Revolutionizing Downstream Processing - Connecting TFF and Chromatography

Introduction

In the biopharmaceutical industry, the downstream processing of biomolecules has always been a complicated task. One particularly challenge was the integration of tangential flow filtration (TFF) batch step with chromatography processes. The variance in pressure and flow requirements between these two methods has historically led to numerous complications and failures. This blog post explores two innovative process configurations recently introduced that promise to revolutionize the way TFF is connected to chromatography, whether pre- or post- chromatography step it is.

The Challenge of TFF and Chromatography Integration

The traditional understanding of downstream processing has made it clear that TFF and chromatography have unique demands. TFF operates under flow recirculation conditions that often do not align well with the more flow rate sensitive environment typically required for chromatography. This mismatch has resulted in many failed attempts to combine these vital processes into a seamless workflow.

Many efforts have been made to place filtration processes, such as TFF or depth filtration (NFF), before chromatography without significant success. Similarly, attempts to use TFF post-chromatography have been fraught with complications. Factors such as pressure differentials, flow rates, and the specific nature of the biomolecules being processed have posed barriers that hindered this integration.

Innovative Process Configurations

Recent developments have led to the introduction of two innovative configurations that provide a viable solution to this longstanding challenge. These configurations enable the successful connection of a TFF or normal flow filtration (NFF) step before or after a chromatography step, thereby enhancing the overall process performance.

The implications of these advancements are significant. By allowing TFF to be effectively utilized both before and after chromatography, bioprocess engineers can expect to see significantly reduced equipment footprint, combined batches with shortened processing time, and typically improved yield and purity of final product. For instance, incorporating TFF prior to chromatography can eliminate the need for a separate buffer exchanging batch step typically required before a chromatography process, resulting in significant saving in manufacturing cost.

Moreover, implementing TFF in post-chromatography configurations offers an efficient way to polish the product, capturing residual contaminants such as virus that may have evaded the chromatography steps. This dual capability again combines two batch steps together making downstream processing not only more efficient but also more cost-effective, allowing for a re-evaluation of existing methodologies.

Future Implications of Connected Batch for Biopharmaceuticals

The introduction of these innovative configurations is poised to transform the landscape of downstream processing in the biopharmaceutical industry. By enabling effective integration of TFF and chromatography, companies can optimize their operations, thereby reducing time and costs associated with manufacturing of biopharmaceutical drugs.

Ultimately, the capability to seamlessly connect TFF and chromatography paves the way for more robust and flexible processing solutions. The future of biopharmaceutical development may very well hinge on such innovations, leading to more efficient manufacturing processes and the production of higher-quality therapeutic proteins and vaccines.