Topic: General

What’s hot and what’s not in ATMP? Insights from service providers, investors, and academics at the 2024 BIO-Europe conference in Stockholm.

BIO-Europe celebrated its 30th anniversary in Stockholm, Sweden, on November 4–6, 2024, bringing together over 5,000 delegates from around the world.

Post-pandemic, life science companies face funding challenges, emphasizing the need for solid data over visions. The Nordic region, though small individually, thrives through innovation and collaboration, with promising developments in manufacturing and funding strategies. Trends in CGT, such as diversification beyond mRNA and integrating AI for efficiency, are discussed in this article. Challenges in manufacturing and affordability remain critical. Despite hurdles, optimism persists, with Nordic companies leveraging global partnerships to remain a hotspot for CGT innovation.

Read the full conference report by Helena Strigård, Roger Lias and NorthX Biologics’ very own Eva-Karin Gidlund, in Cell & Gene Therapy Insights here.

Based on a blog post by NorthX Biologics’ CEO Janet Hoogstraate at Stockholm Science City Foundation

Sweden holds a unique position in life sciences and has, for decades, been a leading nation in research and innovation. With renowned universities, colleges, and a dynamic startup environment, Sweden has established itself as an innovation engine in the field. But it is not only in research and development where Sweden excels. We also have a long and successful tradition of pharmaceutical manufacturing, both for companies’ own products and through contract manufacturing. This gives us a unique standing as a production hub in the life sciences sector. 

The government’s new life science strategy highlights pharmaceutical production alongside innovation. This is an important acknowledgment of the role high-tech manufacturing plays in Sweden’s competitiveness. The production of pharmaceuticals and advanced therapies, known as ATMP (Advanced Therapy Medicinal Products), contributes not only to export revenues but also strengthens our national preparedness and self-sufficiency. Nowadays, it is no longer necessary to take innovations abroad; in Sweden, we have established innovation environments such as Testa Center, NorthX Innovation Hub, and CCRM Nordic that bridge innovation to industrial production domestically. 

An important part of Sweden’s GDP 

The pharmaceutical industry already plays a significant role in Sweden’s economy. According to the industry association Lif, pharmaceutical exports continue to be a strong driver of the Swedish economy, creating a positive trade surplus. To maximize the value of life sciences in Sweden, it is crucial that the entire value chain is present – from research and development to the production and commercialization of pharmaceuticals, therapies, and medical devices. However, this requires creating conditions for further investments in manufacturing in Sweden. 

A strong production sector can also stimulate other areas of life sciences, such as clinical trials and research. Simultaneously, domestic pharmaceutical production provides Sweden with increased resilience in situations where global supply chains risk being disrupted, as highlighted during the pandemic. 

Securing competence – a key issue 

To maintain and develop Sweden’s competitiveness as a production hub in life sciences, securing skilled labor is essential. The manufacturing industry needs dedicated, meticulous, and knowledgeable employees. But how do we get more people to view life sciences manufacturing as an attractive career path? Tomorrow’s workforce is not only looking for a job but also for opportunities for growth, flexibility, and purpose. 

One step in the right direction would be to establish and further develop educational programs closely linked to the industry’s needs. Examples include apprenticeship or trainee programs where the government and private sector collaborate. Such programs could lower the barrier for newly educated individuals to enter the workforce while ensuring the industry has access to the required skills. A clear and well-structured pathway into the labor market also makes Life Sciences more appealing to students when choosing their education. 

To further strengthen the availability of skilled workers, Sweden should actively work to attract educated professionals from other countries. It should be easy to move to Sweden and stay here, with support for relocation, housing, and language training at the appropriate level. Additionally, resources should be available to support partners and families, contributing to a safe and welcoming environment for international talents. This is crucial for ensuring Sweden can compete for the best global talent. 

A holistic approach that creates value 

With the entire value chain in Life Sciences – from research to high-tech manufacturing – we can continue to create jobs, tax revenues, and increased knowledge. This results in products and services that improve public health and strengthen Sweden’s role as a global leader in life sciences. However, achieving this requires collaboration between the government, educational institutions, and industry to ensure we do not lose our competitive edge. Let us build on Sweden’s strengths and secure a sustainable future as a production country in life sciences.

