Biomanufacturing and Supply Chain Standardization Key to Success in Cell and Gene Therapy Industry Boom

The Wild West. Like changing the engine of a car while driving down the highway.

This was how several cell and gene therapy industry leaders characterized the field’s rapidly developing Biomanufacturing and supply chain environment at this year’s Maryland Tech Council (MTC) BIO Conference held in the BioHealth Capital Region (BHCR).

Cell and gene therapy is so new that its manufacturing and supply chain processes and best practices are still calcifying, leaving many organizations to learn on the fly as they attempt to build the efficiency and standardization necessary for the industry to truly take off.

Put simply, cell and gene therapy companies are doing something that’s basically never been done before. Only a handful of companies have successfully taken a cell and gene therapy product to market. Gene and cell therapy manufacturing and supply chain is truly a new frontier that is just starting to be explored and mapped.

Earlier this year at the Bio Innovation Conference during a panel entitled, “New Frontiers of Biomanufacturing,” had a vigorous discussion about the evolving state of cell and gene therapy manufacturing and innovation.  Panelists included  Vigene’s Chief Manufacturing Officer Jeffrey Hung, Ph.D.; Aaron Vernon, VP of Engineering and Supply Chain at Autolus; John Rowley, Ph.D., Founder, and Chief Product Officer at Rooster Bio; Chris McDonald, VP of Manufacturing at Kite Pharma and Robert Lindblad, Chief Medical Officer at Emmes Corporation, and was moderated by John Walker, Manufacturers Extension Liaison at NIIMBL (National Institute for Innovation in Manufacturing Biopharmaceuticals).

When asked, “What keeps you up at night?”, Jeffrey Hung of Vigene perfectly captured the conundrum facing those operating in the cell and gene therapy field: “What keeps me awake at night is the continued demand for clinical trial materials and commercial product while we keep having to innovate at a fast pace. It’s like trying to change a car’s engine while driving it down the highway. ”

Other panelists cited what seemed like inherent contradictions faced by a nascient cell and gene therapy industry. In essence, these companies are learning on the fly without an established set of rules to follow or even question. Production needs conflict with innovation; personalization is anathema to standardization; and being cutting edge often means they lack the tools, materials and the well-worn paths to regulatory approval already established in other biotech sectors.

“As a supporter of manufacturers…what we see is that everyone wants to innovate but at some point, you have to just bite the bullet and lock down your process to get reliable manufacturing techniques to move it along the regulatory pathway. Every tweak you do requires a lot of other work. You can work on innovation in the second stage of your product,” stated Robert Lindblad of Emmes.

“In the new frontier space, there are no reagents and no GMP reagents. You can’t source GMP reagents so you have to qualify reagents just for your product and your indication, which is not adequate to get a certificate of analysis from the FDA. As you are on the cutting edge, you don’t have the equipment to create a closed system, you don’t have the reagents you need to have GMP manufacturing, so you have to be creative and work with the agencies to get through the regulatory pathways to commercialization,” he added.

The personalized nature of cell and gene therapy also creates challenges for manufacturing standardization and supply chain. The one batch, one patient equation of autologous cell therapy makes it a unique and highly challenging manufacturing process.

“When you think about designing and building a plant you can’t build inventory. Biologic manufacturing allows for 2 or 3 years of inventory. For us, you can never take the plant down,” stated Chris McDonald of Kite Pharma. He added that in many ways building a cell therapy manufacturing plant is a lot easier than running one due to the challenges presented by personalization, constant production, lack of inventory and the overall newness of the industry.

Rooster Bio has built its business model around solving some of the field’s efficiency and standardization issues. Rooster is making great strides in its efforts to standardize parts of the manufacturing and supply chain processes by becoming the “Intel of cell banking.” By creating off-the-shelf, high-quality media and cells-similar in concept to what the Intel microchip did for the computer industry-Rooster hopes to help standardize an important segment of cell and gene therapy manufacturing process and supply chain, thereby increasing manufacturing efficiency while lowering the cost of cell and gene therapy costs to patients.

