start to generate revenue.

Of the more than $8 billion investment in manufacturing, Petersen estimates that about $4 billion of that infrastructure will be “operationalized” by the end of 2025, finally adding “revenue streams” for the company.

“We’ve talked about this for a long time” but in November 2024 the CDMO opened the first KojoX node in the network in Denmark, Petersen said. The first phase of its expansion at the Hillerød site added six mammalian cell bioreactors, bringing the facility’s total current capacity to twelve 20,000L bioreactors, which the company claims will be the largest end-toend biopharmaceutical manufacturing site in Europe.

The next phase at Hillerød will include eight additional 20,000L bioreactors and two downstream processing streams, with fill/finish production slated to start by mid-2025 with full expansion expected to be operational by 2026.

US infrastructure

A “sister” site is being built by Fujifilm Diosynth Biotechnologies in North Carolina, Petersen said. In April 2024, the company announced an investment of $1.2 billion in its large-scale cell culture CDMO business to further expand the planned end-to-end biomanufacturing site in Holly Springs, bringing the total investment in the facility to more than $3.2 billion. In 2025, operations will begin for the first phase of the facility in Holly Springs.

“This year is very much the year of operationalizing everything we’ve been planning for so long,” Petersen said. “This is a big deal for us because starting up these facilities is very complicated and very expensive.”

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The planned large-scale Holly Springs cell culture facility will add eight 20,000L mammalian cell culture bioreactors by 2028 to the previously planned eight 20,000L bioreactors for bulk drug substance under the initial investment. The goal is to create the largest cell culture biopharma CDMO facility in North America.

With four sites in the U.S., including the expansion of its cell therapy manufacturing facility in Thousand Oaks, California with two new independent production suites that increase cleanroom capacity, Petersen contends that Fujifilm Diosynth Biotechnologies is well positioned to meet the needs of clients. The cGMP suites in Thousand Oaks include automated cell separation, selection, and expansion equipment, as well as in-built decontamination for quick changeovers and HVAC systems that support Grade B or C backgrounds.

UK and Japan

The CDMO’s development plans have also included the United Kingdom. In August 2024, Fujifilm Diosynth Biotechnologies announced the opening of its microbial fermentation manufacturing facility in Billingham, U.K. The site expansion tripled microbial production throughput with the addition of a new line equipped with two 4000L fermenters, a primary separations suite and a modular purification suite.

“In 2026, we will add more facilities — one on a smaller scale in the U.K. — and then the network becomes multiple scales especially in the [monoclonal antibodies] field,” Petersen said. By far the biggest investment the company is making is in the mAbs space “which continues to grow,” he added.

Fujifilm Corporation announced in October 2022 that it is building the company’s first Japanese bio-CDMO

facility in Toyama City. Fujifilm Toyama Chemical invested in the new site, which will be operational in fiscal year 2026 and will include dual-use facilities capable of manufacturing antibody drugs and antibody-drug conjugates and switching to to the manufacture of mRNA vaccines and genetic-engineered protein vaccines.

Petersen said when the Toyama site comes online, it will become part of Fujifilm Diosynth Biotechnologies’ network of service offerings.

Recipharm: From product manufacturer to solution provider

The CDMO has made targeted investments in Europe, India and U.S. With 17 facilities in 10 countries around the world, Recipharm has a global presence with local expertise that rivals some of the biggest contract development and manufacturing organizations, according to CEO Greg Behar, who took the company’s reins in January 2024.

Founded in 1995 and headquartered in Stockholm, Sweden, Behar claims the company —which became private in 2021 and has more than 5,000 employees worldwide — is “one of the oldest CDMOs out there” and is the fifth largest CDMO globally serving the biopharma industry.

Recipharm’s services include the manufacturing of solids, semi-solids, and liquids, supporting the small and large molecule sterile fill-finish needs of its customers, as well as advanced therapy medicinal products (ATMPs) fill-finish and biologics development and manufacturing.

“We have done quite well in 2024 partnering in oral solids, sterile fill-finish and with our bio business,” Behar told Pharma Manufacturing. “We are partnering with eight out of the top 10 pharma,” he said, noting that Recipharm’s revenue last year — nearly $1 billion — grew in the high single digits and the company signed more than 100 biologics contracts.

“This was quite a strong performance given the markets in 2024,” Behar said. In 2025, he projects that Recipharm will exceed last year’s results by achieving double-digit growth.

For nearly three decades, Recipharm has grown organically and through the acquisition of more than 30 facilities. However, Behar contends that since he took Recipharm’s helm last year, the CDMO has “sharpened” its global network and divested some of its non-core sites to become a “more agile” company.

Global presence, local expertise

Currently, Recipharm operates development and manufacturing facilities in France, Germany, India, Israel, Italy, Portugal, Spain, Sweden, the UK and the United States. According to Behar, Recipharm’s full-range of development and production

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We have evolved our relationships with customers from product manufacturer to solution provider.”

— Greg Behar, CEO of Recipharm

capabilities for oral solid dosage (OSD) — from orphan drugs to blockbusters — have been significantly enhanced to meet the industry’s growing demands.

When it comes to OSD, Behar contends that the company has a large footprint and is the “leader” in Europe, including sites in Germany, Italy, Portugal, Spain, and Sweden. Targeted investments in 2024 included the expansion of small molecule development capabilities at Recipharm’s center of excellence in Bengaluru, India, with a new sterile product lab.

The company also invested in three new GMP Pilot Scale suites for blending, tableting and hard capsule filling at its Oral Solid Development and Pilot Scale Center in Zwickau, Germany. The investments at Bengaluru and Zwickau include advanced material characterization equipment, a compression and compaction simulator, a Mini-Pactor for dry granulation, as well as pilot-scale capsule filler and a small-scale tablet press.

“Investment for us is focused more on development because this is where we think that we have an opportunity to increase earlier stage assets, basically compounds — large and small — that are in Phase 1, 2, and 3,” Behar said.

In January 2025, Recipharm’s biologics division ReciBioPharm — which has sites in Germany, Portugal, and the U.S. to work with customers to develop and commercialize ATMPs — was awarded a three-year grant from the Bill & Melinda Gates Foundation to support the global deployment of RNA continuous manufacturing technologies to low- and middle-income countries.

