Joining forces to tackle cholera

The urgent need for better cholera vaccines

The World Health Organization (WHO) estimates 1.3–4 million cholera cases and 21,000–143,000 deaths each year, showing that cholera remains a significant global health concern. Cholera is an acute diarrheal disease caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae, disproportionately affecting people in conflict settings, refugee camps and areas hit by climate related disasters. Since 2022, cases have surged and WHO has classified cholera as a Category 3 emergency.

Cholera is a preventable disease and vaccines are available, but it continues to disproportionately impact populations in low- and middle-income countries, where access to clean water and healthcare is limited. Therefore, affordability directly influences the reach and sustainability of vaccination campaigns. Ensuring that vaccines are economically accessible allows governments and humanitarian organizations to protect vulnerable communities at scale, making cost-efficiency a cornerstone of global cholera control efforts. To address this, oral cholera vaccines (OCVs) serve as a vital short- to medium-term intervention, particularly during outbreaks.

From bench to clinic: accelerating DuoChol

Researchers at the University of Gothenburg have developed DuoChol, a dry formulated, inactivated bacterial whole-cell/cholera toxin B subunit OCV. DuoChol consists of three drug substances, which are freeze dried with a stabilizer to produce the powder used for capsule filling.

Unlike liquid OCVs that typically require a cold chain, the dry formulated DuoChol provides improved thermostability enabling the product to remain stable at higher temperatures for longer, simplifying delivery to remote or resource limited settings. The dry format also reduces weight and volume, enabling more sustainable transport.

NorthX Biologics is supporting DuoChol’s development by translating early concepts into scalable, GMP-compliant processes. Working closely with Gotovax and the International Vaccine Institute (IVI), the company applied deep industrial and regulatory expertise to smooth the transition from lab bench to clinical trials.

Building a scalable process on proven capabilities

Co‑designing a fit‑for‑purpose manufacturing flow

IVI and Gotovax asked NorthX Biologics to support the co-design of a manufacturing process tailored to the characteristics of DuoChol. While Gotovax contributed product-specific insights, NorthX Biologics ensured the process met current regulatory standards and was scalable for future industrial use. Small-scale trials were conducted jointly to facilitate seamless technology transfer and knowledge sharing.

Upstream and downstream process development: scalability, speed and efficiency

NorthX Biologics engineered a fermentation process that had not previously been run in a fermenter system. Using Gotovax data, the team designed a scalable upstream process (USP) that maintained performance from lab scale to large clinical scale, achieving identical results. The fermentation strategy delivered rapid, controlled bacterial growth to maximize yield and reduce any batch failure risk. It used an exponential feed to keep growth rate constant and an oxygen transfer‑strategy relying solely on process air, avoiding oxygen supplementation to control cost. By hardwiring cost efficiency from day one, a constant μ via exponential feeding and relying solely on process air for oxygen transfer rate, NorthX Biologics manage to avoid oxygen supplementation and materially reduce cost of goods (COGS) The target product could be produced within one day of fermentation, and the theoretically designed process ran without major deviations in the first GMP batches.

For downstream processing (DSP), centrifugation was replaced with tangential flow filtration (TFF). Replacing centrifugation with TFF in this project de-risked GMP operations by enabling closed processing, gentler handling, and a smaller footprint, which lead to delivering higher recovery at lower cost. Piloted at small scale and then scaled up for clinical manufacturing, the process was designed to be time and cost-efficient with minimal number of purification steps while producing a safe, clinic-ready product. The implemented purification process efficiently removed process related impurities such as antifoaming agents and inactivation reagents.

Risk-based inactivation validation

To accelerate first-in-human (FIH) progress, NorthX Biologics implemented a risk-based approach to inactivation validation. Leveraging small-scale, only a limited number of clinical-scale batches were needed to confirm complete inactivation and ensure patient safety. Validation was performed using methods developed and fully validated in the company’s QC lab, and the inactivation step was integrated into production to shorten overall timelines while maintaining a robust safety margin.

Analytical method transfer and validation

Accurate characterization of the vaccine product is essential to ensure safety and efficacy. Based on its vaccine sector experience, NorthX Biologics established and validated the assay panel required to release clinical material, and standardized selected product-specific analytical methods originally developed in academic labs for compliant QC use. The staff received on-site training at Gotovax, transferred the techniques, and validated methods to a level appropriate for first-in-human use. NorthX Biologics also supported IVI and Gotovax in setting an appropriate release specification for clinical trial material. Taken together, these efforts underscore the importance of transparency and structured knowledge sharing between the manufacturer and the sponsor, enabling phase-appropriate specifications, compliant QC, and a de-risked first-in-human release.

Clinical trial material for DuoChol

Using the developed processes, NorthX Biologics manufactured clinical trial material (CTM) for DuoChol. One batch of each of the three drug substances was sufficient to support clinical studies and two years of stability testing, laying the groundwork for the next clinical phase. To accelerate timelines, NorthX Biologics leveraged manufacturing capabilities at its two sites to progress components in parallel and successfully led the outsourcing of lyophilization and capsule filling to a partner. NorthX Biologics’ Qualified Person (QP) released the material for clinical use, and the team supported IVI and Gotovax in preparing the CMC section of the IMPD for submission to the regulatory authorities.

Result: a collaborative campaign delivering high-quality vaccine material for clinical execution. The process is now built for scalability, quality and cost-effectiveness, addressing the unmet need for an affordable, thermostable cholera vaccine.