Production of a Bevacizumab Biosimilar Using Continuous Manufacturing Practices; The Approval of Bt Cotton and Its Impact on Agrarian Society in India

From the beginnings of civilization, humans have been continually pursuing better crops and animals using selective breeding. While this gave us the crops that we know now, this process is slow in nature. The ability to edit the genomic sequences of organisms is a technology that has only been available to humans recently but has caused a significant impact on our world. Now, humans can accurately modify organisms to their choosing by selectively adding and removing genomic information – producing organisms with new traits and characteristics. In my capstone project, I will analyze two outcomes of genetic engineering. On one hand, with my technical project, I will be investigating how genetically modified cells can be used to our advantage to produce life-saving therapeutics at a lower cost. With my Science Technology and Society (STS) research paper, I intend to evaluate a different angle of genetically modified organisms. Instead of evaluating the impacts of genetically modified crops directly, I will investigate how the approval process for such technologies can affect its introduction into a new market. In the end, my goal for both papers are to add to the discourse of genetically modifying organisms. As it is such a gray and complicated subject, it is valuable to have multiple different angles to view such a topic from to gain a more holistic understanding.

One area where genetically modified organisms have played a crucial role in benefitting our society is in the production of life-saving medicines. While the first drugs, known as “small molecules,” were primarily synthesized through chemical reactions, “biologics” represent a new form of medicines that can treat new indications but also holds new manufacturing challenges. The largest challenge in producing biologics is that, due to their size and complexity, they are difficult or expensive to create through traditional chemical reactions. Instead, it is easier to leverage a cell’s ability to produce proteins and other biological molecules. This is the crux of recombinant manufacturing. A specific type of cell, in our case a Chinese Hamster Ovarian cell, is selected as a manufacturing platform and then modified so that it can produce the intended drug. After growing and harvesting the drug, oftentimes known as the “upstream” portion of recombinant manufacturing, these proteins must be purified so that they contain no cellular debris or contamination – oftentimes referred to as the “downstream” process.
The purpose of this capstone design project was to develop a continuous manufacturing facility in Durham, NC, to produce bevacizumab. Bevacizumab was initially introduced to the market under the brand name of “Avastin”, produced by the biotechnology company “Genentech”. It was intended to treat various cancers and related conditions, including metastatic colorectal cancer, non-small cell lung cancer, glioblastoma, renal cell carcinoma, cervical cancer, and ovarian cancer. Bevacizumab works by targeting the human vascular endothelial growth factor (VEGF) protein, which plays a crucial role in cell functions and the formation of new blood vessels (angiogenesis). By binding to VEGF and stopping this process, tumor growth is suppressed. This occurs since the tumors are unable to interact with receptors on the blood vessels that it requires for proliferation. Avastin was introduced by the FDA in 2004 and proved to be an effective treatment however its high cost was a barrier for patient to access these benefits.
Now that the drug has gone off patent, this makes way for biosimilars – or biologics that have similar efficacy as the original biologic. Biosimilars are important for several reasons. One of the most important reasons why biosimilars are beneficial is that it introduces competition into the market and drives down the cost of the treatment. This reduces the barrier for access for patients that require this life-saving therapeutic. Furthermore, the increased competition challenges pharmaceutical companies to design more efficient processes that reduce on unnecessary steps and implement better processes. Ultimately, our goal is to design a process that will be capable of produce a biosimilar of Avastin at an affordable and sustainable price for our process. In doing so, we will not only be designing the process itself and all the technical details that accompany it, but we will also perform analysis on how the project itself will fair economically under a variety of conditions. Through this capstone, we hope to demonstrate the possibility of creating treatments that are more affordable yet sustainable for a potential company.

 
Another technology that has incorporated itself into our society under the umbrella of recombinant technology is genetically modified crops. From soybeans to corn, GMOs have inevitably made it to markets around the world. However, these crops only have been a part of our society for a short period of time and understanding the introductory period where new strains of GMOs were being incorporated into our lives is vital to understanding how future instances of recombinant technology could be handled. One of the most prolific introductions of GM crops to a new market was the inception of Bt Cotton into India. Bt cotton incorporates pest resilience into the crop itself by utilizing the genes of the bacterium, Bacillus thuringiensis. In doing so, Monsanto, the creator Bt cotton claimed that the crop would have better yield, reduce the need for harmful pesticides, and ultimately benefit farmers using the new strain. While the technology was first commercialized within the United States, gaining a foothold in foreign market proved a bit more difficult. Within India, Monsanto saw an opportunity to spread its technology overseas. However, in practice, the introduction of this new technology ran into rocky adoption and faced controversies regarding the high cost of seeds, the lack of yield compared to native strains, and unsuitability in the new environment. Many point to the approval process for the crop as the reason for these issues. They claim that there was a lack of transparency, rigor, and inclusion of public needs within the approval phase. By investigating this approval process, I hope to gain a better understanding of this phase of a technology’s lifespan ultimately impact its reception by its intended consumers and audience.

School of Engineering and Applied Science

Bachelor of Science in Chemical Engineering

Technical Advisor: Eric Anderson

STS Advisor: Kent Wayland

Technical Team Members: Dedra Dadzie, Douglas Fox, Morgan-Elizabeth R. McKnight