Advanced Therapies Europe took place from 9-12 September 2023 in Portugal. DDW’s Megan Thomas asked attendees: What is most important to scale from discovery to commercialisation of cell and gene therapies (CGTs)?
Joel Eichmann, Co-Founder, Green Elephant Biotech
It always comes down to time-to-market and risk minimisation. To cover these, it is critical to choose a manufacturing platform that allows linear scalability from lab scale to commercial scale. Especially for cell expansion, it should be avoided to change the growth environment by switching to another system when scaling up. This can lead to altered identity or yields, causing serious delays due to additional process development and characterisation at a late stage of product development.
Jeremy Roden, Vice President, Europe & Strategic Alliances, Phacilitate
The most critical factor in successfully scaling from discovery to commercialisation of a CGT, as emphasised by key opinion leaders at Advanced Therapies Europe, is a holistic focus on interoperability, early preparedness, and collaborative efforts.
Interoperability is the backbone of a seamless transition. Ensuring that all components of the therapy, from research and development to manufacturing and distribution, can effectively communicate and integrate is paramount. This streamlines the process, minimises errors, and maximises efficiency.
Early preparedness cannot be overstated. Rigorous planning and anticipating potential hurdles early on are fundamental. Adequate infrastructure, regulatory compliance, and resource allocation should be addressed from the outset. This proactive approach prevents costly delays and setbacks as the therapy advances towards commercialisation.
Collaboration is the linchpin for shared success. In the field of advanced therapies, it is rare for one single entity to manage ‘it all’ in isolation. Partnering with diverse stakeholders, from academia to industry, fosters innovation, shares expertise, and accelerates progress. Together, we can navigate the complex regulatory landscape, address manufacturing challenges, and ensure equitable patient access to these life-saving treatments.
In summary, when advancing from discovery to commercialisation in the realm of cell and gene therapy, it is the harmonious interplay of interoperability, early preparedness, and collaborative spirit that paves the way for transformative success.
Matthew Lakelin, VP Scientific Affairs and Product Development, TrakCel
The mantra that I would recommend for any developer of CGT products would be ‘begin with the end in mind’. The demands of commercial supply may seem a distant problem when CGT companies are planning first into human studies, but unnecessary complexities which are manageable for small-scale supply should be addressed as soon as possible, to ensure that only essential process steps are undertaken once the CGT product is supplied on a commercial basis.
CGT developers should be testing the mettle of various suppliers, supporting technologies and service providers during clinical development to ensure that these are appropriate and robust enough for commercial supply of the CGT product. Many of TrakCel’s customers will begin using orchestration software during early clinical development and produce an action plan for reaching the demands of commercial-scale supply, this plan will detail appropriate times in the development cycle where integrations can be introduced to the orchestration system (e.g., when to integrate their orchestration system with an MES, courier, payer approval system) in preparation for drug product marketing applications.
Jenny Stjernberg, Commercial Director, EMEA, ScaleReady
To successfully scale from discovery to commercialisation in the realm of CGTs, the primary focus should be on scaling up, out and having the ability to scale down again. This ensures flexibility to adapt to evolving research findings, regulatory requirements, and market demands. It allows for quick adjustments when unexpected challenges arise during development.
As you are starting to standardise your manufacturing process, it is important to early on, think about how it can be automated down the line. While it is tempting to automate processes for speed and efficiency, it’s crucial to understand your product and your process to automate the right unit operations, this prevents unnecessary complexities that can consume valuable time and resources, delaying the journey to commercialisation and restricting patient accessibility.
Furthermore, simplicity should precede automation. Streamlining processes and simplifying workflows before automation is essential. This simplification minimises the risk of scaling complexities and ensures that the foundation is solid before introducing automation.
While automation and speed are essential goals in CGT manufacturing, they should not overshadow the fundamental principles of flexibility, simplicity, and scalability. A successful transition from bench to bedside and boardroom hinges on a well-balanced approach that prioritises these key factors, ensuring efficient and effective commercialisation for the benefit of patients and the industry.
Stephen Sullivan, Chief Operating Officer, iPSirius
The most important thing to scale is realism. We need to work on therapeutic products that can be efficiently made by developed, validated, available, and cost-effective technologies. iPSirius has worked hard to simplify the manufacturing of its therapeutic product IPVAC1.0 to make it the simplest induced stem cell (iPS) cell product currently in development.
iPSirius is working with the Cell and Gene Therapy Catapult and the Scottish Blood Transfusion Service to manufacture IPVAC1.0. IPVAC1.0 uses iPS cells as a safe delivery system of cancer targets to prime a patient’s immune systems to better fight their cancer.
Dr Catherine Duchesneau, Senior Director of MS&T, RoslinCT
Scaling CGTs from discovery to commercialisation presents several formidable challenges. First and foremost is the need to scale up and scale out using an implementation of automated systems where possible, as early in development as possible. Many cell therapy processes, especially, are complex and require simplification and streamlining when moving through the phases to commercial manufacturing.
The other challenge revolves around analytics and ensuring that they are suitable and robust for the manufacturing process, ensuring the right product characteristics are captured and can be trended/quantified to ensure batch-to-batch consistency and efficiency. With that, a solid understanding of regulatory implications and quality must be maintained through every phase of the product lifecycle.
Effective technology transfer, whether internal or external, is a critical aspect of any scale-up and must be well thought out early and be executed with the right partners. Engaging with experts with a large breadth of knowledge in the CGT manufacturing space, including at a CDMO, provides invaluable knowledge on how to scale quickly and efficiently to commercial. Ideally, this engagement would happen early in discovery.
Dr Lindsay Davies, Chief Scientific Officer, NextCell Pharma
Translation from discovery to the clinic with CGTs presents challenges with respect to standardisation of production processes and critical quality attributes. One key focus in the development of our mesenchymal stromal cell (MSC) product development is to ensure that the drug can be accessible to patients irrespective of location. We envisage this as a true “off-the-shelf” product that can be used when needed, with no significant wait for the patient. For MSC therapies to be scalable for market and accessible to patients outside of specialist CGT centres, the product needs to be allogeneic, cryopreserved, and stable with a multi-year shelf-life. Cell formulation is also an essential consideration, ideally meaning fixed dosing of patients and direct bedside thawing with no post-processing steps or need for cleanrooms for formulation of the product. Simplicity is central to commercial scalability and reproducibility.
Of course, successful market establishment of such drug products extends beyond the product itself, rather representing a complex interweaving of medicine, finance, and regulations. For CGTs to successfully reach the market it is crucial to have an open and ongoing dialogue between the regulatory bodies, developers and health economists that extends through the whole development process, and beyond market authorisation.