Navigating the complexities of microbial and mammalian manufacturing

With a rich historical legacy and decades of expertise at its two sites, NorthX Biologics has long mastered the complexities of microbial and mammalian manufacturing. By offering capabilities and differentiating experience in both expression systems, NorthX Biologics provides tailored, cost-effective solutions that optimize processes and meet the diverse needs of recombinant protein production.

Authors: Peter Boman, Chief Operations Officer, and Helena Pettersson, Chief Production Officer, Head of USP, NorthX Biologics

Distinct approaches in biomanufacturing: mammalian cell culture vs. microbial fermentation

In biopharmaceutical manufacturing, mammalian cell culture remains a dominant method, commonly utilizing Chinese hamster ovary (CHO) cells for producing protein-based drugs and human embryonic kidney (HEK) cells for viral vectors. However, microbial fermentation, which employs bacteria like Escherichia coli and Pseudomonas fluorescens, as well as yeasts like Saccharomyces cerevisiae and Pichia pastoris, is gaining traction, especially with the rise of new modalities, such as nucleic acids, single-domain antibodies, peptidbodies, and antibody fragments.

One of the main advantages of microbial fermentation is speed. Whereas mammalian cell culture processes can take six weeks or more from start to purified drug substance, fermentation processes are typically completed within a few days. Additionally, mammalian cells require complex and costly media formulations — often containing up to 100 ingredients — while bacteria and yeast need only simple glucose-based feeds. Microbial systems also tend to express target substances at higher concentrations than mammalian cells, further enhancing their appeal for specific applications.

However, bacteria and yeast have limitations. They are generally inefficient at producing larger recombinant proteins and monoclonal antibodies, making them better suited for smaller biologics, such as peptides, cytokines, and growth factors. Furthermore, microbial systems lack the capacity for extensive post-translational modifications (PTMs), such as glycosylation, which restricts their use in applications that require these modifications, including the prevalent monoclonal antibodies. Mammalian cell culture, therefore, is often the preferred option for these more complex requirements, as it provides the capabilities that microbial systems cannot.

The capability to offer both mammalian cell culture and microbial fermentation allows a comprehensive contract development and manufacturing organization (CDMO) like NorthX Biologics to better tailor production processes to the unique needs of each biomolecule. Advances in fermentation technology enable the efficient and cost-effective production of smaller and less complex biologics, while innovations in mammalian cell culture, such as enhanced titers and improved process control, support the manufacture of more complex biomolecules requiring intricate post-translational modifications. By leveraging expertise in both systems, forward-thinking CDMOs can provide optimized, high-quality solutions across a broad range of biologics, ultimately delivering greater value to their clients.

Matching biomolecules to manufacturing systems

Choosing between mammalian cell culture and microbial fermentation for biopharmaceutical production requires a balance of financial, technical, and quality considerations. The optimal manufacturing system for a drug candidate depends primarily on the unique characteristics of the biomolecule, including its size, complexity, and need for PTMs, as well as the intended use of the final product.

For some biomolecules, production in mammalian cells is necessary due to their capacity to perform complex modifications, while other substances are more efficiently produced through microbial fermentation. In certain cases, a highly sensitive protein may benefit from fermentation’s shorter production timeline, which can reduce the risk of degradation. Quality standards also vary across products, with some requiring exceptionally high purity that may be easier to achieve with one system over the other.

Ultimately, understanding these specific requirements early in the development process helps ensure that the chosen manufacturing path is both efficient and cost-effective.

Advances in mammalian bioproduction: higher titers and enhanced control

Mammalian cell culture has seen remarkable advancements over the past two decades, most notably a significant increase in production titers. While titers of 0.1 grams per liter were typical when biologics first entered the market, today’s processes commonly achieve titers of 10 grams per liter or higher. This leap has been driven by a deeper understanding of cellular mechanisms and the adoption of automation and digitalization in biomanufacturing.

Process analytical technologies now enable real-time monitoring and control, providing insights that have propelled improvements in cell-line engineering and media formulation. These innovations allow biopharma companies to better optimize mammalian cell culture processes, enhancing both productivity and efficiency.

Enhancing fermentation efficiency: optimizing strains and streamlining processes

Recent advancements in bacterial and yeast expression systems have focused on increasing efficiency and reducing production costs. New microbial strains now allow for more effective expression across a broader range of proteins, expanding the applicability of fermentation. Additionally, significant improvements in downstream processing have been achieved, as this stage traditionally accounts for a large portion of the cost of goods in biologics manufacturing.

One of the primary goals in downstream optimization has been to minimize the number of costly chromatography steps. Techniques such as heat inactivation and precipitation are now used to simplify protein purification, offering a more cost-effective and efficient approach to removing undesired proteins. These developments make microbial fermentation a more competitive option for producing biologics.

Accelerating bioprocessing with AI-driven efficiency

Optimizing bioprocesses, whether through mammalian cell culture or microbial fermentation, involves extensive and costly screening of cell lines and process parameters. Today, digitalization — particularly through artificial intelligence (AI) and machine learning (ML) — is transforming this process by enabling biopharmaceutical scientists to work more efficiently and effectively.

With adequate data, AI and ML algorithms can streamline the design of complex studies, such as design-of-experiment (DoE) frameworks, helping researchers reduce preparation time and gain richer, more actionable insights. These digital tools allow for smarter process development, accelerating the pathway to optimized production for both traditional and emerging biomanufacturing systems.

