December 2015 The rapidly advancing developments in gene editing have numerous implications and applications for the cell and gene therapy field – from disease modelling through to the potential editing of patient-derived cells to modify/correct disorders. The Gene Editing spotlight features a lead review from Prof. Andrew Bassett, Oxford University, UK discussing the main gene-editing technologies in detail: Zinc Fingers, TALENs and CRISPR-Cas9, comparing mechanisms of action, limitations and opportunities for future development and applications. Building upon this, we present a series of Expert Insight articles discussing potential clinical applications in more detail including: Cystic fibrosis Duchenne Muscular Dystrophy Genetic blood disorders and hemoglobinopathies Alongside the discussion of the incredible advances in gene editing applications, an ongoing patent dispute plays out in the media over the CRISPR-Cas9 technology. Dr Beatriz San Martin, Partner, FieldFisher, UK helps demystify and explain the IP situation and talks about the possible implications of the outcome of this dispute. We also hear from gene editing industry leaders, Sangamo BioSciences, as Dr Fyodor Urnov discusses their exciting progress towards the clinic with zinc finger nucleases in our exclusive podcast interview.
Supported by GE Healthcare Innovation and Excellence in ATMP Manufacturing PART 1: Defining Commercial Attributes Early in Product Development The sector has recently seen an influx of investment and interest from Big Pharma and VCs, in part due to the promising early clinical data from immunotherapies such as CAR T cells and engineered T cells. However, many questions and challenges remain on the path to successfully translating a cell-based therapy into a commercially viable product. Our expert Guest Editors – Prof. Peter Zandstra, University of Toronto; Dr Stephen Ward, Cell Therapy Catapult; and Dr Greg Russotti, Celgene Cellular Therapeutics – have identified the critical issues along the manufacturing pathway and these will be discussed across a 4-part Spotlight Series.
Supported by GE Healthcare Innovation and Excellence in ATMP Manufacturing PART 2: Integration of manufacturing and delivery into healthcare systems In Part One of our Cell & Gene Therapy Manufacturing Pathway spotlight series we focused on the early stages of product development, examining the key attributes that will eventually impact commercial viability. Here Part Two takes us on a step to evaluate potential solutions to the core manufacturing and logistical challenges involved in cost-effectively delivering cell and gene therapies to patients. Working with our expert Guest Editors – Dr Gregory Russotti (Celgene Cellular Therapeutics, USA), Dr Stephen Ward (Cell Therapy Catapult, UK), and Dr Peter Zandstra (Univ. Toronto, Canada) – we have selected world-leading authors from multiple stakeholder groups: academic centers, translational institutions, cell and gene therapy manufacturers, and equipment and service providers; all of whom are invested in progressing the translation of this promising new technology.
GUEST EDITORS Dr Mahendra Rao, Founder and CSO at Mahendra Rao LLC, USA and Prof. Jun Takahashi, Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan. The discovery of pluripotent stem cells and their capacity for cell-type-specific differentiation have revolutionized our approach to cell therapy. This spotlight showcases the latest clinical advances in utilizing pluripotent cells and discusses potential solutions to the core challenges related to their manufacture, distribution and delivery.
Supported by GE Healthcare Innovation and Excellence in ATMP Manufacturing PART 3: Understanding your product and processes Guest editors: Greg Russotti, Stephen Ward & Peter Zandstra As more cell and gene therapies move towards the clinic, manufacturers are faced with a number of challenges pertaining to the move from clinical-stage bioprocesing to commercial-scale manufacturing. What are the implications of making process changes as you move towards commercialization and how can you control for these variables and the potential risks they introduce? This spotlight addresses these critical questions including.
GUEST EDITOR Dr Qasim Rafiq, Assistant Professor in Bioprocess Engineering at Aston University, UK This Spotlight focuses on answering the key questions facing those grappling with how to use automation in the production of their cell and gene therapy candidates. At what stage in process development should I first consider automated single-use systems? What impact can I expect automation to have on cost, quality and reproducibility?
GUEST EDITOR Prof. Axel Schambach, Hannover Medical School, Germany 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 viral vector types 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.