The pharmaceutical industry is experiencing a rapid transformation as advanced biologics – viral vectors, recombinant proteins, plasmid DNA, and cell and gene therapies – take center stage. With over 14,800 active biologics innovation programs in development, including monoclonal antibodies, viral vaccines, and gene therapy vectors like AAVs and adenoviruses, the demand for specialized biologics contract development and manufacturing organizations (CDMOs) is soaring. Plasmid manufacturing remains integral to these innovations, underpinning gene therapies, DNA vaccines, and mRNA manufacturing.

Manufacturing these advanced therapies is a highly complex process that requires careful control over production platforms and scale-up strategies. For viral vectors, the process begins with a master cell bank (MCB), containing cells such as HEK293 or Vero that have been optimized for viral vector production. The viral seed stock, a small, well-characterized batch of virus, is used to infect the MCB during upstream processing. The viral particles are then expanded in either suspension bioreactors or adherent systems like the iCellis500 platform. This is followed by cell lysis, endonuclease treatment, and depth filtration to remove debris. Tangential flow filtration (TFF) further concentrates the viral product, while chromatography ensures the removal of impurities during purification. The process culminates in formulation and aseptic fill-finish, ensuring the product meets regulatory and safety requirements.

Recombinant protein services and plasmid manufacturing

For recombinant proteins, microbial systems such as E. coli or mammalian cell lines like CHO are commonly used. Microbial production often leverages transient expression, where plasmids containing the gene of interest are introduced into bacterial cells for rapid protein synthesis. In mammalian systems, cell banks provide stable production platforms where cells are expanded, transfected with the target gene, and induced to produce recombinant proteins. After fermentation or cell culture, purification involves ultrafiltration, diafiltration, and chromatography to isolate the desired protein, followed by formulation and fill-finish.

Plasmid DNA, essential for gene therapies and mRNA vaccines, is manufactured using microbial fermentation systems. A carefully selected host strain of E. coli is used to amplify plasmid DNA during fermentation. After cell harvest and lysis, the plasmid is separated from host DNA and proteins through filtration, chromatography, and buffer exchange processes. The purified plasmid DNA is then formulated and filled aseptically under GMP conditions. NorthX Biologics has excelled in this space, offering scalable plasmid DNA production, ensuring a seamless transition from research-grade material to clinical GMP batches.

Biologics CDMO services

NorthX Biologics has emerged as a leader in the advanced biologics space by integrating these complex manufacturing processes into streamlined, end-to-end solutions. Our capabilities span viral vectors, recombinant protein services, plasmid manufacturing, and cell therapy services. In cell therapy manufacturing, we leverage allogeneic or autologous cell banks, expanding cells in controlled GMP cleanrooms. Cells undergo activation, differentiation, and harvest, followed by aseptic filling and cryopreservation to ensure product viability.

These manufacturing capabilities are supported by NorthX Biologics’s expertise in process development, regulatory compliance, and analytical testing. By offering upstream process optimization, purification, and aseptic fill-finish under one roof, NorthX Biologics significantly reduces timelines while ensuring product quality.

The success of NorthX Biologics’s approach is demonstrated in real-world collaborations. During the OPENCORONA project, NorthX Biologics rapidly produced GMP-grade plasmid DNA for a SARS-CoV-2 vaccine, meeting strict quality and regulatory standards. In viral vector manufacturing, NorthX Biologics enabled HOOKIPA Pharma to scale a novel immunotherapy product to 200L using their transient expression processes and robust purification techniques. For Mendus, NorthX Biologics established GMP cell therapy manufacturing capabilities within just eight months, ensuring a smooth tech transfer and rapid scale-up for clinical production. Similarly, in collaboration with Abera Bioscience, NorthX Biologics supports the GMP manufacturing of outer membrane vesicles (OMVs), leveraging microbial processes to produce these naturally occurring particles for innovative vaccines.

