New therapeutic modalities are challenging the biopharma industry as never before. The curative impact of first-wave chimeric antigen receptor (CAR)-T cell therapies in blood cancers, for example, has spurred dozens of companies to launch hundreds of clinical trials for next-generation advanced therapies.
However, a digital sea change is needed if we are to rapidly master the unique complexities for producing cell therapies at scale. Ori Biotech’s Chief Digital Officer Kevin Gordon discusses the key pain points that are preventing patients from accessing this new generation of curative therapies.
Shutterstock
Key insights:
● The industry is not currently meeting the needs of the majority of patients who most need access to advanced therapies.
● Centralised and paper-based processes are hampering manufacturing throughput and limiting scalability.
● Digital-first solutions offer a route towards smart, scalable, (where applicable) decentralised manufacturing.
Logistical challenges baked into CAR-T
Cell-based therapies have generated more excitement than perhaps any new modality since the start of the biotech revolution, demonstrating robust and durable cures for patients with fatal diseases who have often failed all other treatment options. Paving the way for this new era of personalised medicines are autologous CAR-T cell therapies. However, the clinical success of these therapies, coupled with expansion to earlier lines of treatment, has unfortunately left cell therapy makers as victims of their own scientific success – unable to produce enough therapeutic doses, with devastating consequences for untreated patients.
Established biopharmaceutical manufacturing methods do not scale for cell-based therapies. As a result, the industry has had to invest heavily in large manufacturing facilities and human operators in order to manufacture even a small number of products, bringing its own set of problems and bottlenecks.
Centralised Manufacturing approaches
Strictly centralised manufacturing approaches that make sense for large-batch small molecule or antibody production add complexity to personalised therapies derived from patient cells. Manufacturing advanced therapies in large facilities, often far away from hospitals, means that therapies often have to be shipped back and forth between the apheresis site and the manufacturing facility – regularly across countries or continents. Such centralised approaches will never be scalable and contribute to higher cost of goods and longer vein-to-vein times.
Paper-based processes
Cell therapy manufacturing is intricately tied to the existing paper-based manufacturing paradigm originally designed for large-batch antibody and small molecule manufacturing. For example, quality control for a single clinical dose of a cell therapy can require a 1,000-page paper batch record, a highly inefficient and costly method for tracking (and storing) data that does not let developers easily learn from or adapt processes.
Today, the same rigorous release process we apply to batches of small molecules or antibodies – which each produce thousands or millions of doses – must be applied to every single individual dose of an autologous cell therapy. The requirement for the quality team to manually review each individual paper batch record before a dose can be released to a patient adds huge amounts of time to the manufacturing process, a daunting bottleneck to producing cell therapies at scale.
Digital solutions can help solve these challenges at scale. Industry 4.0 offers a potential roadmap for improving advanced therapy manufacturing and alleviating the key obstacles that are holding back access to cell therapies.
Smart factories
A first step would be making the manufacturing technologies themselves smarter. Fully connected digital devices would also allow developers to capture information at every stage of manufacturing. This would help structure and aggregate data in a way that it is easily accessible for analysis, power faster optimisation, identify process efficiencies and eventually adapt mid-process to the needs of an individual patient’s cells. In cell and gene therapy manufacturing, a move towards smart factories – as used in other industries like automotive manufacturing – would implement IoT interconnectivity, helping detect instrumentation problems in real time, and preventing unnecessary batch failures.
Distributed manufacturing
Instead of cell and gene therapies being manufactured in one large central facility, production could take place in several smaller facilities located closer to treatment centres and their patients. This would reduce the logistical burden of shipping therapies back-and-forth and would reduce patient vein-to-vein waiting time. As manufacturing scales up, a digital-first approach would allow for a centralised quality control team to monitor all manufacturing processes taking place globally, in real time, via cloud computing, improving safety and efficiencies.
Across the industry, there is momentum building towards digitally native, decentralised processes. This urgency is based on more than just efficiency: in a time where demand for advanced therapies is only growing, digitalisation will give us a better understanding of the impact of individual manufacturing steps on therapeutic response, will open the door to more flexibility in tailoring therapies to individual patient needs, and will increase throughput to enhance accessibility for patients globally.
Digital approaches alone will not solve all the manufacturing challenges faced by advanced therapeutics manufacturers, but they will undoubtedly play a critical role as the industry strives to make these life-changing therapies available to all patients in need.