In today’s highly competitive and rapidly evolving global vaccines market, companies are looking for techniques, technologies, and tools to optimize processes, accelerate the timeline for moving candidate vaccines into the clinic, and build flexibility into vaccine production. All of these initiatives seek to enable rapid and reliable scale-up, expedite process validation and regulatory review, and facilitate the transfer of manufacturing technology from site to site and country to country.
The 21st century may be the “new Golden Age of vaccines,” says Catorina Flyborg, Ph.D., leader of vaccine initiatives at GE Healthcare, who will speak about critical process parameters to maximize vaccine yield and quality at the “World Vaccine Congress” next month in Lyon, France.
Dr. Flyborg will compare traditional and disposable manufacturing platforms and describe how to identify the threshold at which it is economical and prudent—based on parameters of quality and quantity—to switch to disposable systems. As vaccines tend to be produced in smaller quantities than most other biopharmaceuticals, disposable production systems offer particular advantages. Dr. Flyborg expects the industry to continue to use a combination of stainless steel and disposable platforms.
Process optimization in vaccine production has many different facets and tends to be more complicated than for monoclonal antibodies (mAbs), for example, due to the greater complexity of the products. A key area for improvement early in the developmental pipeline is boosting expression levels in a cell line of interest to enable smaller volume, more efficient bioprocesses. Scale-up of mammalian cell culture is inherently more difficult due mainly to the need for higher oxygen concentrations. A generic goal for process optimization in vaccine production focuses on reducing water consumption and overall energy use.
Philip Ball, Ph.D., technical director at Eden Biodesign, will talk about end-to-end process development and scalable manufacturing at next month’s meeting. Capacity and scalability are key buzzwords in the industry today, as current vaccine capacity is insufficient, especially for influenza, despite continuing increases in global biomanufacturing capacity, according to Dr. Ball.
“We need transferrable and scalable production platforms,” similar to what has been achieved for mAbs. “I think we can learn from the antibody industry,” he says, in terms of rapid development of robust, transferrable processes for localized production, for which disposable technologies available up to about 2,000 liter scale are ideal. Disposable options are also rapidly expanding beyond the bioreactor and fermentor space and, for example, into purification processes, with growing interest in prefilled chromatography columns and single-use sterile filtration products.
When Dr. Ball speaks of end-to-end process development, he advises vaccine manufacturers to consider process development as part of, and not separate from, the product-development cycle. “Begin with the end in mind,” is Eden’s philosophy, and he encourages clients to understand the end-points of their processes, consider scale-up needs early on, and not look at a single process step in isolation.
Eden strives to apply enabling technologies to maximize flexibility and efficiency. Examples include adapting adherent cell lines to grow in suspension for enhanced scalability in stirred tank reactors. The company offers expertise in a range of expression technologies and culture systems, including microbial, viral, baculovirus, and mammalian.
Novel purification strategies include the use of monolithic membrane absorbers with high binding capacity for both product capture and polishing steps, and a move away from centrifugation to more scalable and transferrable chromatographic techniques. Dr. Ball also describes the adoption of analytical methods and tools developed for the mAb industry, which are improving process characterization and product analysis, including novel HPLC- and mass spectrometry-based methods.