Aseptic fill-finish and analytical expertise

To meet growing market demands, NorthX Biologics has invested in two European facilities equipped for microbial and mammalian production. These sites include BSL2 and BSL3 capabilities, supporting a range of biologics platforms. Our aseptic fill-finish services adhere to Annex 1 regulations, providing the highest level of assurance for clinical and commercial products. Additionally, NorthX Biologics’s in-house analytical expertise ensures rigorous quality control, from biologics process development and in-process monitoring to release testing and stability studies.

As advanced therapies continue to evolve, the role of biologics CDMOs in enabling efficient and scalable manufacturing becomes increasingly critical. NorthX Biologics stands out as a true partner in innovation, seamlessly integrating cell banking, seed stock preparation, transient expression systems, and robust purification and analytical technologies to support pharmaceutical innovators. By combining decades of GMP experience with cutting-edge manufacturing capabilities, NorthX Biologics is well-positioned to deliver life-saving therapies faster and more efficiently, helping patients worldwide benefit from the next generation of biologics.

On behalf of the Swedish Ministry for Foreign Affairs and Gavi, the Global Vaccine Alliance, NorthX Biologics’ CEO Janet Hoogstraate participated in an important roundtable on “Leveraging Technology and Innovation to Ensure Every Child is Vaccinated” on December 10, 2024. Joined by other Swedish companies and international organisations with experiences in pioneering innovations in technology and sustainability, together they explored how to contribute to reaching the 14.5 million children in the world who still lack vaccines.

Read Janet’s statement below.

Your excellencies, Ladies and Gentlemen,

It is an honor to join this important conversation about leveraging technology and innovation to ensure every child is vaccinated. At NorthX Biologics, we are deeply committed to driving change and contributing meaningfully to this global effort.

First, scaling up vaccine manufacturing processes is at the heart of what we do. By leveraging cutting-edge technologies and robust expertise, NorthX Biologics is well-positioned to increase production capacity for both new and existing vaccines. This ensures rapid response to global health needs.

Second, we believe in the power of technology transfer to low- and middle-income countries. Establishing local manufacturing hubs is crucial for self-sufficiency and long-term vaccine security. We are ready to collaborate with partners to transfer our expertise and support the creation of regional production capabilities. We are proud of our history of working on scaling up and manufacturing of clinical trial material for a more affordable polio vaccine, having been part of two projects supported by the Bill & Melinda Gates Foundation.

Third, capacity building is essential. At NorthX Biologics, we prioritize training staff in Good Manufacturing Practices (GMP), biotechnology, and advanced analytical techniques. By equipping local teams with the skills they need, we help build sustainable ecosystems for vaccine development and production.

Fourth, we recognize the urgent need for cost-effective solutions. By working to redesign and redevelop vaccines—for instance, making them more stable so they can be transported at room temperature rather than refrigerated—we can make vaccines more accessible and reduce logistical challenges. We are currently a partner in an oral cholera vaccine project collaborating with professor Jan Holmgren and the International Vaccine Institute. These partnerships demonstrate our commitment to advancing vaccine access and global health equity.

Finally, our capabilities extend to manufacturing new vaccines and quality control analyses to ensure their safety, quality and consistency.

NorthX Biologics is not just a manufacturer; we are a partner in innovation, committed to finding creative solutions to global challenges. By collaborating with governments, non-profits, companies and other stakeholders, we can collectively work towards a future where no child is left behind in receiving life-saving vaccines.

I look forward to exploring new approaches and opportunities for collaboration with all of you. Together, we can ensure a healthier, brighter future for every child.

Based on a presentation given by Thomas Eldered at the PharmaOutsourcing event, Stockholm, Sweden, December 2024.

From vertical integration to decentralization

The pharmaceutical industry has undergone a seismic shift over the last several decades, transitioning from a vertically integrated model to a decentralized ecosystem of partnerships and specialized services. This transformation has ushered in what many now recognize as the CDMO era – an age defined by outsourcing, collaboration, and rapid innovation. For investors, this evolution presents a unique opportunity to engage with a sector that is both resilient and dynamic.

