The future of biopharmaceutical production is shifting from centralized manufacturing to a decentralized model, bringing production closer to the point-of-care (POC). This approach is pivotal for efficiently delivering personalized medicines and addressing issues like drug shortages, supply chain challenges and equitable treatment access. Technological innovations, particularly in equipment, analytics, and quality control, are driving this transformation, enabling drug manufacturing at the POC in various settings, from local health centers to remote locations. The FDA and EMA are actively engaging with stakeholders to navigate the regulatory landscape and facilitate this shift. The FDA’s FRAME initiative and EMA’s focus groups are steps towards embracing portable and distributed manufacturing units for POC use.
Despite the promise, challenges remain, notably ensuring consistent quality across distributed sites. However, advances in digital technology, such as cloud-based systems, offer a way to standardize and connect quality systems, reducing risks and enhancing consistency. Additionally, machine learning (ML) is emerging as a tool to maintain product quality in manufacturing, with capabilities to detect process deviations in real time.
Decentralized manufacturing is particularly transformative for autologous cell and gene therapies (CGTs), which are inherently personalized, given that a patient’s own immune cells are transformed into precise tumor-targeting agents. The manufacturing process of CGTs is intricate and costly with logistical challenges due to the need for long-distance, cold-chain shipping of patient-specific materials. By shifting production to the point-of-care, these logistical hurdles can be significantly mitigated, enhancing the efficiency and feasibility of these groundbreaking treatments.
Industry leaders are pushing the boundaries to expedite and streamline CGT manufacturing. The current methods involve a patient’s T cells being modified in the lab to express a chimeric antigen receptor (CAR), which seeks out cancer cells. This labor-intensive process, taking up to several weeks, contributes to the high cost of therapies like Novartis’s Kymriah and Gilead Sciences’ Yescarta, along with newer entrants from Bristol Myers Squibb. The “vein-to-vein time,” or the duration from cell collection to re-infusion, is a crucial period that the sector is keen to shorten. Efforts to refine this process are underway. Robotics and automation are being heralded as the keys to scalability and efficiency, potentially enabling the setup of mini cell therapy factories even within local hospitals or treatment centers. This move toward automation aims to reduce the manual steps involved in manufacturing, thereby lowering costs and increasing accessibility, standardization and reducing human errors.
Orgenesis has made strides with its POCare Network, leveraging Orgenesis Mobile Processing and Lab Units (
OMPULs) to standardize CGT manufacturing. These units, essentially mobile mini-production facilities, are designed to replicate standardized processes across multiple sites, ensuring consistency and quality while allowing for flexibility to adapt to various modalities.
Expanding on this landscape,
OriBiotech has developed a proprietary platform aiming to revolutionize the way CGTs are produced. Their technology focuses on automating and standardizing the CGT manufacturing process, with the goal of increasing throughput, reducing production costs, and making therapies more accessible to patients. OriBiotech’s platform addresses one of the critical bottlenecks in CGT manufacturing—scalability—by providing a closed and automated system that can be implemented at local treatment centers, thus reducing the dependency on centralized manufacturing facilities.
Cellares is another key player in this emerging field, creating the
Cell Shuttle, a factory-in-a-box solution designed to automate CGT manufacturing. The Cell Shuttle aims to provide a scalable, end-to-end solution from cell processing to final formulation, facilitating the production of multiple therapies simultaneously. This approach not only has the potential to lower costs but also increases accessibility to life-saving treatments. By partnering with leading pharmaceutical companies and research institutions, Cellares is positioning its technology to become a cornerstone in the decentralized manufacturing of CGTs and itself as the first “Integrated Development and Manufacturing Organization”, and
IDMO.
Contract Manufacturing and Development Organization (CDMO) Lonza has developed the
Cocoon® Platform as an automated, closed system to allow POC cell therapy manufacturing in a decentralized setting.
The advent of technologies from companies like Orgenesis, OriBiotech, Lonza and Cellares is a testament to the industry’s commitment to overcoming the obstacles of CGT production. The standardization of processes and equipment through these innovative platforms is expected to streamline comparability testing, demonstrating that decentralized sites can reliably produce CGTs of consistent quality. Furthermore, the centralized oversight of quality assurance through cloud technology and periodic audits ensures that these decentralized units operate within the latest regulatory guidelines, adapting swiftly to new standards as they emerge.
In parallel, the evolution of autologous therapies is informing the development of allogeneic or “off-the-shelf” cell therapies. These treatments, derived from healthy donor cells, could be stored and ready for use, bypassing the need for two-way cell shipment. While they present new manufacturing and regulatory challenges, the pursuit of allogeneic therapies reflects the industry’s drive towards more practical and rapid treatment options.
The CGT sector’s progress in addressing manufacturing complexities not only accelerates therapy delivery but also enriches our understanding of managing treatment variability and demand. Streamlining processes like apheresis and cell processing could yield further time savings. As we bridge these manufacturing gaps, the seamless integration of supply chain elements stands as the next frontier in delivering advanced therapies more efficiently to those in need.
Decentralized manufacturing of CGTs is not just a theoretical concept but a practical solution being realized today. As the technology matures and regulatory frameworks adapt, this model could become the new standard for delivering personalized medical treatments, reshaping the landscape of healthcare and patient outcomes.
As the landscape for manufacturing cell and gene therapy products diversifies, with options ranging from in-house facilities spread across different locations to contract manufacturing organizations and even point-of-care production, the complexity of operational decisions escalates. This burgeoning matrix of possibilities necessitates a robust and intelligent orchestration layer. This digital conductor will be pivotal in determining the most suitable fulfillment pathway for each incoming treatment request from various treatment centers and hospitals.
This orchestration layer must leverage advanced analytics and real-time data to assess manufacturing capacities, proximity, patient needs, and logistical considerations. It will need to balance the urgency of treatment delivery with the practicalities and capacity of production and distribution, ensuring that each decision aligns with the overarching goal of delivering timely and effective patient care. The integration of such a system will be a cornerstone in the operational framework of CGT, providing a strategic, data-driven approach to manage the increasingly intricate web of manufacturing and treatment delivery. With the scaling of CGTs and artificial intelligence (AI) becoming a reality this orchestration will be supported and enabled by innovative AI capabilities for optimal resource utilization and user experience for the end-to-end delivery of personalized treatments.
In essence, the success of cell and gene therapy production will hinge not only on the innovations in manufacturing technology but equally on the sophistication of the systems that guide these therapies to their destination. The orchestration layer is not just an operational tool; it’s a strategic asset that will ensure agility, efficiency, and above all, patient-centricity in the CGT supply chain.
