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Cell and gene therapies are some of the most promising advances in modern medicine. With the first wave of personalized therapies already improving patient outcomes, dozens more are advancing through clinical trials. Several are nearing the final stages of FDA approval. The market is poised to grow at a double-digit compound annual growth rate of 36.52% over the next five years.
While cell and gene therapies are revolutionizing how we treat life-threatening diseases, they pose a number of significant manufacturing challenges. Conventional approaches to pharmaceutical manufacturing aren’t always feasible for the time-scale and customization required to produce personalized medicines.
In short, these new therapies require a new approach to the manufacturing process.
Tulip can help cell and gene therapy manufacturers operate with the agility these treatments demand.
By automating traceability, facilitating scale-up/out, and simplifying quality and compliance, Tulip can help you speed production at every stage.
Chapter One: Cell and Gene Therapies at a Glance
Gene and cell therapies are an emerging class of immunotherapy. These therapies work by engineering the genetic composition of a patient or donor’s white blood cells to fight rare cancers and neurological disorders, among other conditions.
At present, there are two methods for administering cell and gene therapies. Both require harvesting and modifying T-cells to produce chimeric antigen receptors (CARs). In essence, these modified T-cells use the body’s immune system to attach to tumors and reverse their progress.
The first two therapies to make it to market, Novartis’s Kymriah and Kite/Gilead’s Yescarta, are autologous CAR T therapies. With this method, T-cells are collected from a patient, modified, and then returned to the same patient. While these therapies enable truly personalized treatments, the inherently small batches (“batches of one”) and non-negotiable timelines (drugs must be completed while a patient is still treatable) make manufacturing them a challenge.
In contrast to the single patient served by autologous CAR T therapies, allogeneic CAR T therapies collect T-cells from donors to produce treatment for a larger population of patients. This form of one-to-many personalized therapy has the potential to reach more patients and can improve time-to-treatment by allowing firms to produce an inventory. Like autologous therapies, however, allogeneic treatments confront manufacturers with a number of unique challenges. These include tracing the potency, quality, and stability of each batch to ensure consistency across doses, and rapidly scaling production.
Chapter Two: Timing is Everything
Cell and gene products are inherently complicated to manufacture. But all of the difficulties are compounded by a single factor: time pressure. The breakneck pace of the firms bringing these therapies to market is matched only by the short and unforgiving development cycles needed to deliver treatments to patients. As a result, agility, flexibility, and data accessibility are essential to the manufacturing process.
Here are the challenges facing the firms that manufacture personalized medicines.
Speed – Development cycles in cell and gene therapy are extremely short. Each batch must be manufactured and administered to the patient in a matter of months. As a result, long “vein-to-vein” times can mean fewer patients reached or, worse, missing the window for treatment.
Highly manual – Manufacturing cell and gene therapies is manual and time-consuming. Strict regulatory standards for documentation and compliance lead to a heavy reliance on paper, which leads to longer cycle times, costly human effort, and higher incidences of notation or transcription error.
Scalability – The variability and customization characteristic of personalized medicine makes it difficult to scale between research, clinical, and market stages. Replicating benchtop results and transferring technology at scale is particularly challenging with biological materials, which can vary from patient to patient and donor to donor. To make matters more challenging, many therapies are developed along with academic protocols that weren’t designed for scale. As a result, scaling-up to meet demand and scaling out to new facilities comes with substantial risk.
Traceability – The “circular” progression of these therapies makes traceability essential. The motion from clinical settings for collection to GMP facilities for manufacturing and back involves multiple handoffs, and guaranteeing Chain of Custody and Chain of Identity is a must to ensure safe patient outcomes. With current methods, end-to-end traceability for every batch takes significant effort, and achieving the mandated level of traceability is a highly manual, time-consuming process.
Small batch sizes – Even with the shift toward allogeneic therapies, cell and gene therapies are produced in small batch sizes. Traditional manufacturing amortization schedules, which are based on large patient populations and long product life cycles, often don’t work for cell and gene therapies.
Need for real-time data – More than traditional pharmaceutical manufacturing processes, the materials necessary to produce cell and gene therapies are subject to variability. This is true from the design of viral vectors to maximizing purity and yield. As a result, the manufacture of cell and gene products can require ongoing process adjustments. Therefore it’s essential that manufacturers have real-time data to inform decisions and move quickly when necessary.
