Why Early Manufacturing Decisions in Cell & Gene Therapy Matter
By Erin Harris, Editor-In-Chief, Cell & Gene
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The cell and gene therapy sector is at a pivotal crossroads, where early manufacturing choices determine not only the timeline to clinic but the commercial future of life-changing products. During our recent Cell & Gene Live, Designing Early Manufacturing For Long-Term Success In CGT, expert panelists, Raymond Luke, Senior Director, MSAT at Verismo Therapeutics and Todd Luman, Executive Director, Process Sciences at Allogene, joined me to discuss practical guidance for organizations specializing in both autologous and allogeneic therapies.
Invest Early, Invest Wisely
We began our presentation by acknowledging the urgency many CGT companies feel to deliver new assets. However, both experts counseled a measured approach. “It’s very difficult in the cell and gene therapy space to make pivotal process changes due to comparability considerations,” Luman said. “So being thoughtful on where to make the right investment early on can pay extreme dividends later in the development cycle and time and costs.” From the outset, both panelists emphasized getting decisions right rather than fast by prioritizing long-term flexibility and robustness.
Luke echoed this theme, arguing for a strategic foundation. “Do not build in a lot of complexity from the start,” he said. “Building in a lot of complexity from an early phase perspective can be costly, time consuming, and can reduce future automation potential and scalability. Another thing that I always harp on is to collect as much data as possible. In order to make informed decisions about your product and process, you need to make sure that you understand it, and you cannot do that if you do not collect the data.”
Their advice resonates for any CGT company beginning process development with growth in mind.
Preparing for GMP and Tech Transfer
Transitioning from early engineering runs to GMP production requires forethought and empathy for those on the shop floor. Luke called attention to this operational challenge. “One of the most important things that many companies forget to do when it comes to ensuring that a tech transfer will be successful is to remember who the end user is. Oftentimes these processes and analytics are developed in process development labs staffed by scientists with PhDs and years of experience. But in the end, this will end up in clean rooms that are largely staffed by early career individuals who only have a couple of years of experience. Making sure that your process is robust enough is key, and simplicity really is key when you’re getting ready to tech transfer,” Luke said. The goal is to translate scientific complexity into user-friendly protocols that work reliably under commercial conditions.
Luman shared his own practical approach to tech transfer. “As we get closer to locking this process, start engaging the manufacturing folks and educating around the process. Ensure that you have that same equipment on the floor in manufacturing prior to execution and in process development and vet that equipment early on to see if it is going to be a roadblock or an opportunity to implement later. When you have a very good process description, work with the manufacturing staff to translate that into master batch records and pay close attention to the details. Don’t assume anything,” he said.
Downstream Decisions and Data Strategies
As the session progressed, Luman and Luke emphasized the downstream impact of upstream decisions whether related to scalability, product quality, or speed to market. “Oftentimes you want to adopt all-in-one devices, but that can trap you in what can be an inflexible platform,” Luke said. “When you don’t have enough product understanding yet, putting yourself in that space will make it difficult to evolve your process, adopt future innovations, and scale. If you don’t capture all the necessary data from your early manufacturing, you can’t later inform what kind of changes you want to make from a product quality and scalability perspective.” Both experts shared a clear message that the right data unlocks future innovation, while poor data habits can lock a company into expensive errors.
Luman expanded on this in the context of allogeneic therapies. “In allogeneic therapy, we focus on significant areas that cause variation to your drug product quality. That might be understanding donor variation, the genetic engineering components of your process, and the robustness of raw materials. Where you can invest early in method development, it’s indicative of your purported mechanism of action, and you’re going to have a lot of assays early on,” Luman said. Luke and Luman insisted that analytics must move from a checklist mentality to a real engine for understanding and improvement.
Practical Advice for Emerging Companies
For small and emerging CGT companies, data strategy is even more crucial. “You don’t get as many chances on goal here, so you want to get it right from the start,” Luman said. “Put into place a robust data structure and focus on the science of developing cell therapy, not coding, in the early stages.” Luke reinforced the importance of analytics. “Invest in your analytics early,” he advised. “The analytics that you base everything on are your release specs and those are the assays that are run. You’re going to miss a lot of information if you don’t capture all of the data available, so that later, when you’re looking at a potentially marketable therapeutic, you don’t have the information you could have gathered.”
Automation, Flexibility, and Preparing for What’s Next
The discussion closed with perspectives on automation and innovation. “Always do advanced analytics because you make understanding much simpler when you’re able to gather that data.” Luke said. “If you cannot do those analytics now, make sure there are samples and capabilities available to do them in the future.”
“We believe in allogeneic and the key there is access,” Luman said. “The whole field is really trying to create first, in paramount, efficacy and safety, but we want to build on accessibility and cost so every patient in need can receive efficacious therapeutics.”
Luke summarized the future of CAR-T and process excellence by sharing that next-generation therapies should deliver better safety profiles, improved efficacy, and lower cost. He explains that “it’s about process efficiencies,” automated robotic manufacturing and faster turnaround for analytics.
CGT manufacturing is not a sprint but a strategic marathon. Luke and Luman shared lessons that explain why simplicity, data discipline, and operational empathy are not just best practices but rather they are the foundation for scale, quality, and patient impact. Companies that act on these lessons will deliver better therapies, faster and at scale, for the patients who need them.
This is a summary of our detailed discussion. Tune into the full-length Cell & Gene Live for the nuance as well as the depth and breadth of our presentation.