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Doctoral student Sai Vivek Prabhala receives travel award to present research

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Prabhala, Sai Vivkek
Doctoral student Sai Vivek Prabhala

Sai Vivek Prabhala, a fourth year CBE PhD candidate in Dr. David Wood’s laboratory, was invited to present his research, supported by a travel award, at the annual meeting of the Society for Industrial Microbiology and Biotechnology (SIMB). The meeting will be held July 30-August 2, 2023 in Minneapolis.

Prabhala will make his presentation, in which he will present the latest results of the split intein affinity chromatography technology developed in the Wood Laboratory, during the session titled, “Advancements in process development and engineering for manufacturing of pharmaceuticals."

In his talk, Prabhala will cover case studies detailing the technology’s applications for industrial scale purification of biopharmaceuticals currently on the market and also discuss a few emerging therapeutic modalities.

Prabhala, who was both pleased and surprised to have received an invitation to speak at the conference, was even more delighted to learn that the conference organizers, who found Prabhala's research to be both timely and compelling, had decided to offer him a travel award in support of his upcoming trip to the conference.

The overarching goal of Prabhala's research is to develop scalable chromatography platform technologies for industrial bioseparations. Biopharmaceuticals are a broad category of therapeutics which include monoclonal antibodies for immunotherapy, insulin, and insulin analogs for treating diabetes, hormones, growth factors and recombinant proteins which are currently being used for treating chronic conditions such as hepatitis, melanoma, sarcoma, Crohn’s disease and many other ailments.

A major problem encountered during manufacturing of many of these therapeutic proteins is that each therapeutic protein needs its own custom-made purification process, including multiple chromatography and filtration steps for obtaining a pure enough drug substance from the cell culture that can pass FDA scrutiny and be given to patients.

When these drugs are discovered in the lab, they are often purified using affinity tags which can give relatively pure protein a single step. However, these tags need to be removed before testing the drugs in animal models and humans because they can trigger immunogenic responses. Lab scientists often use proteolytic enzymes to cut off the tags, but these enzymes are very expensive and cannot be used at industrial scale because of cost and efficiency considerations. This necessitates multiple chromatography column-based processes for industrial therapeutic protein purification. The use of multiple columns, membranes and buffers contributes to the high cost of these therapeutics. For instance, the downstream process for monoclonal antibodies often accounts for 80% of the process cost. All these issues result in higher process development costs, delays in getting the drug to the market and higher overall drug costs.

For monoclonal antibodies used for immunotherapy, biochemical engineers have developed the Protein A chromatography platform process (this platform process works for all therapeutics which are similar to monoclonal antibodies), which hastens process development and results in shorter process development timelines. As this is a well-defined platform process, any new monoclonal antibody therapeutic can be purified using the same sequence of unit operations with some limited optimization.

No such approach exists for other non-monoclonal antibody therapeutics. The split intein chromatography technology developed by the Wood Lab is capable of filling this gap. In a single step, Prabhala and his labmates have been able to obtain >99% pure therapeutic protein products from different host organisms such as E. coli and human embryonic kidney (HEK293) cells. This approach offers a seamless transition from drug discovery to process development to manufacturing, thus reducing process development timelines.

Further, this approach results in purified therapeutics that meet all the desired specifications in a process comprising one to two chromatography columns--a significant improvement over the currently used processes. This approach can also result in process savings which can contribute to lower drug manufacturing costs.

Sai Vivek Prabhala and poster
Prabhala won Second Place for Best Poster at the 2022 Graduate Research Symposium.

Prabhala, who won Second Place for Best Poster in the Fall 2022 Graduate Research Symposium (GRS), hopes to work  as a downstream process development scientist in the biopharmaceutical industry after completing his doctoral degree. This role is directly related to his current doctoral work and involves developing scalable purification processes for upcoming protein therapeutics for treating diseases.