Lack of specialized software – A great deal of specialized hardware facilitates cell and gene therapy manufacturing. There’s been comparatively less innovation, however, in the realm of software. This means that cell and gene therapy firms are constrained to working with software solutions that were designed for a different manufacturing paradigm.
Chapter Three: How Tulip Can Help
In recognition of their potential to serve new patient populations, the FDA offers fast-track validation for cell and gene therapies. But to receive validation the FDA requires a software platform for managing and orchestrating the manufacturing process.
This is where Tulip can help.
Tulip is an application platform built for agile environments. Tulip provides all of the functionality you need to monitor and coordinate production in a GMP facility. And it does so in a way that rises to the speed, flexibility, and traceability required for personalized therapies.
Traditional production management solutions are slow to implement. The average roll-out takes 15-16 months. Waterfall-model deploys mean that late-breaking or changing requirements can push back timelines and delay time-to-value.
Further, these systems are hard to modify. Small customizations can take weeks to months. The costs add up.
With Tulip, manufacturers build applications and deploy them in days or weeks, not months. The platform is designed specifically to enable fast time to value in regulated environments. Tulip’s application builder lets you build multiple applications in parallel, deploy simultaneously, and iterate continuously. Applications can be modified, reconfigured, and scaled without harming other applications or upsetting validated processes. The result is increased flexibility, faster manufacturing cycles, and more visibility into processes.
We currently work with some of the top pharmaceutical manufacturers in the world. Our pharmaceutical customers use Tulip for tasks as diverse as equipment monitoring, digital history records, and as end-to-end production management and orchestration system for oral solid dose manufacturing. Tulip fits your production lines–not the other way around.
Here are some of the ways Tulip can help address the specific challenges of cell and gene therapy manufacturing.
Agile Deploys – Tulip provides the fastest time-to-value of enterprise manufacturing solutions. With Tulip, manufacturers can implement site-wide solutions using agile methodology–designing targeted, workable solutions fast and in parallel. This way you can introduce functionality and create value without spending months gathering requirements and designing a monolithic solution.
Native IoT to monitor processes – Tulip is an IIoT native platform. This means that Tulip can connect to your devices, sensors, and equipment out of the box. This reduces the amount of time spent manually collecting data and makes each of the data streams necessary for proving quality and compliance instantly available.
Real-time process visibility – Real-time analytics are an essential tool for minimizing lead times and ensuring quality. Tulip instruments your manufacturing processes, collecting data from equipment, machines, sensors, and operators automatically. All of the data collected by the platform is stored in easy-to-configure tables, and can be visualized in customizable analytics dashboards. This level of visibility typically exists beneath the level of validation and can help speed production by eliminating downtime and improving production routing processes.
Automated Traceability at the Patient Level – Ensuring traceability at the batch level takes a tremendous amount of manual effort. With Tulip, batch history and genealogy are automatically recorded and stored in searchable databases. Tulip apps can be used in production, in clinics, and at the point of care, as well as to coordinate logistics, making true end-to-end traceability possible.
Scalable, transferable software systems – One of the biggest challenges of traditional manufacturing systems is up to production and scaling out to CDMOs. Because software solutions are typically bespoke, each new facility requires a new solution, built from the ground up. Tulip applications scale up and -out seamlessly. Full production systems can be transferred to new facilities. New configurations can be completed in hours and days, not months. If you’re working with a CDMO, the applications you develop during the clinical stage can be rolled out to the new sites for the next phase.
Digital History Records – Traditional history records are manual, paper-based procedures. Tulip thinks about history records differently, making it easier than ever to access the parts of history records necessary for compliance.
Simplified Compliance – Simplified compliance is a natural result of better visibility, accessible data, and digital history records. Tulip collects all of the data and records you need to prove quality and compliance.
Chapter Four: Why Cell and Gene Therapy Manufacturers Trust Tulip
When it comes to cell and gene therapies, the interests of firms are closely aligned with those of patients. If simplifying manufacturing can secure a firm’s competitive advantage by speeding time to market, it can also ensure that more patients receive the lifesaving treatment they need.
But as cell and gene therapies push medicine forward, they push at the limits of traditional manufacturing systems.
Tulip offers a GMP-ready solution ready for the unique challenges of personalized medicine. Configurable for each stage of production, Tulip can help you bring your products to market faster and reduce the cost of doing so.
If you’re interested in how we can help simplify the way you manufacture personalized medicines, get in touch.
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