Trusted expertise in mammalian expression at NorthX Biologics

Although formally established in 2021, NorthX Biologics draws on decades of biological manufacturing expertise, emerging from a combination of legacy entities. The company’s mammalian cell culture capabilities expanded significantly with the acquisition of a specialized development and manufacturing facility from Valneva in Stockholm, Sweden, bringing a team of experts in mammalian process development, GMP manufacturing, and state-of-the-art equipment.

This site has a rich history, including the production of Sweden’s first inactivated polio vaccine. Later, it contributed to global eradication efforts through collaborations with the World Health Organization and the Bill & Melinda Gates Foundation. In addition to its robust protein and antibody production capabilities, NorthX Biologics has demonstrated expertise in handling high-risk viruses. The Stockholm facility features high-containment, multipurpose biosafety infrastructure, enabling the safe production of drug substances for pandemic-related viruses, including the highly contagious SARS-CoV-2.

NorthX’s clients benefit from close collaboration with scientists who bring deep process knowledge from development through to commercial production. With extensive experience in process development and scale-up, the team at NorthX Biologics ensures that manufacturability is built into each project from the start, helping clients avoid potential challenges during GMP implementation.

Furthermore, NorthX Biologics is well equipped to support comparability studies for products transitioning from early to late-stage clinical trials, ensuring continuity and consistency. Transparency and open communication are foundational to NorthX’s approach, fostering trust both within the team and with clients. NorthX’s clients know they can rely on the company for timely, complete, and quality-driven delivery.

Microbial fermentation expertise at NorthX Biologics

NorthX Biologics’ Matfors, Sweden site has been manufacturing proteins through microbial fermentation since the early 1990s. While the site has a long history in biologics production, it transitioned to a multiproduct contract manufacturing organization in 2005 and has since undergone continuous investment to expand its capabilities. These include fill/finish services, high-quality plasmid manufacturing, enhanced quality control capabilities, and large-scale protein purification with single-use fermentation suites.

The facility supports a wide range of bacterial fermentation using both anaerobic and aerobic strains and is equipped to handle risk group Level 1 and 2 organisms in Matfors, as well as up to risk group Level 3 organisms at the Stockholm biosafety facility. With extensive in-house analytical and quality assurance capabilities, including QA/QP services and analytical development expertise, NorthX Biologics ensures rigorous oversight across all production stages.

Different strains present unique challenges—some produce lower yields due to limited growth density, while others, like cholera strains, can complicate product purification. With decades of experience as a service provider, NorthX’s team excels at addressing these complexities. They are adept at identifying the ideal strain for each project and tailoring fermentation and lysis methods to achieve optimal results.

NorthX’s facility is designed to accommodate both small-volume production for early-phase studies and large-scale manufacturing for late-stage trials. In high-demand situations, the team is capable of operating on a 24/7 schedule to meet client needs. Supported by experienced project managers with deep expertise in multiproduct facility operations, NorthX Biologics ensures seamless execution across diverse biomanufacturing demands.

Who benefits from partnering with NorthX Biologics?

At NorthX Biologics, our commitment goes beyond being a trustworthy CDMO; we strive to be a true partner in innovation, sustainability, and excellence. Our Innovation Hub in Matfors showcases our dedication to advancing cutting-edge technologies that not only benefit our customers but ultimately improve outcomes for patients worldwide. With a problem-solving mindset and customer-first approach, we support clients at every stage of their journey — from grant writing to navigating the complexities of biologics manufacturing.

NorthX Biologics offers a unique value proposition as a multipurpose, one-stop-shop CDMO. We combine our dual expertise in mammalian and microbial manufacturing with extensive in-house capabilities in analytical development, quality assurance, and large-scale production. This comprehensive service portfolio allows us to streamline drug development and manufacturing, enabling faster, more efficient, and cost-effective solutions for pharmaceutical and biotech companies.

Sustainability is deeply embedded in our operations. We actively collaborate with dedicated sustainability personnel and adhere to guidelines from Swedish authorities to become an increasingly eco-friendly organization. Powered by green electricity and sustainable practices, we are working toward reducing our environmental footprint while maintaining the highest levels of quality and compliance.

Sweden’s reputation for excellence extends to our highly educated workforce, whose expertise ensures the delivery of superior results. Clients benefit from our commitment to delivering products on time, in full, and with exceptional quality. This dedication applies whether you are a small or medium-sized drug developer working on complex, niche, high-value therapeutic candidates or a large biopharma company seeking a reliable CDMO partner for scalable production.

Choosing NorthX Biologics means choosing an experienced, innovative, and sustainable partner that is ready to meet your needs at every stage, from early development to commercialization. With Swedish precision and a proven track record, we deliver high-value solutions that inspire confidence and enable success.

Peter Boman
Chief Operations Officer
NorthX Biologics

Peter is the COO at NorthX Biologics, and as such responsible for our manufacturing facilities in Matfors. He holds a master’s degree in engineering, biotechnology, and business administration. Peter has worked in research and development with complex sample analytics, analytical development, and cell culture process development. He joined NorthX in 2013 and has since continuously improved his talented team, resulting in the production of a large number of biological drugs for clinical trials.

LinkedIn

Helena Pettersson
Chief Production Officer, Head of USP
NorthX Biologics

Helena is CPO at NorthX Biologics as well as Head of Upstream at our Stockholm site. She holds a master’s degree in chemical engineering, biotechnology from Mälardalens University. With former roles as scientist in process development at Pharmacia, CMC development at SOBI, and leadership in process development at Crucell, Helena brings more than 25 years of experience. She manages a highly skilled and experienced team, making sure we are on top of the advanced therapeutics sector.

LinkedIn