Historically, pharmaceutical companies operated under a fully integrated model, where they controlled every aspect of drug discovery, development, and manufacturing. This model dominated for much of the 20th century, providing developers with full control over their intellectual property, supply chains, and manufacturing processes. However, as the complexity of drug development grew, the limitations of this approach became apparent. The cost of maintaining in-house expertise for increasingly specialized tasks, coupled with the inefficiencies inherent in such a broad operational scope, began to erode the model’s viability.

The late 1990s and early 2000s marked a pivotal turning point. Advances in biotechnology during this period brought about the “biotech revolution”, shifting the industry’s focus toward complex biologics, including monoclonal antibodies, cell therapies, and gene therapies. These modalities required specialized knowledge and infrastructure that many pharmaceutical companies lacked. Simultaneously, the competitive pressure to reduce time-to-market and development costs became more pronounced. These factors paved the way for the rise of Contract Development and Manufacturing Organizations (CDMOs).

The 2000s saw the rapid proliferation of CDMOs, with companies like Covance, Charles River, and Recipharm emerging as major players in the field. These organizations offered a compelling value proposition: they provided access to specialized expertise and state-of-the-art facilities, enabling pharmaceutical firms to focus on core competencies like research and commercialization. By outsourcing development and manufacturing tasks, companies could reduce their risk in operating manufacturing facilities running half empty, and thereby reduce their capital expenditures, manage risks more effectively, and accelerate product development timelines.

A new era in pharmaceutical development

This shift toward outsourcing marked the beginning of a new era in pharmaceutical development. The model of the “virtual organization” emerged, where biotech startups and even mid-sized firms operated with minimal in-house teams, relying instead on an extensive network of external partners. This approach proved particularly well-suited for early-stage companies, which often faced resource constraints but needed to navigate complex regulatory and technical challenges.

By 2010, the CDMO sector had become an integral part of the life sciences ecosystem. The global CDMO market was expanding rapidly, driven by several key factors. First, the demand for biologics and personalized medicine continued to grow, requiring specialized manufacturing capabilities. Second, the industry faced increasing regulatory scrutiny, necessitating advanced analytical and compliance expertise. Third, the globalization of pharmaceutical supply chains highlighted the need for flexible and scalable manufacturing solutions.

Today, the CDMO industry is a cornerstone of pharmaceutical innovation. The market is characterized by a high degree of specialization, with firms offering tailored solutions across various modalities, including small molecules, biologics, and advanced therapies. This specialization is complemented by a trend toward consolidation, as larger CDMOs acquire smaller, niche players to enhance their capabilities and geographic reach.

In the late 1990s, Thomas Eldered experienced a pivotal moment during a board meeting at a mid-sized pharmaceutical company. The team, juggling the dual challenges of R&D and manufacturing, faced mounting pressure to deliver a promising biologic. One executive’s comment, “We’re scientists, not manufacturers,” struck a chord with Thomas, highlighting the industry’s struggle to manage increasingly complex tasks in-house.

This realization mirrored broader challenges across the pharmaceutical sector. Over the following years, Thomas saw how outsourcing to specialized CDMOs became a game-changer. These partnerships allowed biotech companies to focus on innovation while tapping into the advanced infrastructure and expertise of their collaborators.

In the early 2000s, Thomas witnessed the success of this model firsthand when a small biotech client outsourced its manufacturing to a budding CDMO. The move halved development timelines and helped the company navigate regulatory hurdles, showcasing the real potential of these partnerships.

Today, CDMOs are seen as a cornerstone of the pharmaceutical ecosystem. In areas like cell and gene therapy, outsourcing has become essential for staying agile and precise, reflecting the industry’s shift from working in isolation to embracing collaboration.