“Being able to bring continuous manufacturing to these countries for the next crisis, when it comes, is super important,” Behar said. “We’re not yet running any drug construct. We’re still in the piloting phase and we’ll choose the drug in 2025, but it should be probably a vaccine.”

The grant will enable worldwide implementation of an RNA continuous manufacturing platform and focus on the advancement of Process Analytical Technologies (PAT) — developed through an $82 million Massachusetts Institute of Technology (MIT) project funded by the FDA — as well as predictive analytics software.

ReciBioPharm contends that its platform will improve the scalability, quality, and accessibility of RNA-based medicines, while helping to advance the company’s goal of developing fully integrated, continuous processes across the biomanufacturing industry.

From manufacturer to solution provider

With the goal of creating flexible, breakable extended-release tablets for global markets, Recipharm and Quebec-based Spektus Pharma announced in January 2025 that they will jointly develop and supply a portfolio of novel central nervous system-focused products using Spektus’ proprietary Flexitab oral drug delivery platform.

Designed specifically for titration-sensitive medications, Flexitab is an oral drug delivery technology that generates patent-protected extended-release tablets March 2025 / PharmaManufacturing.com

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that can be broken into dose-proportional segments, with controlled drug release in both intact and broken forms. Recipharm and Spektus will initially target the growing antidepressant market, which they contend remains a significant unmet need.

“We have evolved our relationships with customers from product manufacturer to solution provider,” Behar said. “We’ve expanded what we do from pure API development with flow chemistry, for example, from Phase 2 onwards, offering also analytical services and product development with our full manufacturing capabilities.”

When it comes to manufacturing, Recipharm in February 2025 announced that its new modular sterile filling system, installed in Wasserburg, Germany, is fully operational and has successfully completed its first production run for a “leading” biotechnology company.

Recipharm’s system performs aseptic filling within a Grade A isolator and operates in full compliance with GMP standards, according to the company, which claims that — unlike traditional large-scale systems — its unit is optimized for small-batch production providing a fast and flexible solution for clinical development projects.

Last year, Recipharm announced an exclusive strategic alliance with Exela Pharma Sciences to bolster its sterile manufacturing capabilities in the U.S. with access to Exela’s facility in Lenoir, North Carolina. Behar said the partnership with the CDMO expands Recipharm’s production of sterile products, including antibody-drug conjugates (ADCs), biologics, and GLP-1s.

“The GLP-1 tsunami continues — it’s not over and we’re very active there,” Behar said. “We are starting to build a footprint with ADCs because we believe that there is a lot coming and we want to be ready.” 

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Deborah Smook

VP Marketing & Business Development, TurboFil Packaging Machines

Automating liquid-filled vial nasal delivery

Best practices for designing automated machinery solutions for bringing these nasal devices to market

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automation & control

With liquid-filled vial nasal delivery devices gaining momentum and market share as an efficient, user-centric drug delivery platform, an inevitable obstacle is automating processes historically performed either partially or completely manually.

The concept-to-completion process of bringing viable nasal devices to market has several potential pain points.

One hurdle is ensuring that detailed vial inspection and final device assembly can keep pace with upstream fill-finishing processes, causing a challenging bottleneck. Additionally, vial fill-finish operations in these settings bring their own inherent issues, most notably dosing precision and repeatability for what is often a miniscule amount of drug product.

With such a diverse range of complex steps, preventing production line bottlenecks and ensuring through-process quality become keys to automation and the increased output it allows. This article discusses step-by-step best practices for automating nasal devices whose primary packaging consists of liquid-filled vials — an increasingly attractive delivery system where solutions for high-volume automation are sought-after, with prominent examples including (but not limited to) the dramatic surge in production for the opioid overdose-reversing drug naloxone.

Nasal device automation, step by step

Until very recently, instances where the up-levelled technology needs of liquid-filled vial nasal delivery devices were squared with attendant equipment engineering expertise were few and far between. However, utilizing such features as racetrack formats and multiple lane construction, it has become more feasible to develop comprehensive automatic filling and assembly solutions that meet these devices’ rigorous manufacturing requirements, while dramatically increasing the number of nasal devices produced per minute. Crucially, these machines also can be designed to fit in a footprint whose compactness reflects the premium placed on cleanroom floor space.

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Considering the delicate handling and intricate maneuvers these machines must perform, this marriage of precision and proliferation represents a quantum leap forward — and opens new and necessary avenues for this platform’s market share growth and overall expansion.

It cannot be understated how truly painstaking the liquid-filled vial nasal device production process can be. To understand that, it’s useful to revert to the research and development (R&D) stages, where such delivery systems are produced using successive semi-automatic benchtop-assisted steps, from filling and inspecting to assembling and final packaging. This arduous, multistep approach generally yields no more than a handful of finished products per minute. Such a setup is workable for R&D stages, but completely unviable — economically or otherwise — for commercialization purposes.

To fully showcase the need for automation, it’s important to start at the beginning of the process. Right from the inspection of yet-to-be-filled vials, it’s clear that automation is not only a preferred production method in this format but, given the volume needed for commercial viability and supply continuity, is entirely necessary to forge a reasonably workable process. A station-to-station review, through the steps performed by today’s next-generation automatic liquid-filled vial nasal device assembly equipment, is critical to understanding the value of automation.

While machines for this purpose can exhibit a variety of different features, for the sake of streamlining our discussion let’s home in on a setup that is becoming increasingly sought-after: an inline, synchronous motor-enabled racetrack system, whose attributes include integrated 360-degree high-resolution camera inspection, valve-less ceramic piston fillers, state-of-the-art assembly functions and — to suit regulatory requirements and promote continuous production improvements — sufficient data collection capabilities.

The bottom line Is that nasal devices are not only here to stay but are bound to become more commonplace.

— Deborah Smook

These are the building block components that, when combined and aligned, can produce the type of exactingly filled and meticulously metering nasal devices required in healthcare settings.

