Cell and gene therapy must prioritize simplification, standardization before focusing on automation

Addressing the challenges that come with scaling up production to meet growth and demand

Cell and gene therapy has made incredible, rapid progress in recent years, with new treatments and cures emerging almost daily for previously untreatable diseases. However, as we work to bring these life-saving therapies to more patients, we must also address the challenges that come with scaling up production to meet the growth and demand of the industry. One major issue hindering progress is an over-reliance on automation for the sake of automation. This has led to complex systems and a host of pain points.

Traditional cell and gene therapy manufacturing processes suffer from shortages of specialized staff and frequently result in failures and delays. The root cause of these problems is the complexity of the processes and the number of interventions involved, which make it difficult to achieve consistency and reliability.

The solution is not automation, at least not as a first step. Rather, the solution is to simplify and streamline the process before automating it, which can save manufacturers seeking to scale from bench to bedside time, money and resources by minimizing manual handling, reducing the volume and quantity of machinery, and lowering the likelihood of contamination and batch failure.

The industry push toward automation has been driven by a desire to reduce the potential for human error and variability in the production process. While these are valid concerns, the industry has placed too much emphasis on automation without fully considering the downstream consequences.

It’s critical to remember these therapies are complex by nature, given that patient/donor cells comprise the drug product. Automation can add to that complexity by creating new challenges that paint groups into a corner and make it nearly impossible to flex the process for more efficiency. For example, when a novel insight is made about how to generate more potent cells, but a process is locked in by complex automation, it is nearly impossible to modify the protocol to incorporate the new strategy. A simplified process, by contrast, can incorporate new technology without starting over from scratch. By focusing first on simplification and standardization, such challenges can be mitigated and the automation process can be much more effective.

Prioritizing simplification and standardization

The only way to successfully scale cell and gene therapies is to prioritize simplicity, reproducibility and reliability in processes and products. This means prioritizing modular systems that communicate with one another efficiently and effectively and eliminating unnecessary complexity before turning to end-to-end automation. By doing so, it’s possible to streamline the workflow, reduce the number of non-value-added touchpoints, and save time, money and resources while improving patient outcomes. Simplicity is the key to cutting out waste, in terms of effort, raw materials and space.

Once workflows have been simplified, we can then coherently move toward standardization as an industry. Standardizing much of the workflow is a goal worth aspiring to, as it would dramatically speed up the period from research to clinical data and reduce the burden on the FDA. Standardization would allow reviewers to cross-check that a process and set of tools already approved in other INDs are being applied consistently. This can move the industry away from the current method of solving the same problems many times across different institutes and companies. For example, much of a chemistry, manufacturing and control (CMC) process can be standardized, with the specifics around dose, target and construct making up the proprietary “special sauce” unique to each clinical drug being developed.

Applying the 80/20 rule

One path to simplifying cell and gene therapy manufacturing is to apply the 80/20 rule, also known as the Pareto principle, which contends that 80% of the effects come from 20% of the causes. When applied to the cell and gene therapy industry, this principle can help manufacturers and researchers set priorities for the manufacturing processes most in need of standardization.

By identifying the 20% of manufacturing steps that have the most significant impact on the final product, researchers and manufacturers can standardize, streamline and optimize those steps to improve the efficiency and quality of the overall manufacturing process — all before adding automation to an already complex system. For example, 20% of cell and gene therapy approaches are likely responsible for 80% of the progress made in the field. By identifying these promising strategies, researchers and clinicians can focus their efforts on standardizing and advancing those processes to accelerate progress in the field.

Redefining automation

After simplifying and standardizing it becomes much more feasible to effectively move forward with automation. Doing so in a modular, simplified manner can create usable process building blocks common to streamlined and standardized workflows. This approach reduces the complexity of the automated system and makes the cost of automation substantially more manageable. Economies of scale come into focus with a smaller set of unit operations and interventions to automate.

At ScaleReady, eliminating the complexity that often comes with automation is one of our core aims. Our goal is to help cell and gene therapy manufacturers standardize and simplify their processes before automating what’s left to create a more streamlined, efficient production process.

We believe the success of the cell and gene therapy industry in the long term requires prioritization of simplicity and reliability across processes and products. This means challenging the desire to immediately and constantly automate everything. The cell and gene therapy industry can achieve successful economies of scale and bring these life-changing treatments to more patients around the world by combatting the preconceived notion that every step must be automated from the very beginning. There is a better way, a new way focused on simplicity that will deliver on the promise we all believe cell and gene therapies will achieve.

Josh Ludwig leads commercial operations as the global director for ScaleReady. He closely collaborates with ScaleReady’s EMEA commercial director, along with the rest of ScaleReady’s leadership team, to ensure ScaleReady addresses the longstanding industry need for a truly scalable and practical solution. Josh has more than a decade of experience in commercial leadership and business development in the medical device and cell and gene therapy industries with a specific focus on engaging directly with clients and achieving client and company goals.

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