“One bad reagent going into a cell bank that’s supposed to last for a few years can be really debilitating. This is what makes the Rooster Bio business model possible. Innovation can’t happen without quality. On the innovation side we’re in the middle of the process of living cells transitioning from being just a tool for research into technology itself,” stated John Rowley of Rooster Bio.

He also cited Moore’s Law as an apt parallel for what’s currently developing in the cell and gene therapy field right now. Moore’s Law states that the capacity of microchips would likely double every year while computers would decrease in cost. Rowley drew a link between Moore’s Law, the rapid increase in monoclonal antibody manufacturing capacity and cost reductions of the 1990s and what is going on now in cell and gene therapy manufacturing and supply chain.

While improving the manufacturing and supply chain is critical, Aaron Vernon of Autolus reminded the audience of the real-world impact of cell and gene therapy development failure or success. He emphasized the need for stronger cell and gene therapy manufacturing and supply standardization because of the direct link between personalized therapies and impacts on individual patients.

“We have to have zero tolerance for manufacturing failures because of their direct impact on patients. There are a lot of moving parts and things get more complex over time. This doesn’t scale easily,” he stated. “We want to innovate all the time but we don’t decisions made early in the research process that hamper supply chain for a very long time.”

Because personalized medicine is tailored for specific patients-i.e. one batch, one patient-the stake, while always high in biotech manufacturing, are higher in cell and gene therapy manufacturing and supply chain.

This makes solving the industry’s manufacturing and supply chain questions even more pressing. Having more companies successfully commercialize their cell and gene therapy products and increased information sharing, even among competing companies, are critical to the industry’s future.

“There’s a huge amount of knowledge out there but there’s a ‘black box’ that only gives us information about what’s worked and what hasn’t really late in the game. We only learn from the FDA after the fact,” stated McDonald.

Instead of relying on the FDA, Walker wondered about the possibility of sharing successes and failures among cell and gene therapies competing for market share.

Walker offered the following thoughts to the panel, “Different companies know what’s working and what’s not but because of IP no one is sharing. As cell therapy is trying to move forward everyone is trying to protect their own space so they are not sharing failures. If you’re trying to move the field forward scientifically that’s one thing, but right now everyone is thinking commercially and everyone is in their silo, which is totally understandable”

Vernon noted that the Standards Coordinating Body and other organizations are working to develop manufacturing and supply chain standards for the industry and are actively seeking input from companies in the space.  

“What I’ve learned more than anything recently is that these organizations need more industry engagement. There are certain things-how we qualify shipping lanes, logistics, freezing, microbial testing, method validation-that are absolutely inefficient when we are reinventing the wheel all the time at different companies,” stated Vernon.

“Because this industry is so new-we only have 4 or 5 approved cell and gene therapy approved commercial products-it’s really just too early to be able to standardize,” added Hung.

Because it is in fact too early to standardize, cell and gene therapy organizations find themselves confronting a Catch-22. Manufacturing demand will compete with the need to innovate. The personalized nature of cell and gene therapy will be at odds with the push to standardize manufacturing and supply chain best practices. The push to beat the competition to market will inherently limit the data sharing necessary to uplift the entire industry.

While these manufacturing and supply challenges appear daunting, they always are when it comes to revolutionizing medicine. It’s the energy created by these contradictions that will drive progress and foment innovation; it’s the immense challenges of frontier industries like cell and gene therapy that will ensure the very best of the best rise to success to pave the way forward for the organizations that follow.  And it’s success that will breed more success, as the conflict between these seemingly opposing forces will only resolve itself over time as more companies take therapies to market and the stories of their struggles and successes become public knowledge.

It seems like the Wild West now but conquering new territory is always complex and messy. The car will eventually have time to slow down and get in the shop to fine-tune its engine, offering a smoother, more efficient and faster ride to its destination. 

The BHCR region’s burgeoning cell and gene therapy cluster, as represented by those on the “New Frontiers in Biomanfucturing” panel, will clearly play a leading role in fulfilling the promise of cell and gene therapies to deliver high-quality therapies and cures to patients in need while driving down costs over time. 

Learn more about working at Kite from Chris McDonald, VP of Manufacturing and Site Lead.