The first stage involves the inspection of unfilled vials. After an air jet and vacuum system cleans all vials, the system’s initial inspection station checks for cracks or other physical defects in each container. To perform this step, vials are raised and rotated allowing 360-degree, high-resolution cameras to leave no section uninspected. The machine also can be equipped with a variety of additional downstream inspection capabilities, including safeguards checking for unstoppered vials, an enhanced lens for exacting fill height verification, and a push-pull station that tests the nasal device’s integrity.

With cosmetic inspection compete, vials are filled via a series of precision valveless ceramic piston fillers, whose volume can be set and calibrated electronically

at an independent, portable cart complete with its own HumanMachine Interface (HMI) setup; the cart is then reconnected to the larger automatic machinery platform.

While the primary inspection for fill volume is performed by cameras at a subsequent station, at this stage an intermittent checkweigher can be employed that diverts a handful of vials at a time, recording their weight for an added layer of upstream quality control and verification. Stoppers are then inserted using a servo-controlled pick-and-place module featuring a burping tube to allow air escape during placement. Notably, the depth of placement in this step must be particularly precise.

The next stage is what can be referred to as primary inspection. The machine lifts the now-filled vials, rotating them 360 degrees, while checking for product fill height, stopper height, and any piston placement anomalies such as liquid droplets between fins — as well as foreign body particulates in the drug itself.

Next, vials are carefully placed into the vial holders and tamped and placed at a predetermined force that is verified via sensor.

Next, one final visual check of the vial rim is conducted prior to actuator placement. These nasal actuators are introduced in-line via a vibratory feeder, and inspected to ensure cannulae are both present and straight.

The nasal devices are automatically placed around the vials, pressed into place with an automatic tamping system which, like the initial vial holder placement, is verified via force gauge.

The next inspection stage is physical: a process that gently tugs on the vial holder to confirm it is firmly affixed to the actuator and exhibits qualities robust enough to perform its intended use properties.

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Automation

Liquid-filled vial nasal device assembly equipment

The completed device is now ready for labeling and is automatically transitioned to a dedicated labeling station with requisite serialization capabilities. Each label also is inspected for print legibility, then again post-adherence to ensure no labelless products enter the marketplace.

Clearly, all this encompasses an abundance of moving parts that must move in perfect synchronization. It’s also important to understand the level of dosing precision required. Since nasal devices nearly always deal in exceedingly small doses, automated device fill and assembly must exhibit keen microdosing prowess capable of meeting or exceeding minute accuracy tolerances — for instance, +/-2.5 microliters on a fill volume of 100-125 microliters.

Likewise, the overall device landscape is similarly infinitesimal; for example, stopper positions generally must be determined down to about 0.3 millimeters to ensure device specifications are fully met. And naturally, cleanliness also is paramount. To bolster sterility, the machine’s product contact parts should be composed of hygienically appropriate materials such as ceramic, 316L stainless steel and Teflon.

Finally, user-friendliness is a necessity in an environment where skilled labor continues to be in short supply. Ideally, an automatic liquid-filled vial nasal device machine will include a large, ergonomic HMI featuring intuitive touchscreen displays for key operator functions like seamless recipe control. Flexibility also is key, meaning an HMI should offer the ability to turn on or off any station or inspection per a particular application’s individual requirements.

March 2025 / PharmaManufacturing.com

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To comply with current regulations, such electronics also should provide individual login functions (i.e. electronic signature), audit trails, record retention, and other safeguards that ensure documentation and accountability.

In addition, such setups also can be outfitted with metrics monitoring that help document mission-critical steps, predict maintenance needs and improve overall production practices.

Remote access functionality is another popular preference, allowing for original equipment manufacturers to conduct necessary maintenance and unforeseen fixes expediently and accurately. Sophisticated manufacturing machinery requires equally sophisticated personnel training, as well as ongoing collaboration with equipment suppliers. To that end, suppliers that will take the long view by parlaying salesmanship into partnership can help drug manufacturers develop solutions that are truly customized and optimized.

Such customization and optimization will undoubtedly be increasingly in demand, for one simple reason: nasal delivery is highly attractive. Compared with syringes, autopens and other injectables, nasal devices deliver drugs less painfully and more expediently.

This latter benefit, speed of drug effectiveness, can be mission-critical in emergency situations, such as those in which naloxone or other life-saving medicines are administered.

The bottom line is that nasal devices are not only here to stay but are bound to become more commonplace. To address the needs of these precision-dependent delivery platforms, manufacturers and machinery experts must continue to collaborate, innovate, and demonstrate the value of these manufacturing automation technologies. 

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Sandy Ottensmann

VP/GM Gene Writing & Editing, Integrated DNA Technologies

Revolutionizing early-stage drug development with rapid genes Faster turnaround times on gene assembly and verification are allowing researchers to focus on their core research activities Advancements in synthetic biology are transforming drug development, with rapid gene synthesis emerging as a game changer. Tools like rapid genes, which offer full clonal genes produced and verified through next-generation sequencing (NGS) in as little as five business days, eliminate tedious cloning for the end user and are helping to propel early-stage drug discovery into a new era.

These innovations significantly reduce time spent on gene assembly and verification, addressing one of the largest bottlenecks in pharmaceutical and biotechnological research: the slow and laborious process of producing constructs. The ripple effects of these improvements are felt across key areas of drug discovery, including therapeutic target identification, biomarker discovery and validation, and drug design.

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MICHAEL ANNINO + SHUTTERSTOCK-AI

drug development

March 2025 / PharmaManufacturing.com

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Accelerating drug discovery, development pipeline

The primary benefit of rapid gene synthesis is the reduction in turnaround time for obtaining high-quality, sequence-verified genes. Traditional gene synthesis products can take as much as 10 days to 15 days to ship, and the delay in gene assembly and verification can hinder progress in preclinical development. Rapid gene synthesis, on the other hand, can reduce this timeline to as few as five business days. This faster turnaround time allows researchers to focus more on their core research activities, shortening the overall duration of the drug discovery and early development process.

Gene synthesis with NGS-verification ensures that genetic material is accurate and ready for immediate use, minimizing the risk of experimental errors due to incorrect sequences.