Supported by GE Healthcare Innovation and Excellence in ATMP Manufacturing PART 4: Latest advances in the analytical toolkit GUEST EDITORS: Greg Russotti, Stephen Ward & Peter Zandstra The move towards commercialization of cell and gene therapies invariably requires changes and modifications across multiple steps in the clinical-stage manufacturing pathway, in particular with the increasing need to move from manual to closed-system and automated processes. It is critical then that a manufacturer is equipped with the analytical tools to enable product comparability, quality control and de-risking the process changes inherent in moving to commercial scale manufacturing.
February 2017 GUEST EDITOR Prof. George M Church, Professor of Genetics at Harvard Medical School, USA The rapidly advancing developments in gene editing have numerous implications and applications for the cell and gene therapy field – from disease modelling through to the potential editing of patient-derived cells to modify/correct disorders. The Gene Editing spotlight will feature updates from leading groups who are focused on utilizing gene editing technologies to advance cell and gene therapeutic approaches.
As the cell and gene therapy sector matures, the requirement for robust and high quality supply of GMP-compliant raw and ancillary materials becomes more and more of an imperative. This spotlight looks at the key current issues with a focus on real-world experiences: Donor screening and selection Optimizing raw materials at source: key considerations for the safe collection and processing of cell source material Characterization of raw materials: identity, purity and functionality testing Understanding the regulatory requirements
Guest Editor - Dr Richard Harbottle As cell and gene therapies move towards the clinic, critical developments in the production of alternatives to viral vectors are required to enable large-scale manufacturing and distribution. A overview of the latest developments in the design and advantages of next generation vectors will be provided, complemented by a discussion of the key manufacturing considerations to enable large-scale, quality-assured vectors for clinical use.
Guest Editor - Dr Isabelle Riviere The promising clinical results achieved in cancer patients treated with CAR-T cells has provided optimism and subsequent investment in the development of this technology. As we move towards the clinic, it is essential that reproducible manufacturing processes that generate high-quality, clinical-grade CAR-T cell products are developed and refined. This Spotlight discusses the challenges faced across the CAR-T manufacturing pathway, including standardization, automation, quality control, scaleability to meet patient demand, as well as the state of the art manufacturing platforms.
Examining the latest developments and thinking in preservation and packaging for cell and gene therapies, this spotlight looks at: The latest advances in cryopreservation technology Biopreservation Best Practices for regenerative medicine GMP manufacturing & focus on optimized biopreservation media When is the best time to start identifying your biopreservation and symbiotic supply chain strategy, and how to ensure a positive impact on Cost of Goods? Future goals, including alternative approaches to preservation without cryopreservation
Guest Editor - Dr Joanne Kurtzberg This timely spotlight brings you the latest advances and developments in cord blood manufacturing and clinical development. In collaboration with world renowned expert Dr Joanne Kurtzberg, this spotlight includes a selection of content from leading opinion leaders: Emerging use of cord blood in Regenerative medicine Advances in cord blood manufacturing Clinical translation of cord blood Use of cord blood in pediatric inherited metabolic diseases – update on clinical developments Unrelated cord blood transplantation in non malignant and malignant diseases Economics of cord blood banking
Ever more cell and gene therapies are entering clinical development, amplifying the requirement for novel purification systems designed specifically to meet regulatory requirements whilst increasing yield. This spotlight will provide a forum for discussing the current challenges and latest developments in delivering high purity cells and vectors including Harvesting, Purification, Enrichment and Fill-Finish strategies.
Guest Editor - Dr Qasim Rafiq, University College London, UK Our 2nd annual automation spotlight focuses on tackling the key questions facing those grappling with how to use automation, disposables and single-use technologies in the production of their cell and gene therapy candidates. The issue includes discussions on the: Question of when and what to automate Emerging business models for automation Potential benefits of automation for the production of cell therapies Application of automation in process monitoring and control in cell therapy manufacture Progress and Prospects of automation in CAR T manufacturing
Efficient and effective scale-up of production for viral vectors and allogeneic cell therapies and scale-out of production for autologous cell therapies; everyone agrees that these are absolutely key to the development of commercially viable products. But how can CoGs be controlled in practice? And what’s the optimal timing to start working on scale-up or scale-out? This spotlight includes the latest thinking from those leading the field, to help you define the right strategy for your product.
