An intensified manufacturing process, initially developed to support the production of an Ebola vaccine for a Phase II trial in Uganda, could revolutionize vaccine manufacturing during health emergencies. According to ReiThera, an Italian CDMO, this process significantly accelerates vaccine production by increasing volumetric productivity.
Enhanced Cell Culture Techniques
Stefano Colloca, CEO of ReiThera, explained that the intensified process focuses on maximizing productivity per unit volume. This is achieved by optimizing culture conditions that allow a HEK-293-derived packaging cell line to grow at high density. "This was achieved by including, in the fermentation process, a perfusion step carried out in a stirred tank bioreactor. This change resulted in a four-fold increase in production yield," Colloca stated.
Further modifications to the HEK-293 cell line included the insertion of a transcriptional repressor to shut down transgene expression, enhancing genetic stability. The cell line was also adapted to grow in suspension, facilitating faster and more scalable manufacturing compared to traditional methods.
Streamlined Production Process
The production process is designed for scalability in a stirred tank bioreactor, utilizing a packaging cell line adapted to suspension. This is followed by an extensive purification process that combines depth filtration, ultrafiltration, and two chromatography steps. A selective precipitation step for host cell DNA, preceding endonuclease digestion, ensures efficient removal of host cell DNA.
"The entire production process—both upstream and downstream—is mainly conducted using single-use technologies in order to facilitate accelerated changeover between production campaigns," Colloca added.
Ebola Vaccine Development
ReiThera utilized this process to manufacture 20,000 doses of an Ebola vaccine for a Phase II study initiated by the Sabin Vaccine Institute (SBI) in Uganda. The vaccine, based on the ChAd3 simian adenoviral platform, demonstrated promising results in a Phase I clinical trial. Moreover, 1,100 doses were used as an emergency measure to help contain an Ebola outbreak in 2022, according to the SBI.
"Manufacturing took place at ReiThera’s facility located south of Rome, close to the international airport," Colloca noted, adding that the company is preparing for commercial production of the vaccine.
Broader Applications
ReiThera intends to apply this intensified production process more broadly. "The strategy implemented by ReiThera for manufacturing and accelerated lot release can be used for other platform technologies in an emergency situation," Colloca concluded, highlighting the potential for this process to enhance vaccine production across various platforms during future health crises.