High-throughput screening experiments, which typically test multiple gene variations, benefit greatly from this accuracy. By eliminating the need for time‑consuming colony screening, researchers can iterate their designs faster, accelerating the pace of innovation.

Shortening the designbuild-test cycle

Synthetic biology is playing an increasingly pivotal role in drug discovery and development by enabling the design and engineering of biological systems to create new therapeutics. One of the most critical steps in synthetic biology workflows is the “build” phase of the design-build-test cycle, where generic constructs are synthesized and assembled for testing. Rapid genes could help overhaul this stage by significantly reducing the time it takes to obtain accurate, high-quality genetic material. In the pharmaceutical,

Drug Development:

Revolutionizing early-stage drug development with rapid genes Synbio Facility, Integrated DNA Technologies

biopharma, and biotech industries, where time is of the essence, speeding up the build stage could prove crucial for accelerating research and development.

Traditionally, synthesizing genes and assembling them into functional constructs would typically take longer than a week, even several weeks for highly complex constructs. This delay lengthens experimental cycles and slows scientists’ progress.

However, rapid gene synthesis can cut this time down by half or more, greatly accelerating research and the design-build-test cycle by allowing researchers to move quickly from the design phase to the testing phase.

As soon as a gene is synthesized, verified, and delivered to the end user, it can be incorporated into functional studies. This allows researchers to immediately assess its performance and determine its characteristics in experiments, such as those involved in therapeutic target identification, biomarker discovery, and drug design.

Faster therapeutic target identification

Identifying the right therapeutic target is one of the first and most critical steps in drug discovery. Synthetic biology tools, including rapid gene synthesis, are enabling faster hypothesis testing and validation. The ability to quickly synthesize various gene sequences can allow researchers to evaluate a broader range of targets simultaneously.

For example, in cancer research, identifying the specific genetic mutations that drive tumor growth is essential for developing precision therapies. Rapid gene synthesis enables faster modeling of these mutations and more efficient validation of potential targets in a preclinical laboratory setting.

Enhancing biomarker discovery, validation

Biomarkers are integral to early drug development, guiding the discovery of new therapies by providing measurable indicators of disease presence, disease

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drug development

progression, or response to treatment. The fast turnaround time of rapid gene synthesis allows researchers to generate and test multiple genetic constructs, thus expediting the identification of biomarkers. This rapid generation of genetic material, paired with NGS verification, could enhance the value of these biomarkers and help increase researchers’ confidence in their experimental outcomes.

For example, researchers investigating biomarkers for neurodegenerative diseases often need to test gene variations associated with specific mutations. With rapid gene synthesis, these sequences can be generated and verified in days rather than weeks, enabling more efficient validation of biomarkers that could later inform clinical trial design.

Optimizing drug design, protein engineering

Rapid gene synthesis can also play a crucial role in helping to optimize drug design, particularly by allowing researchers to efficiently test and refine multiple versions of potential therapeutic candidates. Drug design is often an iterative process where researchers need to create and evaluate various gene constructs to identify the most effective molecular targets.

With rapid genes, researchers can swiftly generate and obtain different gene sequences, enabling them to explore multiple variations of a therapeutic target or drug’s active site simultaneously. This rapid iteration helps reduce the time spent in each design-build-test cycle, which is crucial for drug design optimization.

This can be particularly evident when optimizing the design of biologic drugs, whether that is through the modification of existing proteins or the creation of new proteins that can function as effective therapeutic agents. Rapid gene synthesis plays a crucial role in this protein engineering process, enabling researchers to rapidly test multiple variants of a protein. Different gene constructs can be designed to encode for protein variants with specific modifications, such as altered binding sites, improved biochemical stability, or enhanced catalytic (enzymatic) activity.

With rapid genes, researchers can swiftly generate and obtain different gene sequences.

— Sandy Ottensmann

With rapid genes, these constructs can be synthesized and delivered within a week, allowing for fast testing of their function in experimental model systems.

This quick iteration cycle should help accelerate and optimize the discovery and development of therapeutic proteins, such as monoclonal and next-generation antibodies, enzymes, and receptor ligands, all of which play critical roles in modern drug development.

Expediting directed evolution, high-throughput screening

A common technique used in protein engineering is directed evolution, a process where researchers create a library of protein variants and screen them for desired traits. Rapid gene synthesis accelerates this process by enabling the fast generation March 2025 / PharmaManufacturing.com

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of large libraries of gene variants, which can then be expressed and tested for their functional properties. The faster the gene variants can be synthesized, the more quickly researchers can identify promising candidates that meet specific criteria, such as improved binding to a drug target, enhanced agonist activity, or better resistance to enzymatic degradation.

High-throughput screening of these protein variants can be made even more efficient when paired with rapid gene synthesis. By generating genes in plate formats, such as 96- or 384-well plates, rapid gene synthesis allows for simultaneous testing of dozens or even hundreds of protein variants using automation. This capability is particularly useful in early-stage drug discovery, where finding the best protein variant can mean the difference between an effective treatment and one with suboptimal therapeutic properties.

Streamlining collaboration and innovation

Another factor that can make or break the success of a therapeutic discovery and development project is team collaboration. In biotechnology and pharmaceutical companies, drug discovery often involves multiple teams working on different aspects of the project, from target validation to preclinical testing. Rapid gene synthesis could reduce the friction caused by long wait times for critical materials, enabling different teams to work in parallel rather than sequentially. This streamlining of the process can accelerate overall project timelines, leading to faster decision-making and ultimately, reducing the time to market for new therapies.

The availability of NGS-verified, high-quality genes may also lower

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the barriers to innovation. With gene sequences delivered faster and with greater accuracy, researchers are more likely to pursue exploratory research that they might have otherwise put off due to time constraints. Similarly, a transparent pricing system with no hidden fees allows them to budget accurately, assess, and decide on the feasibility and scope of their experimental projects up front. This freedom to experiment can lead to the discovery of novel therapeutic approaches or potential precision therapies.

Choosing the right vector

An essential aspect of synthetic biology workflows is choosing the right vector, as it directly impacts the efficiency and success of gene expression. Vectors are used to deliver genetic material into host cells, and their selection depends on specific experimental goals and the biological system being used.

