Viral vaccine manufacturing for clinical trials

Viral vaccines are entering a new era

Vaccines have played a pivotal role in controlling infectious diseases for more than a century. Often regarded as one of the most impactful public health innovations, they are estimated to have saved over 150 million lives in the past 50 years (1). From smallpox and polio to the rapid development of COVID-19 vaccines, the field continues to evolve through advances in technology, manufacturing, and regulation.

Today, viral vaccine development is entering a new era, marked by diverse platforms such as viral vectors, recombinant subunits, and nucleotide-based technologies—including mRNA and DNA vaccines. These platforms offer faster development timelines and more targeted immune responses, supporting both pandemic preparedness and the treatment of rare diseases.

While novel modalities receive significant attention, traditional viral vaccines—often based on live attenuated or inactivated viruses—remain vital. With well-established safety profiles and robust immune activation, they are essential for indications where long-term stability and proven efficacy are critical. For pathogens such as polio, measles, and rabies, these vaccines continue to serve as gold standards. In the case of measles, for example, two doses of an attenuated vaccine provide up to 97% protection in unvaccinated individuals (2).

Supporting public health efforts and future pandemic response requires maintaining the infrastructure, knowledge, and capacity for viral vaccine manufacturing, across both established and emerging technologies.

Moving virus vaccines into clinical testing

Translating early-stage viral vaccine concepts into clinical-grade products involves complex technical and regulatory steps. Laboratory-scale methods often use research-grade materials and manual handling, which must be adapted to GMP standards. This includes qualifying raw materials, validating analytical methods, scaling up bioreactors, and implementing aseptic processing.

For example, virus propagation may shift from T-flasks in preclinical work to fixed-bed or suspension bioreactors at scale—each requiring different process controls and comparability assessments for regulatory compliance with EMA and FDA standards. Early CMC planning is critical to ensure successful clinical entry.

Robust quality systems, tailored to the characteristics of early-stage viral vaccines, must be in place to meet GMP requirements. This includes specialized expertise distinct from that required during discovery phases.

In many cases, biosafety-level (BSL) classified facilities are needed. NorthX Biologics have flexible capabilities for handling of virus strains up to BSL-3. For novel pathogens a conservative “+1” biosafety approach—applying higher-level protocols than officially required—is sometimes used until further safety data are available.

Balancing biosafety requirements with GMP demands presents operational challenges. Systems must simultaneously prevent product contamination and protect personnel from infectious agents—necessitating specialized equipment, validated procedures, and experienced teams.

Viral vaccine manufacturing: A multi-step process

Viral vaccine production involves a series of interconnected steps, beginning with the generation of cell and virus seed banks. These materials must meet GMP standards and align with ICH Q5A and Q5D guidelines.

A Master Cell Bank (MCB), derived from a characterized clonal population, serves as the foundation for a Working Cell Bank (WCB), which is used in vaccine production. Common cell lines include Vero, HEK293, and MDCK, with selection based on virus type, yield requirements, and regulatory considerations. Once established, these banks support scalable vaccine platforms.

Similarly, a Master Virus Seed (MVS) and Working Virus Seed (WVS) are developed for each specific pathogen. These virus seeds undergo rigorous characterization to ensure quality and consistency.

With seed banks in place, vaccine production can begin. The upstream process includes cell expansion, viral infection, and harvest. Culture conditions are tightly controlled, and the virus is harvested following replication. Downstream processing includes cell lysis or filtration, followed by purification steps such as chromatography and ultrafiltration to remove impurities.

For inactivated vaccines, the virus is rendered non-infectious using validated chemical or heat-based methods. Analytical assays confirm successful inactivation. Failures in this step have had historical consequences—such as the Cutter incident in 1955, when incomplete inactivation of poliovirus caused multiple cases of polio.

Advances in synthetic biology now allow for genetically attenuated viruses that retain immunogenicity without requiring inactivation. While traditional approaches remain in use, platforms such as subunit and mRNA vaccines are gaining prominence due to their scalability and safety profiles.

Final formulation includes combining the purified virus with stabilizers, adjuvants, or preservatives to ensure product stability and immunogenicity. Drug substance is aseptically filled into final containers under controlled conditions. Comprehensive in-process controls and final release tests—such as sterility, potency, and stability testing—ensure the vaccine meets all regulatory specifications for clinical or commercial use.

NorthX Biologics: Supporting the development of novel vaccines

NorthX Biologics provides end-to-end support for viral vaccine development, from early-stage process design to GMP manufacturing of clinical-grade drug substance and drug product. The company has contributed to multiple global initiatives, including projects with the World Health Organization and the Bill & Melinda Gates Foundation.

The company’s virus vaccine center of excellence, located in Stockholm near the Karolinska Institute, houses expert teams with experience in various modalities—including live attenuated viruses, recombinant proteins, whole-cell vaccines, and nucleotide-based platforms. During the COVID-19 pandemic, NorthX manufactured virus seed stocks and produced drug substance under BSL-3 conditions, including scale-up from adherent cultures to fixed-bed bioreactors.

The team has also supported clinical-stage arenavirus-based cancer vaccine programs in both Europe and the United States, manufacturing and releasing multiple GMP batches for ongoing trials.

Advancing safe and effective vaccines

Manufacturing viral vaccines for clinical trials involves unique challenges, particularly in balancing biosafety, regulatory compliance, and production scalability. Success requires early alignment between discovery, process development, and GMP manufacturing.

By drawing on its proven track record and cross-functional expertise, NorthX Biologics supports the advancement of safe and effective vaccines targeting both common and emerging infectious diseases. As global demand continues to grow, the company remains committed to enabling innovation in vaccine development and contributing to public health worldwide.

References:

1. https://www.who.int/news/item/24-04-2024-global-immunization-efforts-have-saved-at-least-154-million-lives-over-the-past-50-years/
2. https://www.cdc.gov/ncird/downloads/immunization-highlights.pdf