Deep Roots: A Journey Through the Influence of Chromatography on the Biopharmaceutical Industry

Representatives from Tosoh Corporation and Tosoh Bioscience perform the traditional Japanese kagami-biraki ceremony to celebrate the opening of the company’s Ca⁺⁺Pure-HA production facility in Grove City, OH.

The biopharmaceutical industry as we know it today dates back to the late 19th century. Emil von Behring and Paul Ehrlich, among other scientists, were pioneers in the industry. Their work on serum therapy laid a foundation for the development of vaccines and immunotherapies.

The modern biopharmaceuticals emerged in 1973 with the advent of recombinant DNA technology. That groundbreaking discovery opened doors to new frontiers, enabling scientists to manipulate an organism’s DNA for manufacturing novel biological products. The fruits of such revolutionary technology first were borne out with the production of biosynthetic insulin in 1978, which forever changed the landscape of the pharmaceutical industry.

Over the ensuing decades, combining an ever-growing understanding of biology with advances in biotechnology spawned a diverse array of biotherapeutics. Monoclonal antibodies (MAbs), vaccines, recombinant proteins, and gene therapies are some of the products that have helped to form an expanding arsenal in society’s battle against life-threatening diseases. Biopharmaceuticals continue to push the frontiers of what is possible in healthcare.

The Evolution of Downstream Processing
Parallel to the evolution described above has been an equally impactful transformation in the field of downstream processing (DSP). Over the past four decades, the DSP landscape has shifted dramatically, moving from rudimentary and labor-intensive processes to highly advanced automated systems. Chromatography has been instrumental to the biopharmaceutical industry. Its simplicity, flexibility, and efficacy have made it the cornerstone of purification processes for biologic drug molecules.

The technology has come a long way from its early days of simple paper chromatography to the advent of high-performance liquid chromatography (HPLC) and ultrahigh-performance liquid chromatography (UHPLC) for analytical applications. Recently, the emergence of multicolumn chromatography (MCC) as a better alternative to batch chromatography for process applications reflects the growth trajectory and technological innovation within the bioprocess industry. That evolution hasn’t just paralleled the biopharmaceutical industry’s progress; it has actively shaped it. No biotherapeutics could have been commercialized without chromatography to help ensure a high level of safety for patients with production costs that make large-scale production economically feasible.

Tosoh Bioscience Emerges As a Full-Solution Supplier
In recent years, Tosoh Bioscience has metamorphosed from a consumables provider to a full-solution supplier. That strategic shift is exemplified by the introduction of Octave MCC instruments and SkillPak columns to the company’s portfolio, representing great effort to align with the evolving needs of the biopharmaceutical industry.

By diversifying from a provider of chromatography resins and columns to a comprehensive downstream-solutions partner, Tosoh Bioscience not only has broadened its offerings, but also has deepened its expertise. This evolution positions the company as an essential partner for biopharmaceutical developers, offering innovative solutions and recognized support in their mission to deliver life-changing therapies to the patients who need them.

Spotlight on Innovation: The ECOnti Project
Tosoh Bioscience’s evolution has lead to, among other things, the ECOnti project — for continuous manufacturing with Escherichia coli. This multidisciplinary consortium brings together Tosoh Bioscience, enGenes Biotech GmbH, the University of Natural Resources and Life Sciences (BOKU in Vienna, Austria), Qubicon AG, Novasign, and SimVantage to develop a fully integrated and automated continuous upstream and downstream process at up to 10-L batch size. Tosoh Bioscience’s contribution leverages advanced Octave BIO technology and the company’s expertise in continuous DSP.

That small-scale development platform will enable biopharmaceutical companies to develop continuous bioprocesses, implement model-predictive control, and perform economic modeling to demonstrate potential cost savings of continuous manufacturing over batch-based processes. The technology developed through the ECOnti project is expected to offer several key advantages: e.g., enabling use of smaller production facilities, providing for reduced water and energy consumption, and helping companies to limit their CO₂ emissions. The resulting process technologies should put end-to-end process control, full digitization and automation, higher product yields, and enhanced process stability within reach for the biopharmaceutical industry.

Challenge: Adoption of New Technologies
Despite all those advancements, regulated industry’s rate of adopting new technologies remains low. Tosoh Bioscience is mitigating that issue by adopting a collaborative approach. We work closely with industrial partners to ensure that our solutions meet the needs of end users. A recent example involved one of the largest global contract development and manufacturing organizations (CDMOs), Catalent Pharma. Collaboration with them allowed us to optimize both hardware and software for an Octave PRO skid for good manufacturing process (GMP) operations to speed up MCC implementation at the strictly regulated clinical-materials production stage.

As regulatory agencies urge the biopharmaceutical industry to adopt new technologies that will enhance safety and reduce the costs of bioprocesses, the need for alignment between the industry and its suppliers becomes urgent. Therefore, Tosoh Bioscience participates in BioPhorum workstreams, which provide an open forum through which industry leaders openly discuss and address emerging trends and challenges.

Moreover, providing a comprehensive training program facilitates the adoption of innovative solutions. Our “Tosoh Tuesday” webinar series and renowned chromatography workshops demonstrate Tosoh Bioscience’s commitment to smoothing the customer journey. Through such initiatives, we intend not only to pioneer new solutions, but also to drive their adoption.

Toward Continuous Manufacturing and Security of Supply
As we look to the future, the dawn of continuous bioprocessing appears imminent. Investments in MCC and prepacked columns for biomanufacturing are set to define the biopharmaceutical industry’s progress. Tosoh Bioscience’s heavy investment in those areas, which will culminate in the addition of two dedicated manufacturing plants by the end of 2023, reflects the company’s commitment to that vision.

Ensuring business continuity for our customers is critical to preventing supply-chain disruptions related to political, economic, or sanitary crises. Tosoh Bioscience already has expanded its production capacity of chromatography media several times over recent years. Opening a dedicated plant for the proprietary Ca⁺⁺Pure-HA hydroxyapatite product in Grove City, OH, is just one of the latest milestones in expanding our production capacity. The company plans to add media- and equipment-manufacturing sites in several locations in Japan and the United States over the next few years. Doing so will help provide the biopharmaceutical industry with the necessary confidence to implement such media and instruments in manufacturing processes that require stable supplies of high-quality solutions through the decades to come.

In this age of continuing evolution and innovation, Tosoh Bioscience is prepared not just to adapt, but to lead the way. As a full-solution supplier with decades of expertise in chromatography, the company has exciting potential for providing industry leadership, technical expertise, and innovative solutions. Thus, Tosoh Bioscience is set to drive transformation of the biopharmaceutical industry and help to enhance patient access to life-changing therapies.

Our innovative solutions represent one key outcome of the most important developments within the biopharmaceutical industry. The foundation for those innovations always has been and will remain the collective efforts of experts from academia, the biopharmaceutical industry, and biotechnology solution suppliers looking for new and safe ways to improve the manufacturing processes of biotherapeutics.

Dr. Romain Dabre is senior manager of global product management at Tosoh Bioscience GmbH in Griesheim, Germany; [email protected].