The choice of vector relies on having access to a wide variety of bacterial and mammalian expression vectors.

Different research projects demand unique vector systems, depending on whether researchers are working with bacterial strains or mammalian cell lines. The availability of diverse vector options enables scientists to quickly choose the best platform for expressing their genes of interest, significantly speeding up research. For instance, bacterial vectors like pET-based systems can allow researchers to efficiently express proteins in bacterial cells, while mammalian vectors are essential for producing functional proteins in human-like systems.

In addition to pre-configured vectors, the ability to purchase genes in an end user’s own custom vectors is a critical capability for researchers working in complex, niche areas of drug discovery. Many biotech laboratories develop proprietary vectors that are

optimized for their specific research models. Integrating the synthesized genes into these vectors usually requires significant in-house effort, often involving tedious subcloning and troubleshooting.

However, once a custom vector is onboarded with a vendor, the vendor takes over the cloning, integrating it into their standardized gene synthesis workflow. Researchers can then order fully cloned genes in their vector at any time. This offers tremendous time savings, as teams no longer need to re-clone genes for each experiment.

Eliminating the need for in-house cloning allows teams to go directly into functional studies.

The undeniable utility of obtaining genes in proprietary vectors has been recognized as it is now possible to customize these as standard, using new custom vector onboarding tools that facilitate the easy and confidential submission of custom vector sequences online, in a simple process without the need for elaborate communication and direction.

Custom vector onboarding helps ensure that researchers can continue using their established systems without disruption, while still benefiting from advances in gene synthesis technologies.

Having access to a wide array of vectors, as well as the ability to onboard custom vectors, allows researchers to tailor the gene delivery system to their specific needs, ensuring more accurate, efficient, and scalable results in both early-stage research and drug development.

Removing endotoxins from vector preparations

For many applications in drug discovery, particularly those involving therapeutic proteins or gene therapies intended for human cells, the presence

of endotoxins in DNA preparations can be highly problematic. Endotoxins, which are lipopolysaccharides found in the outer membrane of Gram-negative bacteria, can trigger strong immune responses in mammalian cells. If not properly removed, even small amounts of endotoxins can compromise experimental results by causing unwanted immune activation or cell death through apoptosis.

Endotoxin-free DNA preps are therefore crucial for researchers working on projects where DNA needs to be introduced into sensitive mammalian cells. Removing endotoxins during plasmid purification ensures that experiments can proceed without the risk of introducing inflammatory responses, leading to more reliable outcomes. Moreover, for those developing gene therapies or biologics for clinical applications, endotoxin-free vectors are a non-negotiable requirement, as they help ensure the safety and efficacy of the final product. This capability further underscores the importance of high-quality synthetic biology tools in advancing cutting-edge medical research.

The introduction of fast gene synthesis and its ability to accelerate drug discovery marks an important moment in biopharmaceutical research. By drastically reducing the time needed for gene synthesis and verification, these tools enable faster progress in key areas such as therapeutic target identification and biomarker discovery.

Further, their potential role in facilitating teams to drive innovation quickly opens the door to more personalized and precision therapies that require a rapid pace of development.

The impact of rapid gene synthesis on pharma will only become more pronounced, promising faster drug development and more effective treatments for patients worldwide. 

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MICHAEL ANNINO + SHUTTERSTOCK-AI

supply chain

Bioprocessing by SEKISUI Paul Bennett

Principal Scientist R&D

Kirsty Bellchambers

Study Leader R&D

Overcoming enzyme manufacturing challenges Therapeutic enzymes are increasingly important in drug development, but scaling them presents various challenges

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Enzymes are in growing demand as drug substances for antimicrobials, anticoagulants, and enzyme replacement therapies for a range of disease areas. Enzyme manufacturing processes come with a unique set of challenges — for example, unlike antibody manufacturing, it is more challenging to develop a platform production process that can be applied to many different enzymes. Because every enzyme is unique, it is often necessary to establish a unique, tailored process for each.

Enzyme production must be designed to balance high yields with high purity from an economically viable process. Developers might not recognize that processes that

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work in-house or in a small-scale lab environment can be difficult to transfer to a contract manufacturer, and some just aren’t feasible for scaled-up manufacturing.

Many companies also don’t perform an in-depth build versus buy analysis during development. As a result, in the early days it can seem to make sense to carry out as much as possible in-house. Eventually, if their business model is successful, companies can wind up victims of their own success. They may reach a point at which outsourcing is preferable for quality and outscaling reasons — but by that point, demand catalyzes pressure on their end and timetables need to be short to advance to larger-scale production.

It is easy to underestimate the time it can take to successfully develop or transfer processes to a production environment. While timelines can be somewhat streamlined by working with an experienced contract development and manufacturing organization (CDMO), given the challenges a developer may face along the way to scalable enzyme manufacturing, it is still crucial to gain an in-depth understanding of each process step and the obstacles they may still need to overcome.

must align to the latest guidance from local regulators. In Europe, for example, materials used should be compliant with Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulations to progress to product manufacture. Sourcing particular GMP-grade materials can be a challenge, and sufficient time needs to be included in the project timeline to achieve this and qualify them into the CDMO’s QMS. Typically, process development starts with consideration for the recombinant protein, the clone itself, and the cell banks. In some cases, a developer already has all of these in hand, but in others some pieces are missing which might mean a construct needs better expression, or a master cell bank must be created.

Characterization of the cell bank is important to ensure that cells maintain their genetic and phenotypic properties. When working with Escherichia coli (E. coli), a common enzyme expression system, it is critical that cell banks are bacteriophage-free, as the presence of phages could have a serious impact on manufacturing operations.

For clinical trials, GMP-grade materials have their own defined standards but — despite a high level of quality assurance — the GMP cell bank might not provide the level of expression anticipated.

Every enzyme has its own unique set of properties that need to be understood, adding layers of complexity to any manufacturing process. It’s here that experience is useful to manipulate conditions to achieve a combination of high expression, yielding good quality and active protein.

