Overcoming low cell viability and recovery efficiency through innovative isolation platforms and techniques is vital if cell therapies are to deliver on their considerable promise. In conjunction, innovations in cell expansion media and systems are critical to overcoming the technical and manufacturing challenges facing those developing cell and gene therapies. This spotlight will examine the latest developments in optimising cell yield and quality.
Guest Editor - Dr Nathalie Clement, University of Florida, USA
As cell and gene therapies move towards the clinic, critical developments in the production of viral vectors are required to enable large-scale manufacturing and distribution. A balanced overview of the merits and challenges of the different vector types (viral and non-viral) is provided; complemented by a discussion of the key manufacturing considerations to enable large-scale, quality-assured vectors for clinical use including culture systems and their impact on vector productivity:
- Critical issues for the scalable manufacture of AAV and Lentiviral vectors including process changes, drug product comparability, pre-clinical and clinical data requirements and the associated regulatory implications.
- Novel approaches to improve the vector yield using different cells, viruses and technology platforms.
- Balancing the need to drive down cost of goods with the challenge of creating stable cell lines for scaleable vector production.
- Latest advances in the development of non-viral vectors – implications for manufacturing and scalability.
Guest Editor: Dr Jean Stanton, J&J, USA
The cell and gene therapy industry is entering an exciting phase of accelerated growth, which carries many logistics challenges. Part 1 of the Supply Chain Management spotlight looks at the various hurdles and measures to overcome the complexities at the start of your supply chain including:
- Material challenges for cell and gene therapy products, qualification of raw and ancillary materials, harmonization of testing criteria and analytical tools and insight into the traceability of reagents.
- Cutting through the complexity and inconsistency in the language used to discuss the quality of raw materials required across the commercialization pathway.
- When should a company start to use GMP “level” materials; what are the implications for process development and cost of goods?
- Standardization across the industry - do we need it and can it be achieved?
Guest Editor: Dr Bruce Levine, UPenn, USA
With the key milestone of the recent approval of the first CAR-T therapy this is undoubtedly an exciting time for the field. Now more than ever it is essential to move the conversation forward in addressing the cost-effective, scaleable manufacture of these therapies, their safety and clinical outcomes, as well as the latest developments in replicating clinical success in solid tumors. This issue will examine:
- The latest developments in CAR-T translation and manufacturing including alternate gene transfer methods to deliver CARs; novel gene editing approaches, advances in CAR design to improve safety and efficacy, and progress in creating an ‘off-the-shelf’ allogeneic CAR-T therapy.
- The tool and technology requirements for scaleable CAR-T manufacture, with perspectives on vein-to-vein supply chain needs and a future outlook on critical process parameters and manufacturing bottlenecks.
- Clinical and manufacturing-related regulatory considerations, licensing and ethical considerations in the translation of CAR-T therapies.
Guest Editors: Dr Sven Kili, GSK & Dr Jaap Boelens, UMC Utrecht
The promising early clinical data from gene therapies for rare diseases has seen a resurgence in investment and optimism in the field. This spotlight will discuss the current clinical landscape as well as the critical considerations in moving these therapies towards successful commercialization:
- Navigating the transition from academia to early proof-of-concept studies and onto commercialization, including the selection of appropriate clinical end points.
- The latest clinical developments and outcomes of gene therapies for rare diseases of the CNS, metabolism, eye and liver.
- What can we learn from the commercial performance of these therapies thus far?
- What should the reimbursement price point be and how can companies establish a viable business strategy to support different payment models?
With the increased focus on cell and gene therapies as potentially curative therapies, critical developments in supply chain strategy are required to enable efficient and seamless delivery to patients. The second part of the Supply Chain Management series will address:
- Logistical considerations and challenges at the point of care, including package and shipping qualification, process qualification, storage equipment validation and storage infrastructure requirements.
- Novel approaches for end-to-end product tracking and management of data across the supply chain.
- Developments in Point of Care Manufacturing - can ‘GMP in a box’ be achieved for autologous therapies?
- Latest advances in cold chain technologies and cryopreservation – the potential impact of freeze-thawing cycles on product viability; PoC handling and training requirements.
Guest Editor: Dr Paula Salmikangas, NDA
As global regulatory agencies continue to evolve their policies to match the pace of development in cell and gene therapy, it’s essential for both academic and commercial scientists to understand the implications of these changes on their path to translation and product commercialization. This Spotlight provides the latest updates on:
- The impact of Japan’s innovative approach to regulating cell therapies and regenerative medicines not only within Japan but for international companies looking to collaborate/partner and take advantage of this regulatory environment.
- Recent success stories of commercial leaders in navigating their cell and gene therapy products through the regulatory landscape.
- Post-Brexit regulatory structure in the UK and what this means for your product.
- How the various regulatory agencies – FDA, EMA – are working to keep pace with this rapidly advancing field.
This spotlight will include discussions on the latest advances in bioprocessing to overcome the current bottlenecks in cell and gene therapy manufacture:
- Optimizing your cell culture and upstream processing as you move to commercial-scale manufacture - a review of the tools, technologies, methodologies, and platforms.
- Balancing the need to improve downstream processes to reduce CoGS with the advanced analytical requirements that enable product release and approval.
- Product and process requirements for successful upstream and downstream processing and approaches for process characterization, modelling and optimization.
- Latest advances in downstream technologies including harvesting, purification, enrichment, fill & finish to facilitate commercial-scale manufacture of vectors, plasmids and cell therapies.
Guest Editor - Dr Qasim Rafiq, University College London, UK
Advancing the discussions around this critical topic, the 3rd Annual Automation spotlight focuses on the latest developments including:
- Critical analysis of the different approaches to automation - balancing the need for flexibility with quality control and cost-effective scaleability with an indpeth look at the pros and cons of end-to-end automated manufacturing solutions vs integrated platforms.
- The latest advances in automation across various cell therapy manufacturing platforms and bioprocesses including cell culture and expansion, analytical and characterization tools, process monitoring and control.
- The key considerations when deciding to automate a complex biomanufacturing process such as autologous cell therapy manufacture, with in-depth discussion of the impact on cost of goods and risk management.
Guest Editor: Prof. Nik Willoughby, Heriot-Watt University, UK
This spotlight will examine the latest innovative solutions and critical issues around product scale-up and scale-out. Discussions will be centered around the following topics:
- Key cost drivers of scalability and measures to overcome comparability and scale-up challenges in cell therapy production.
- Process development technologies and facility design options for scale up of allogeneic cell therapies and approaches for GMP-compliant scale up platforms.
- Advances in microfluidic technologies for the scale up of cell and gene therapies.
- Manufacturing models and regulatory considerations for the scale out of autologous cell therapy products;
- Challenges in developing scale-out manufacturing processes.