From the point of collection through to point of care delivery of advanced therapies to patients, there are myriad challenges that must be overcome to enable product commercialization. From sourcing clinical grade cells/tissue, training requirements through cost implications to regulatory compliance, this spotlight discusses in detail pressing issues such as: Key practical considerations across the whole supply chain - from vein-to-vein - including the procurement and handling of your soure material to ensure quality, safety and compliance with regulatory requirements Storage infrastructure requirements at Point of Care: Are we suitably geared up for cell and gene therapies becoming routine clinical practice The impact of different thawing techniques on quality and viability of cell and gene products What are the implications of the current regulatory guidance on PoC handling, storage and thawing? End to end tracking of your product; in-flight monitoring of product to ensure quality at the bed side Big data management across the supply chain Utilizing advanced, cloud-ready software systems to effectively and efficiently manage data
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.
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 addresses: 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. How the various regulatory agencies – FDA, EMA – are working to keep pace with this rapidly advancing field.
Guest Editors: Dr Sven Kili, Sven Kili Consulting Ltd & Dr Jaap Boelens, Memorial Sloan Kettering Cancer Center The promising early clinical data from gene therapies for rare diseases has seen a resurgence in investment and optimism in the field. This spotlight discusses the current clinical landscape as well as the critical considerations in moving these therapies towards successful commercialization.
Adeno-associated viral vectors (AAV) have shown great promise for sustained expression of a therapeutic gene in vivo. Obstacles remain however for gene therapy to broaden its impact beyond niche indications; currently clinically considered AAVs are repurposed naturally occurring viral entities that bring with them limitations imposed by its viral biology. For example, AAV is endemic in humans which results in a large proportion of patients harboring memory responses to AAV antigens, preventing them from benefiting from a future AAV gene therapy. Efforts therefore have turned to building novel synthetic AAV-based gene transfer vehicles that diverge sufficiently from their natural peers, such as the Anc-80 AAV vector. This spotlight, in partnership with Lonza, provides insight into the development and manufacture of a novel synthetic viral vector: Anc-80 AAV, with a collection of peer-reviewed articles and interviews with leading experts.
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: Dr Jan Thirkettle, Chief Development Officer, Freeline Therapeutics Building upon the February 2018 Spotlight on Viral and Non-Viral Vector Manufacturing, this series of interviews, articles and webinars will provide an update on the latest developments in optimizing vector and plasmid manufacturing. Hear from key opinion leaders on the cutting-edge scientific approaches being developed in efforts to refine vector performance, as well as advances in technology platforms to streamline and improve efficiencies in the manufacture of these crucial approaches.
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.
Guest Editor: Greg Russotti, Vice President, Technical Operations, Celgene Cellular Therapeutics
A perennially challenging area for cell therapy, product characterization/CMC has lately come to the fore as perhaps THE next critical manufacturing-related obstacle that must be properly addressed. Heavily funded consortia and renewed investment (from established tool providers and new faces on the cell therapy scene alike) are helping to drive technological innovation, regulatory guideline development and standardization efforts. But fundamental questions remain: which assays and solutions do you really need to employ? Whose product characterization standards should you meet? And what is the most cost-effective way to strengthen and accelerate Quality Control processes for novel cell therapies approaching commercialization?
- Recent evolution in product characterization tools (eg. flow cytometry, live cell imaging, single cell analysis)
- How to reduce the heavy burden of QC and release testing on production timelines and Cost of Goods?
- How are regulators’ expectations and requirements evolving as cell therapies continue to advance into the commercial sphere – for instance, in regard to potency and comparability?
- What is the state-of-the-art – and practical utility of – in-process analytics today?
- Troubleshooting apheresis and leukapheresis processes and management
- Interrogating the predictability of raw and starting materials to inform subsequent bioprocessing
- Regulatory compliance and standardization
- Next-generation raw materials (serum-free media)
- Towards stable vector production platforms
- Relative pros and cons of the latest automated upstream bioprocessing unit operations and all-in-one devices
- Insights into scale-up success factors
GUEST EDITOR: Professor R. Jude Samulski, University of North Carolina at Chapel Hill
The landmark approval of Spark Therapeutics’ Luxturna changed the landscape of gene therapy forever and brought many lingering and emerging issues into sharp relief – not least, the need for viral and non-viral vector manufacturing to advance to a stage where it is genuinely fit for commercial purpose. As the current capacity crunch intensifies, the onus is on efficiency in product development and manufacture as never before.