Enzyme manufacturing challenges

There are multiple challenging aspects of enzyme manufacturing related to fermentation. In E. coli, high cell density is achieved by careful manipulation of temperature, pH, growth and induction conditions. Managing the right balance of substrates and minimizing the formation of growth-inhibitory metabolic waste products can also ensure

Scaling down: A good pilot facility includes scaled-down tools that are representative of commercial-scale equipment.

Quality from the start

An experienced CDMO will want to determine what quality is required for a new project from the start. It is crucial they have an advanced quality management system (QMS) to ensure that the right foundations are in place from the very beginning, including the utilization of fully qualified raw materials from trusted suppliers.

Regardless of the desired output, it will be necessary to build in quality materials from R&D that are transferable to operations. Material selection

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supply chain

the culture is in a healthy state to maximize cellular productivity. Oxygen is a critical substrate to consider, as the ability to sustain the high oxygen demands achievable at small scale might be a bottleneck for a large-scale fermentation process.

To increase yield, some developers can also push the fermentation envelope too far. Getting the right balance is important. If the fermentation is not harvested at the right time, the recombinant enzyme can start to degrade. Companies may not have gathered sufficient data to understand the most productive point to harvest the fermentation, where cellular productivity is highest.

Fermenter occupancy time also comes at a premium and energy and material costs need to be considered, hence shortening fermentation run times can help to reduce manufacturing costs and complexity.

Every enzyme has its own unique set of properties that need to be understood, adding layers of complexity to any manufacturing process.

Additionally, although the technology associated with on-line monitoring is rapidly advancing, some monitoring is still performed by operators, like taking samples to measure enzyme activity.

If cellular expression during the fermentation process outstrips the rate of protein folding, it can cause the formation of aggregated protein into inclusion bodies.

The ability to solubilize and re-fold from such structures is a significant challenge for the manufacture of many enzymes. In these cases, the ability to achieve active, soluble expression during the fermentation process typically becomes the main goal.

The complicated structure of some enzymes may also call for very targeted expression approaches. For example, if the enzyme has disulfide bonds, it might require a signal peptide to direct expression to the E. coli periplasmic space to achieve correct folding.

During fermentation, there can also be issues where the recombinant protein is toxic to the host cells. For instance, DNA modification enzymes can trigger an irreversible stress response in cells, leading to significant morphological changes. Selective induction methods and fermentation strategies to decouple cellular growth from recombinant protein expression can be adopted, although even low levels of unintended or “leaky” expression can still sometimes cause issues. Toxicity may be circumvented by producing inactive pro-proteins in cells for activation in a subsequent step.

Another consideration is the use of antibiotics, which are employed during fermentation for several purposes. One of them is appropriate selection of the right clone, as the plasmid containing the recombinant gene will be designed with an antibiotic resistance marker. This also helps with retention of the plasmid during the seed stages and, often, final fermentation production stage. Selection of the right antibiotic needs to be considered from the start. In particular, beta lactam antibiotics require very strict control given their hypersensitivity and are best avoided in a GMP setting. It is also necessary to demonstrate antibiotic clearance from the final product to ensure quality and safety.

March 2025 / PharmaManufacturing.com

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Process development challenges

Complications during tech transfer are not uncommon. Everything hinges around the target specifications, such as host cell DNA or protein, but developers’ analytics may not be robust enough. Developers often have limited data as a result, which might mean they have identified a problem but don’t fully understand it. Purity is a common example, where some seek to use a SDS-PAGE technique to estimate, but that does not reveal enough detail.

In this case, mass spectrometry might be needed to understand different product forms. Further, all analytical methods have matrix effects, so every different condition that an enzyme is in can influence the result.

A CDMO may also be at the whims of its external service providers in some instances, such as handling specialist test requirements, and so this needs to be understood and suitably built into the timeline.

Chromatography steps are utilized to achieve the high levels of purity required, and there are many factors to consider. These include the amount of protein loaded onto a chromatography column, as well as binding and elution conditions to separate contaminants from product. There is a temptation to maximize for full recovery but the result can include a poorly understood contaminant that then needs to be characterized. Ultimately, some developers try to achieve everything in one chromatography column, which can be difficult and lead to a non-robust process with repeat product failures.

Processes that improve purity can be complex and each additional step in such a process is an opportunity to lose product. It is a necessary challenge to simplify as much as possible

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to maximize yield, while still being able to achieve high purity targets. Affinity tags can be a useful way to purify enzymes but that approach is not always straightforward and can still lead to purification issues. Further, the tag can potentially impact the end-use performance of the product unless removed, and so the construct may need to be engineered to introduce a suitable cleavage site to remove it.

Scaling up

Scale-up goes most smoothly when starting from a good pilot facility, with scaled down tools that are representative of commercial-scale equipment. That includes fermenters, chromatography systems, tangential flow systems and centrifuges, so the developer and manufacturer can truly understand all relevant parameters throughout the entire process. This is not always possible as certain centrifuges are a particular challenge.

Large-scale disc stack centrifuges for continuous separation can be difficult to model. Even how you harvest cells can impact the effectiveness of a purification strategy. For instance, cells are recovered as a slurry from disc stack centrifuges and if cell wash steps are introduced, that can lead to unwanted lysis. Typically, cell paste produced by the expression system is frozen down to -80°C, and so storage capacity needs to be considered.

With E. coli as the host, the recombinant enzyme is typically expressed intracellularly and following lysis developers need to consider the vast amount of debris that would need to be cleared at a large scale, as well as the extent of nucleic acid and other contaminants that are released.

Charged flocculants can help facilitate clearance of such material. This can reduce the high costs associated with using membrane filtration to achieve

the clarity needed before proceeding with more sophisticated purification techniques.

As developers look to scale up, they can sometimes forget about how much chromatography resin they will need for the manufacturing process.

As a result, they end up with very large columns and must incorporate cycling. This means holding material so that you can process part of it in one chromatography step, clean that, and start again. A developer can end up needing multiple cycles to purify an entire batch. This adds additional time constraints that can lead to stability issues.

