Continuous Integrated Bioprocessing: A Prospective Revolution in Biotherapeutics?

Biotherapeutics, crucial for treating cancer and various diseases, are often financially out of reach for many in India due to the exorbitant costs. These are primarily derived from living cells and offer innovative treatments with promising results. However, their production relies on complex and specialized techniques, leading to increased manufacturing costs. In this landscape, Prof Anurag Singh Rathore from IIT Delhi, winner of the TATA Transformation Prize 2023, has pioneered a project that aims to bring the cost down by 50-75%, which will help accessibility of biotherapeutics to seep into the poorer strata of the country, and indeed, transform the world of biotherapeutics as we know it.

The current method of manufacturing biotherapeutics, known as Batch Processing, contributes significantly to these high costs. Batch Processing, while widely used, is associated with inefficiencies that drive up production expenses. This approach often leads to longer processing time, low yields, and significant resource utilization, all of which contribute to elevated costs per unit.

These manufacturing challenges ultimately impact patient accessibility. The high production costs associated with biotherapeutics are often passed down to consumers, rendering these life-saving treatments financially unattainable for many individuals in India, particularly those from lower socioeconomic backgrounds.

In Batch Processing, materials undergo sequential steps, with each step followed by storage and offline analysis. While this approach has been the norm, it poses significant challenges. Extensive equipment and storage space are required, leading to extended processing times and high manufacturing costs. Consequently, the end result is often an exorbitant price tag attached to biotherapeutic products, making them financially out of reach for many patients. For instance, a single injection vial can cost anywhere from 5,000 to 1,00,000 rupees, further establishing the pressing need for a more cost-effective manufacturing method.

And there is an alternative to it. Though it is not a new method and has been in talks for the last decade, it is ambitious and is called Continuous Integrated Bioprocessing, a transformative approach that promises to revolutionize biotherapeutics manufacturing. In this innovative process, all unit operations are seamlessly integrated into a continuous flow, eliminating the need for storage and offline analysis after each step. This streamlined approach not only reduces processing time but also significantly cuts down on manufacturing costs. But the more pressing question is if the quality is compromised. “It increases product consistency and quality because you’re not stopping after each step, but we have not done this for biotherapeutics.”, says Prof. Rathore, who has been working in continuous bioprocessing for the past few years. In 2023, he was awarded the prestigious TATA Transformation Prize for developing the first-ever continuous manufacturing facility in academia at IIT Delhi. This lab is a possible precursor to the future of advanced bioprocessing in India.

Projections suggest that Continuous Integrated Bioprocessing could slash manufacturing costs by an impressive 50-75% and increase productivity by 10-15%, claims Prof Rathore, making biotherapeutics more accessible and affordable for patients worldwide.

However, the biologics industry is cautiously approaching continuous manufacturing, primarily due to several barriers hindering its widespread adoption by large companies. These obstacles include challenges in establishing a compelling business case, largely attributed to existing legacy infrastructure. These companies have already put a lot of money into using upstream perfusion technology and have big facilities for batch operations. Moving to new facilities and training new staff is expensive, especially for products that are already in the market. Unless they were already planning to update their processes, it might not make financial sense for them to make these changes.

For instance, AstraZeneca is currently grappling with excess production capacity, making any alterations to its existing manufacturing infrastructure to accommodate continuous integrated bioprocessing financially unfeasible unless the economic benefits can offset both the capital expenses and the costs associated with underutilized existing infrastructure. Reportedly, AstraZeneca is working on establishing a semi-integrated continuous downstream manufacturing facility at a pilot scale, with considerations limited to transitioning the continuous capture step to a commercial scale.

Other challenges include a shortage of trained personnel and unidentified potential risks such as supply chain issues, difficulties with disposable technologies, and regulatory hurdles associated with deploying critical novel analytics required for continuous processes.

While there are challenges galore, if they are overcome, continuous manufacturing can offer game-changing advantages for the industry. Building small, modular, and flexible facilities that can easily adapt to production needs and run autonomously is a significant advantage. These facilities have the potential to eliminate the need to invest billions in large-scale manufacturing plants tailored to specific biologic drugs, even before completing clinical trials, which is the current industry norm.

This method has sizable potential in emerging economies like India due to several key factors. Firstly, individual patients in such countries face substantial out-of-pocket costs for healthcare, with out-of-pocket expenditures contributing to 43% of health expenditures in low-income countries compared to just 13% in high-income countries. Secondly, these nations are experiencing a disproportionate rise in chronic diseases among their populations. For instance, the incidence of diabetes has surged by 58% in Asia and 40% in Africa over the last decade, while Europe has seen a 2% decrease and unchanged in the United States.

These factors, coupled with population growth in emerging economies, have created rapidly expanding and highly price-sensitive markets for biotherapeutics in these regions. Given the limited presence of large-scale biologics manufacturing facilities in these countries, there exists a significant opportunity to establish integrated continuous bioprocessing plants capable of producing large volumes of biotherapeutic drugs at substantially reduced manufacturing costs. This approach could potentially address the healthcare affordability issues faced by patients in emerging economies like India, making essential biotherapeutic drugs more accessible and affordable.

“I don’t see the point of this work if it does not translate”, says Prof. Rathore. He is now working in collaboration with manufacturing companies to give his research a more pragmatic outlook.  He aims to integrate the continuous bioprocessing currently underway in his lab at IIT Delhi into practical supply chains through strategic collaborations with pharmaceutical companies. This can make biotherapeutics more affordable, accessible and feasible to patients who really need them to be.