By Joakim Lundkvist, GE Healthcare
The biopharmaceutical market has become more industrialized and keeps expanding globally, both in volume and in a variety of products. There is continuous pressure to improve the efficiency and productivity of large-scale manufacturing by using breakthrough purification technologies. Chromatography has always played a crucial role in the purification of biologics. It has constantly evolved, and methods and capabilities have improved to reflect the industry requirements. This article gives an overview of how experience, innovation, and dialogue with customers led to the development of a platform that has revolutionized the economics of large-scale chromatography column packing.
The first industrial-scale chromatography columns were developed in the 1960s and 1970s, when biotechnology was still in its early development. Technical and productivity requirements on columns were limited at the time, but as the chromatography technology developed, so did the columns.
Significant column technology steps were taken in the mid-1980s, with the introduction of so-called packin-place columns. This technology is still widely used today. Column packing using pack-in-place technology was still a very slow, manual, and labor-intensive process. Due to the craftsmanship-like packing and the lack of proper science, biopharmaceutical companies were dependent on a few, highly skilled column packing experts. “Large-scale chromatography column packing at that time was more of an art than science,” says Joakim Lundkvist, Modality Manager for BioProcess™ Hardware at GE Healthcare’s Life Sciences business.
Some of the major setbacks were the varying packing success rate and occasional bed structure failures, which caused unnecessary and costly delays in manufacturing. In addition, a significant excess of chromatography medium was often required, and maintenance was tedious and sometimes hazardous.
Moreover, scale-up required additional development of packing and cleaning methods due to the fragmented column platforms used. This additional scale-up work and knowledge transfer caused longer time to market. In the early 2000s, the newly developed high-flow chromatography media proved to be less compatible with the available column hardware design, especially at the scale of operation that had become a reality. For GE Healthcare, with over 50 years of innovation in the chromatography field, the time seemed right for a holistic approach to solve the challenges facing largescale chromatography packing.
Building a Modern Platform Technology
In order to capture the real market needs, GE Healthcare interacted actively with their customers. The company experts evaluated the bottlenecks in the existing chromatography equipment capabilities and, based on the accumulated knowledge, GE Healthcare decided to evolve the column concept into a completely new platform. This platform would eliminate the drawbacks of the predecessors’ technologies. The goal was to offer a technology that would fit the customers’ needs and ultimately create a cost- and time-effective solution. After extensive experimentation, they developed an optimized method for packing. The packing method was further validated for a wide range of chromatography media, column dimensions, and conditions to create an automated methodology. This way, processes were simplified and the economics of operations improved.
The result was the AxiChrom™ column platform. The major advantage of the platform is the operator-independent and automated packing, using verified preprogrammed methods. This packing technique leads to excellent reproducibility with great long-term bed stability for a wide range of chromatography media. The need for experts is minimized, and repacking and troubleshooting is significantly reduced. Moreover, the scalable design from 50 mm to 1.6 m provides the same excellent packing results across the entire range, which facilitates technology transfer between scales and sites. In addition, it is quick to set up, learn, operate, and change-over, leading to a significant reduction of time and labor. Importantly, it can be integrated into the plant’s distributed control system (DCS).
The benefits are multiple: AxiChrom columns maximize uptime, simplify processes, contribute to the overall economics (see “Comparison of Packing Time Line” chart below), provide solutions for process development through manufacturing, and shorten time to market.
Furthermore, the sanitary design of the AxiChrom columns, including a highly effective liquid distribution system, reduces the risk for bioburden, a key challenge to biopharmaceutical manufacturers. “Our customers cannot afford to take risks,” says Lundkvist. “They need to know they can trust the outcome of their processes, and through our verified AxiChrom platform we can contribute to process reliability, reproducibility, and uptime.”
Since the launch of the AxiChrom platform in 2008, GE Healthcare has accumulated a proven track record with many hundreds of installed units from process development scale to full commercial manufacturing.
Investing in the Future
The purposeful design of the AxiChrom platform has helped overcome many market and business challenges, but the evolution of large-scale column design and column packing has never stopped. As concluded in the 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production from BioPlan, the top trend currently is to improve manufacturing efficiency and productivity. GE Healthcare continues investing in the future and optimizing the platform by working closely with customers globally and monitoring what the market demands. With this knowledge and dedication, GE Healthcare can lead the innovation in downstream processing for better economics and improved productivity.
About Joakim Lundkvist
Joakim Lundkvist has a Master’s Degree in Chemical Engineering from the Royal Institute of Technology in Stockholm, Sweden. He joined GE Healthcare’s Life Sciences business in 2000 and has held various roles; R&D staff research engineer, service specialist manager, marketing manager and currently holds a position as the leader for the Biomanufacturing equipment sales specialist team in Europe within GE Healthcare.
About GE Healthcare, Life Sciences
GE Healthcare’s Life Sciences business provides a wide range of bioprocessing products and services that enable the development and manufacture of high-quality biotherapeutics and vaccines. Using our knowledge and expertise, we support our customers in increasing speed to market, while avoiding unnecessary costs and improving quality and performance in drug manufacturing. As a provider of high-quality products, customized technical and commercial services, as well as design and construction of complete biomanufacturing solutions, we support the biopharmaceutical industry in making health visions a reality.
GE, GE monogram, AxiChrom, and BioProcess are trademarks of General Electric Company.