The biopharmaceutical landscape has undergone a remarkable transformation over the past two decades, characterized by a notable diversification in the development of complex molecules. In 2003, approximately 400 antibody-based molecules were in various stages of development, with nearly 90% classified as monoclonal antibodies. Fast forward to 2023, and this figure has surged to over 3,200, with monoclonal antibodies comprising only about 59% of the total. This shift reflects the growing prevalence of bispecifics, multispecifics, and other complex therapeutic molecules, including antibody-drug conjugates, ultimately expanding treatment options for patients with challenging diseases.
As the complexities associated with producing these innovative therapies increase, manufacturers must continuously address the need for effective impurity removal. Complex molecules often present challenges such as reduced stability and lower yields compared to traditional monoclonal antibodies. Moreover, the production processes for these therapies can generate a variety of impurities—ranging from host cell proteins (HCP) to DNA and other process-related contaminants—that complicate downstream processing and impact product quality.
Among the critical aspects of downstream processing is the efficient removal of these impurities, which is crucial for ensuring the safety and efficacy of the final product. Equally important is achieving effective viral clearance, which must be integrated into the purification process to remove any potentially harmful contaminants. Ecolab® has risen to this challenge by developing advanced affinity resins, particularly the Praesto™ Jetted A50 HipH, designed specifically to enhance purification processes for complex molecules, including bispecifics and sensitive antibody formats.
One major benefit of the Praesto Jetted A50 HipH resin is its ability to maintain high yields for pH-sensitive molecules. Traditional protein A affinity chromatography typically utilizes low pH conditions for elution, generally between pH 3 and 3.7. However, these harsh conditions can lead to stability issues and increased aggregation, ultimately reducing yield and increasing the risk of impurities in the final product.
Recent studies, including findings published by Biogen in the Journal of Chromatography (2023), have highlighted the detrimental effects of low pH elution buffers on protein stability. These buffers can lead to increased molecular weight over time due to aggregation. In contrast, the Praesto Jetted A50 HipH resin demonstrated remarkable stability over a 48-hour period when used with higher pH elution buffers, effectively minimizing aggregate formation and enhancing overall yield.
Additionally, investigations by IMCS in the U.S. revealed that yield is significantly impacted by elution pH. The Praesto Jetted A50 HipH showed a much shallower yield decrease at higher pH levels than standard protein A resins. This indicates that this resin excels at maintaining yield within pH ranges of 4 to 5, further reinforcing its role in effective impurity management.
Furthermore, Ecolab's HipH resin enhances impurity removal during the purification process, achieving robust viral clearance in the protein A affinity step. Internal testing demonstrated that the high molecular weight content was considerably lower with the Praesto Jetted A50 HipH, even when purifying challenging bispecifics. This capability is attributed to the resin's mild elution profile, which prevents aggregation and promotes a cleaner product.
What’s particularly noteworthy is that the Praesto Jetted A50 HipH can achieve substantial log reductions in viral clearance that are usually only attainable in post-affinity polishing steps. This not only simplifies the overall purification process but also alleviates some of the burdens associated with downstream steps, making the polishing stage more efficient for complex molecules.
In terms of upstream and downstream processing efficiency, maintaining lower levels of high molecular weight content mitigates the need for additional material loading. This alleviates some of the burdens on upstream processes while improving log reduction rates for host cell proteins when compared to other protein A resins on the market.
Effective process scaling is vital for successful large-scale commercialization of chromatography resins. The features of the Praesto Jetted A50 HipH resin make it well-suited for large-scale manufacturing. Ecolab supports this implementation with hands-on guidance and has dedicated application labs in Wales, UK, and Pennsylvania. Here, customers can collaborate with Ecolab's bioprocess experts to tailor solutions to their specific purification needs.
In conclusion, the advancements offered by the Praesto Jetted A50 HipH resin represent a significant leap forward in impurity removal and viral clearance for the complex molecule market. By enhancing yield, improving stability, and facilitating better impurity management—including robust viral clearance—Ecolab is poised to support the next generation of biopharmaceutical innovation.