- Advances in gene therapy characterization and QC
- Keys to successfully validating vector bioprocesses
- Latest regulatory guidance
- Assessing the latest strategic and technical solutions for autologous cellular immunotherapy product development and scalable manufacture (including automation technology)
- Next-generation CAR-T platforms, TCRs & combination approaches and enabling technologies
- Focus on the convergence of immuno-oncology and gene editing
- Progressing allogeneic cancer immunotherapy
GUEST EDITOR: Dr Christiane Niederlaender, Senior Quality Assessor, Biologicals, MHRA
The past few years have witnessed an unprecedented increase in the range of expedited regulatory pathways potentially available to cell & gene therapy developers across the world. From RMAT to PRIME, and from Breakthrough Designation to the PMD Act, a weight of experience and insight now exists to help you capitalize on the benefits whilst avoiding the pitfalls.
- Strategic pros/cons and practical considerations with accelerated development and conditional approval pathways
- Keys to remaining nimble and flexible with clinical trial designs and parallel product/process development
- Step-by-step guides to making successful pathway applications
- Current and likely future preclinical requirements for established and emerging cell & gene therapy modalities
- Accelerating toxicology studies
- Addressing the need for predictive tools in immunotherapy
GUEST EDITOR: Lee Buckler, President & CEO, RepliCel Life Sciences Inc
Recent product approvals have only increased the sense of urgency to find viable pricing and reimbursement models for cell & gene therapies. They have also brought into sharper focus the need to educate and work with a wide variety of healthcare sector stakeholders – and of course, patients themselves - to ensure society benefits fully from such novel, disruptive therapeutic technologies.
- Evaluating the suitability of evolving P+R models
- Dissecting the market and patient access approaches of cell & gene therapy sector leaders
- Multiple stakeholder engagement strategies
- Product purification and polishing (of both cell-based therapies and viral vectors)
- Fill & finish and preparation for biopreservation
- Release testing
- Making the business case for decentralized manufacturing
- The role of automation in enabling local and point of care bioprocessing
- Defining fit-for-purpose regulatory compliance models
GUEST EDITOR: Dr Timothy Miller, President & CEO, Abeona Therapeutics
The dramatic recent growth of a dedicated clinical tools and services sector signals both the rapid maturation of the advanced therapies space, and a growing awareness that specific, fit-for-purpose clinical trial protocols are needed to cater for the nuances of this field with its widely varying component technology platforms and target indications.
- Clinical trial protocols to prepare patients for in vivo and ex vivo gene therapy
- Blueprints for clinical operations and patient recruitment success
- Utility of adaptive trial designs in cell & gene therapy
GUEST EDITOR: TBA
Exploring the promise of synthetic biology in the cancer immunotherapy space in particular, this special edition will focus on enabling technologies at the bleeding edge with the potential to boost both safety and efficacy.
- Gene editing
- On/off switches to control T cell activation
With 2019 set to break yet more new ground in terms of commercial advances, translational and clinical R&D progress and platform technology innovation, the Twenty-Tens will surely go down as the most significant decade to date for the cell & gene therapy field. This month, CGTI reviews and celebrates remarkable recent progress, and previews a new year and decade through analysis of 2019’s major trends and talking points – what will the Twenties hold in store for cell & gene therapy?
- KOL insights, reflections and horizon-gazing – just how far have we come and where do we go next?
- What were the most significant advances and issues of 2019 in terms of providing pointers to the future?
- Identifying both the key short-, mid- and longer-term challenges facing the global cell & gene therapy sector and next steps to their resolution. (Commercialisation, finance, manufacturing, R&D, regulation)
- Geographical analysis – how is the world of cell & gene therapy likely to evolve?
COMING IN DECEMBER 2019
Welcome to the Cell and Gene Therapy Insights Spotlights - helping address the critical issues facing those in the field through peer reviewed content, interactive multimedia, interviews, webinars and more.