Grappling with degradation

Some proteins are more susceptible to degradation than others. If protein degradation is apparent during expression, the use of protease knockout strains can help reduce or prevent degradation of the recombinant protein during the fermentation. Lysis and chromatography conditions, such as pH, buffer selection and temperature control, can also be manipulated to minimize degradation. However, there may be limitations imposed by the stability of the protein. For example, particular pH conditions might influence solubility. Certain additives can also be included to help stabilize the enzyme, such as protease inhibitors, reducing agents and metal ions. But using them can have consequences as the presence of metal ions, for example, can affect chromatography steps.

As a process moves toward largescale manufacturing, there are other threats to stability. If conditions are not optimal, some enzymes can begin to degrade right away. Developers sometimes overestimate how much active enzyme they can get from cells, leading to an unpleasant surprise that gets compounded if they also didn’t

account for degradation due to the increase in the timing of steps that can occur during scale-up.

Stability of the final enzyme product is a challenge with many different facets. Producing an enzyme with an appropriate shelf life is key, which is highly dependent on formulation. At early stages of development, however, it can be very difficult to predict. Some clients impose additional risks to stability because they are considering processing at ambient temperatures to avoid process complexity and facilitate transfer to a CDMO. Cooling and cold rooms would otherwise be required, and not all CDMOs can offer this capability at large scale.

Elevated temperatures enhance reactions, and if proteases are present, this can be a fundamental problem that requires stepping back into development to really understand whether conditions are sufficiently stable.

Innovation is often perceived in terms of a new technology, platform or piece of equipment. In reality, any advance that improves how a product comes into fruition is valuable and process development offers many opportunities for this.

Enzyme production comes with a large number of variables that must be considered in the design of a manufacturing process, and design of experiments can be helpful to home in on the most critical ones. It is important to carefully think through and design purification strategies that are amenable to large scale.

Understanding an enzyme product’s characteristics and properties can help guide development of the most effective processes. Companies often benefit from guidance from a process development partner with an experienced R&D team with synergistic capabilities and a full understanding of manufacturing constraints. 

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Manufacturing Sector News

MANUFACTURING Delivering the latest trends and expert analysis to professionals responsible for innovation and growth strategies.

Insight and analysis from manufacturing and sector experts into the global manufacturing economy.

Learn More:

markets.endeavorbusinessmedia.com/market-moves-newsletters

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3/15/23 12:33 PM 2/17/25 4:38 PM

engineering angles Rick Flock

PE, Affiliated Engineers Inc.

Assessing cleanroom suitability Understanding the location and existing infrastructure are critical to creating a successful cleanroom

The United States leads in pharma and biopharma manufacturing, with biologics, gene therapies, and vaccines driving the demand for cleanroom construction. A November 2024 Global Market Insights report states U.S. cleanroom construction exceeded $1.2 billion in 2023 and is expected to grow at over 7.1% CAGR from 2024 to 2032, with pharma holding a significant market share.

But finding suitable real estate for a cleanroom installation can be challenging. Besides managing the significant expenses, companies must assess whether the building fulfills the necessary location, structural, and utility requirements to accommodate their operational demands and comply with regulatory standards.

Location, location, location

Though part of a larger facility, nearby activities can impact cleanroom conditions. An ideal site should minimize exposure to particle contamination risks, like high exhaust levels or heavy industry.

Cleanrooms should be placed away from heavy truck traffic, loading docks, and industrial sites to prevent air pollution, vibration, and noise that may release particles. Natural hazards like floods, earthquakes, and wildfires must also be assessed for operational risks. Reliable access to electricity, water, suppliers, and staff is crucial for efficient pharma manufacturing.Lastly, the building in question should comply with local zoning laws and scientific

and industrial use regulations. Any regulations relating to waste disposal, emissions, or water use that may impact operations should be identified before committing to a particular site.

Structural suitability

Cleanrooms need 16 to 20 feet of clear space for HVAC systems, including plenums, HEPA filtration, humidifiers, dehumidifiers, and airhandling equipment. Lower floorto-floor heights can compromise efficiency and function. The structure must also support the cleanroom’s weight, including filtration systems, airflow controls, and heavy vibrationsensitive equipment.

Further, the building must be able to accommodate future growth, cleanroom expansions, or scaling up operations. Ideally, such a space should have easily adaptable attributes that can be reconfigured as technology evolves, upgrades occur, and regulatory requirements change.

HVAC and piping

Cleanrooms are mechanically intense, requiring more HVAC, chilled water, steam, and heating hot water than most facilities. Understanding how workloads fit within the building’s infrastructure is crucial. Low floor heights or lightweight steel may require extra substructures to support HVAC and process piping. The building must have proper outdoor air intake locations, away from facility exhausts and areas with vehicle traffic or idling.

Electrical infrastructure

Cleanrooms consume substantially more energy than non-classified rooms requirng electrical power to accommodate HVAC process equpment and support process systems.

HVAC systems use 50% to 75% of a cleanroom’s electricity due to high airflow. Process applications also require varied voltages (120, 230, 277, 480), so existing power infrastructure must be evaluated.

Many pharma companies adopt green standards like LEED. Facility selection should consider energy-efficient design and renewable energy options.

Obtaining assistance for site evaluations

Consulting an architect and engineer is essential to confirm a property’s suitability for a cleanroom project, including attributes such as: • Adequate space and infrastructure to support cleanroom construction • Absence of environmental hazards and contamination risks • Sufficient power supply of the appropriate type • Compliance with local zoning and regulatory requirements • Flexiblity to accommodate future expansion and technology upgrades Taking the time to assess these factors will ultimately lead to an optimal cleanroom environment that meets current needs and future growth potential. 

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taking stock Adrian Wood

Director of Strategc Business Development at Delmia

Exploring the future of supply chain in 2025 What can pharma companies do to prepare for the year ahead and beyond?

Darwin’s theory suggests adaptation takes millions of years, but business now adapts in minutes.

In 2025, how will supply chains evolve? Pharma companies are already considering impacts and strategies.

Global economic relations

U.S.-China relations will remain key to global supply chains in 2025.

Post-election, trade tensions may escalate, leading to tariffs, restrictions, and possible decoupling.

However, this could create opportunities for alternative hubs like India, Vietnam, Mexico, and Poland.

