CELL AND GENE THERAPY INSIGHTS

Preclinical and translational tools and strategies

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Preclinical and translational tools and strategies

Joined-up assays: defining best practices for an integrated approach to early-stage potency assay R&D, keeping the eventual goal of marketing application in mind
Use of organoids, tissues on-a-chip, and other emerging in vitro and in silico tools to support preclinical data packages and provide genuinely predictive clinical insights
- Standardization in the manufacture and usage of in vitro models
Biomarkers and surrogate marker development: regulatory acceptance criteria and implications for first-in-human trial designs
Computational biology and big data analytics tools for cell/gene therapy target identification/validation and non-clinical development
PK/PD modeling applied in the cell/gene therapy field Testing for immunotoxicity or genotoxicity: safety testing where in vivo models are unavailable
Addressing the lack of good non-clinical models for allogeneic cell therapy development
To what extent can we address long-term clinical efficacy through redosing of in vivo gene therapy products in preclinical models?

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Raw and starting materials

Guest Editor:

Gary du Moulin, Consultant in Quality Systems and Compliance Strategies at Massachusetts College of Pharmacy & Health Sciences

Regulatory agency expectations for raw and starting materials
- Qualification of raw materials
- Regulatory disharmony between different national and multinational jurisdictions
Evolving risk management considerations and best practices
- Long-term upstream supply chain strategies: anticipating and preparing for raw material and consumables shortages and challenges in obtaining starting materials related to COVID-19
Increasing consistency, scalability, and standardization - and reducing costs of raw materials
Analytical tool development to support material changes
Production of materials in-house vs outsourcing
Steps to removing a complex biological material from your process and replacing it
Control of starting materials for autologous and allogeneic cell therapies
- Cell line development upstream of allogeneic cell banking
- Cell sorting and selection for optimized manufacture

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Vector bioprocessing

Analysis of the rapidly evolving competitive landscape in vector manufacturing
- Viral vector capacity issues (AAV and LV)
- Future supply and demand trends in light of the current pandemic
Viral vector process intensification and streamlining production through automation and reduction in process steps
Production platforms
- Pros and cons of producer cell lines
Technological trends and advancements in vector purification
Shortfalls in the established bioanalytical toolkit
Viral clearance in viral vector processing
Reducing timeframes for process development activities and earlier process-related decision-making
How to protect your GMP vector production from COVID-19?
What does phase-appropriate GMP look like in practice?

Gene delivery/gene editing platform evolution

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Gene delivery/gene editing platform evolution

Gene editing platform/application evolution
- How and where are next-generation gene editing platforms being applied and with what benefit?
- Predicting future trends in gene editing platform evolution
Engineering/innovating around long-standing issues for AAV vectors as the field expands into larger patient populations
- Pre-existing immunity
- Redosing
- Enhancing specificity/tissue tropism: systemic delivery
- Improving AAV vector efficiency/potency to enable dose reduction and an improved toxicity profile?
Third-generation LV vectors in ex vivo and in vivo settings
- Have safety issues now been sufficiently addressed?
Non-viral delivery platforms: benefits, obstacles, and their potential future impact on the cell and gene therapy space mRNA delivery in the light of the approved COVID-19 vaccines
- Lipid nanoparticles
- Exosomes
- Electroporation

Industrializing immuno-oncology product manufacture and supply chain

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Industrializing immuno-oncology product manufacture and supply chain

Lessons learned during the second wave of approved CAR T cell therapies from the roll of out Kymriah and Yescarta.
- Improving cost effectiveness, with market and patient access in mind
- Difference between clinical and commercial CAR T cell therapy manufacturing
- What is the best approach to ensure such novel and personalized medicines find their patients – and the physicians who prescribe them?
Delivering cellular immunotherapy to larger patient groups
- Capacity and infrastructure requirements to enable widespread patient access
Supply chain improvements required by emerging cellular immunotherapy modalities (eg. TILs)
What will the cellular immunotherapy products we are manufacturing in 3–5 years’ time look like – and what does this means for today’s facility design?

