By Olivier Loeillot, general manager of enterprise solutions, GE Healthcare Life Sciences
Vaccines have the potential to transform health outcomes on a global scale. Because of this promise, the World Health Organization and biopharmaceutical manufacturers are predicting major growth in the global demand for vaccines over the next decade. Meeting this rising demand for vaccines while simultaneously ensuring a safe and reliable supply of affordable product, produced in an environmentally responsible manner, presents the industry with a number of challenges. Indeed, many manufacturers are beginning to look closely at their production processes, and, as a consequence, we are observing an industry shift away from traditional manufacturing techniques and increased adoption of newer technologies for culture and purification, which can bring significant benefits.
According to Kalorama Information Market Intelligence (Vaccine Production, February 2012), the global vaccine market was approaching U.S. $30 billion in 2012 and is forecast to reach U.S. $35 billion by 2015. While the five top vaccine manufacturers account for more than 80% of global market share, the landscape is changing rapidly. China, with a quarter of the world’s population, is the world’s largest vaccine manufacturer by dose and the fourth largest vaccine market in the world.
Why Chromatography Is Essential To Vaccine Manufacturing
Historically, the vaccine industry has tended not to see chromatography, which is widely used in the production of recombinant protein drugs, as playing a key role in vaccine manufacturing. This is partially due to the success of vaccines using whole cells, acellular fraction, or whole virus and partially due to concerns that antigenicity of purified components might be lost. However, scientific studies have indicated that purified vaccine components are not only effective, but can also be safer with fewer side effects. For example, the pertussis vaccine, which was originally produced using whole cell technology, was initially only reluctantly accepted in spite of its efficacy because of rare but intense adverse reactions caused by toxic components remaining from production. Because of these adverse reactions, the acceptance rate of pertussis vaccine greatly decreased in the early 1970s, leading to many vaccine manufacturers making great efforts to modernize their production methods to include purification and produce a safer vaccine.
Furthermore, many vaccine manufacturing processes involve organic solvent extraction, salt precipitation, and highspeed centrifugation. In addition to the potential negative environmental impact, such processes can result in low efficiency and low consistency in the quality of vaccines. For example, conventional preparation of polysaccharide vaccines for Meningococcus and Pneumococcus uses ethanol precipitation and phenol extraction. The introduction of membrane and chromatography separation technologies can eliminate these steps, resulting in a more efficient and environmentally favorable manufacturing process, as well as higher quality vaccine. This new approach also removed the need for high-speed centrifugation, which is both expensive and inefficient at removing unwanted toxins.
Improved Yield, Shortened Production Times
Another major challenge for many countries globally is that domestic vaccine production cannot meet demand. In China, this is true for many vaccines, including several in the national mandatory immunization program. The annual shortfall for pertussis vaccine, for example, is estimated at 46 million doses. Enhancing the efficiency of the traditional biomanufacturing processes offers the potential to contribute to overcoming this shortage. By switching to purification of acellular components with chromatography, the need for salt precipitation and high-speed centrifugation steps is eliminated, resulting in improved yield and purity, with the added benefit of shortened production times.
New manufacturing technologies and approaches are giving the Chinese vaccine industry the opportunity to improve the efficiency of their manufacturing processes. Such improvements will help China meet vaccine demand, with the added benefit of greater manufacturing efficiency and lower environmental impact. More importantly, the benefits observed in China are likely to be applicable in any country where vaccine manufacturers are still taking a more traditional approach.