Trade policies

Global supply chains are also likely to be impacted by “protectionist” measures and new trade agreements such as the EU’s Carbon Border Adjustment Mechanism and national efforts to curb inflation. These efforts tend to form “gated globalization” which will limit the flexibility of supply chains within smaller geographic areas of “friendly” trade partners.

Unfortunately, ongoing global tensions and conflicts also continue to disrupt key regions, making it necessary to diversify trade routes and build more resilient supply chain networks.

Material impacts

Many supply chains are dependent on resources that continue to be critically constrained. For example, increasing demand for lithium and other materials crucial for electric vehicle batteries.

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Industries, such as semiconductors, also rely on rare earth elements as well as increasing cost and effort to build critical manufacturing capacity.

On a positive note, these same challenges are also driving new innovation in material science and recycling technologies, as well as investments in new extraction and processing facilities.

Sustainability pressures

Environmental concerns will keep shaping supply chain strategies due to natural and human impacts.

After major weather disruptions in 2024, companies expect similar challenges this year. Growing consumer and investor pressure for sustainable, low-carbon supply chains may drive new regulations and reporting requirements.

However, these challenges also present opportunities, such as increased investment in green technologies and localized production.

Leveraging technology

Just as the physical and natural world are changing around us, so is technology.

While supply chain planning software is certainly not new, it has evolved quite significantly over the last decade, with the latest evolutions gaining critical capabilities that companies are going to leverage in the near future: • Scientific accuracy: Precision in supply chain planning reduces errors, improves forecasting, optimizes inventory, and minimizes

disruptions, boosting efficiency and competitiveness.

• Enterprise-wide collaboration: Seamless integration across the product lifecycle enhances efficiency, reduces disruptions, and shortens time-to-market. Cross-functional communication helps address issues, optimize resources, and maintain a competitive edge.

• Artificial intelligence: AI and ML are crucial for supply chain planning, processing vast data for real-time insights. They enhance predictive analytics, improving demand forecasting and inventory management for greater resilience and efficiency.

AI is transforming industries and daily life, optimizing supply chains, inventory, and logistics. Advances in computing and real-time data enable companies to react to disruptions and model business scenarios with virtual twins. As personal automation grows, businesses face the same shift — but do they trust AI to handle complex tasks once reliant on human oversight?

Looking ahead

Geopolitical shifts, climate challenges, and resource constraints will pressure supply chains but also drive innovation and resilience. Rapid advancements bring trust and security concerns, especially with AI-driven decisions.

Those embracing technology and adapting to change will thrive, making strong tech partnerships essential for digital transformation. 

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2/16/25 6:34 PM

final dose Greg Slabodkin Editor-in-Chief

Lonza’s 2024 results and what they reveal about 2025 CEO Wolfgang Wienand promises significant growth ahead for the world’s largest CDMO by revenue.

As the world’s largest contract development and manufacturing organization by revenue, Switzerland-based Lonza garners its share of industry attention. That was particularly true in late January when the company reported its full-year 2024 financial results.

Lonza announced sales last year of 6.6 billion Swiss francs, which was virtually flat compared to 2023 at constant exchange rates (CER), impacted by the loss of COVID-related mRNA revenue from the termination of a Moderna contract.

Still, after adjusting for this impact, Morningstar analyst Rachel Elfman noted that underlying sales grew approximately 7% at CER with Lonza’s “narrow-moat” underscored by the “resilience of its CDMO business, which continues to perform well despite the loss of COVID-related sales.”

Lonza reported strong “low-teens” year-over year CER sales growth in its core CDMO business in 2024, while the company’s Capsules & Health Ingredients (CHI) business last year was hit with “market headwinds” causing sales to decline 6.6% on “soft demand” for pharma capsules due to customer destocking.

Will 2025 be better?

Looking ahead, Elfman wrote in a note to investors that Lonza is “well positioned to deliver strong performance, particularly in the fast-growing biologics and cell and gene divisions.”

CEO Wolfgang Wienand in his full-year results presentation said Lonza’s biologics division in 2024 saw underlying low-teens CER sales growth, driven by strong performance in mammalian and bioconjugates with initial signs of recovery in early-stage business.

“On the back of strong demand in its commercial large-scale mammalian and bioconjugates businesses, as well as signs of recovery in its early-stage business, we believe Lonza remains well on track to hit its 2025 CDMO guide, which we estimate incorporates roughly 11%12% organic revenue growth for its key biologics segment,” William Blair analyst Max Smock wrote in a note to investors.

Lonza’s $1.2 billion acquisition in 2024 of the Genentech facility in Vacaville, California, one of the world’s largest biologics manufacturing facilities, could position the CDMO to benefit as large-scale mammalian capacity remains in high demand.

However, Smock said “impressive demand for Vacaville is unlikely to lead to material upside to numbers this year, but in our view it should enable management to at least hit its recently issued targets for lowteens organic CDMO revenue growth beyond 2025.”

This year, Lonza expects CER sales growth of 20%, excluding CHI, while the company expects low-to-mid single-digit CER sales growth for CHI. Despite having industry-leading profit

margins, Wienand maintains that CHI’s product business differs from Lonza’s long-term contracted services, with different manufacturing models, technologies, and “very limited actionable customer overlap.”

One Lonza

Wienand, who became CEO in July 2024, is spearheading the new “One Lonza” strategy announced at the end of last year, with the goal of becoming a “pure-play” CDMO. While the new operating model is being finalized and will be implemented in the second quarter of 2025, what is known is Lonza will be restructured from nine to three units — Integrated Biologics, Advanced Synthesis, and Specialized Modalities — and will divest the CHI business “at the appropriate point in time.”

Though Smock said there are some signs of its continuing recovery, CHI “remains a drag” on Lonza due to “limited synergies” with the company’s other units as it is a “strategic misfit” due its product- rather than service-based business model.

“We are pleased to hear management reiterate its commitment to exit the business at an appropriate time, although it noted that the process is still in its early days,” Smock wrote. “We believe that Lonza’s story will become even more attractive once the CHI overhang is removed and the company becomes a pure-play CDMO operating under its revamped ‘One Lonza’ integrated strategy.” 

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