NorthX Biologics: beyond traditional CDMO services

Within this competitive landscape, NorthX Biologics has emerged as a unique and innovative player. Unlike many of its peers, NorthX Biologics positions itself not just as a traditional CDMO but as an “Beyond CDMO” operating an Innovation Hub offering a range of services designed to support the development and manufacturing of advanced therapies. The company history reflects its deep roots in pharmaceutical manufacturing. Established as the Statens Bakteriologiska Laboratorium (SBL) in 1909, the organization evolved over decades, eventually transitioning into NorthX Biologics in 2021.

NorthX Biologics’ service offering is comprehensive, encompassing microbial and mammalian expression systems, plasmid DNA, recombinant proteins, viral vectors, and cell therapy solutions. These capabilities are underpinned by a robust infrastructure that includes state-of-the-art GMP facilities, advanced analytical laboratories, and flexible cleanrooms. Notably,  a proven track record of regulatory compliance, with multiple successful inspections by the Swedish Medical Products Agency.

One of NorthX Biologics distinguishing features is its focus on advanced therapies, such as cell and gene therapies, mRNA technologies, and personalized medicines. For example, the company has played a critical role in several high-profile projects, including the rapid development of clinical trial materials for novel immunotherapies. In one notable case, NorthX supported HOOKIPA Pharma in scaling up the manufacturing process for a viral vector product, enabling the company to meet tight clinical trial timelines. This project, completed within 18 months, exemplifies NorthX’s ability to deliver innovative solutions under challenging conditions.

Another hallmark is its emphasis on collaboration. The company works closely with clients to understand their unique needs, leveraging its expertise to develop tailored solutions. This collaborative ethos is evident in its work with Mendus, a clinical-stage immuno-oncology company. Together, they established a scalable manufacturing process for Mendus’ lead cell-based therapy, overcoming significant technical and logistical challenges.

When compared to industry giants like Lonza and Catalent, NorthX Biologics differentiation lies in its agility and focus on emerging modalities. While larger CDMOs excel at providing broad, end-to-end solutions, the company offers a more specialized and nimble approach. This is particularly valuable for biotech startups and smaller pharmaceutical firms, which often require customized support to navigate the complexities of advanced therapy development.

CDMOS: a de-risked investment opportunity

The investor perspective on the CDMO sector is overwhelmingly positive. CDMOs represent a de-risked investment opportunity, as their business models are inherently diversified. By serving multiple clients across various therapeutic areas, CDMOs can mitigate the risks associated with individual product failures. Additionally, the sector benefits from strong, long-term societal trends, including an aging population, rising healthcare expenditures, and the growing prevalence of chronic diseases.

For investors, companies like NorthX Biologics signal a forward-thinking approach to pharmaceutical development. The combination of advanced capabilities, collaborative ethos, and focus on innovation positions it as a leader in the rapidly evolving CDMO landscape. The company’s emphasis on advanced therapies aligns with the broader industry trend toward personalized medicine, offering significant growth potential in the years ahead.

Continued growth and transformation

Looking to the future, the CDMO industry is poised for continued growth and transformation. One key trend is the increasing integration of digital technologies, such as artificial intelligence and automation, into manufacturing processes. These technologies have the potential to enhance efficiency, reduce costs, and improve product quality. Another trend is the regionalization of manufacturing capabilities, driven by geopolitical considerations and the need to mitigate supply chain risks.

The pharmaceutical industry is also moving toward a more collaborative ecosystem, where partnerships between CDMOs, biotech firms, and academic institutions play a central role in driving innovation. This shift is particularly evident in the advanced therapy space, where the complexity of products necessitates close collaboration between stakeholders.

In conclusion, the rise of the CDMO era represents a profound shift in the pharmaceutical industry. This transformation has been driven by the need for specialization, efficiency, and collaboration, creating new opportunities for innovation and growth. Companies like NorthX Biologics exemplify the potential of this new paradigm, offering tailored solutions that enable clients to navigate the complexities of advanced therapy development. For investors, the CDMO sector offers a compelling opportunity to engage with a dynamic and resilient industry that is shaping the future of healthcare. As the pharmaceutical landscape continues to evolve, the role of CDMOs will only grow in importance, making this an exciting time for both industry stakeholders and investors alike.