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Global regulatory update

Guest Editor:

Alexis Cockroft, Regulatory Consultant at Lex Regulatory Ltd

National and global updates on novel and forthcoming guidance
Learnings from regulator knock-backs of BLAs/MAAs
Regulator perspectives on the evolving cell therapy and gene therapy CMC landscapes
Impact of the EMA’s ‘principles of GMP for manufacturing of starting materials of biological origin used to transfer genetic materials for the manufacture of ATMPs’
Managing different regulations in countries receiving centrally manufactured modified cell products and gene therapies
Expedited development pathways (eg. EU PRIME)
Regulations regarding combination products
Environmental Risk Assessment (ERA) for medicinal products containing/consisting of genetically modified organisms
Regulating unproven stem cell treatment/medical tourism
Disconnects between science and ethics

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New horizons in cellular immunotherapy

Impact on CoGs, product quality, and manufacturing cycle time and complexity of the range of cell engineering platform options
Emerging technologies to improve targeting of the tumor microenvironment and reduce toxicity issues
- Multiomics, single cell sequencing/analysis, non-invasive spatial imaging, novel in vitro cell/tissue models, computational biology and big data analysis, machine learning and AI
Next generation cellular immunotherapy modalities
T cell immunotherapies: what improvements are being made in enhancing safety, efficacy, and durability?
- Optimization approaches for allogeneic cell therapies
- Non-T-cell CARs (eg. NK-CARs, CAR macrophages)
- Optimization of tumor infiltrating lymphocyte autologous therapies
- Innovation in alternative cell therapy molecular design and multiplex cell engineering
How to approach antigen discovery in the solid tumor setting?
Current trends and future directions in combination therapy selection
How far away is in vivo gene immunotherapy?

Cell and gene therapy manufacturing scale-up/ scale-out

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Cell and gene therapy manufacturing scale-up/ scale-out

Guest Editor:

Nolan Sutherland, Senior Scientist at Ring Therapeutics

Increasing availability of ‘right-sized’, built-for-purpose cell and gene therapy bioprocessing technology on scale-up/-out approaches
Viral vector scale-up/scale-out: progress in scaling manufacturing platforms and boosting yields to enable the ongoing migration to larger indications
- Facilities designed for <2,000 L production capacities: challenges at large production scales
  - Safeguarding against over- and under-sizing vector manufacturing facilities
- Scale-up of adherent bioreactors
- Improving scalability of transient transfection processes
Exploring scalability-related pros and cons of emerging non-viral gene delivery platforms
Allogeneic cell therapy scale-up
Autologous cell therapy scale-out: centralized vs decentralized
Addressing the shortage in adequately trained/experienced personnel

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Gene therapy CMC and analytics

Guest Editor:

Anindya Dasgupta, Director of GMP at Expression

Improving the speed and cost-effectiveness of vector bioprocessing and the identification and measurement of quality attributes using cutting edge analytical tools
- PAT to accelerate bioprocess monitoring/testing
- Throughput-related issues
- Empty/full capsid ratio: assessing current tools and methodologies
- Next-generation sequencing in gene therapy product development and manufacture
- Measuring the impact of AAV vector engineering methods on the capsid and its transduction profile
- Standards and assay options for viral clearance and adventitious agent control in gene therapy manufacture
- Reducing the amount of final vector product required for QC and release testing
- In-process analytics and controls in the gene therapy field
CMC data required for an ultra-rare disease indication
- ‘Plug-and-play’ gene therapy platforms for ultra-rare indications
How is regulatory evolution reshaping the gene therapy CMC space?
- Changes in CMC guidance
- Potency assays

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Cell therapy bioprocessing

Guest Editor:

Alexey Bersenev, Director, Cell Therapy Processing & Advanced Cell Therapy Labs at Yale University School of Medicine

Cost of goods reduction and streamlining/simplifying manufacture
- Allogeneic cell therapy
- Reducing manufacturing process cycle times
- Managing the number and complexity of gene edits
- Industrializing manufacture of extracellular vesicle/exosome-based therapies
Automation and fully closed systems for cell therapy manufacturing
- CoGs analysis for closed/automated cell therapy bioprocessing tools
- Modular options to automate individual steps of the process
Cell differentiation approaches for cell therapy
Pros and cons of novel fill-finish platforms
Ensuring reduced timeframes for process development activities alongside earlier process-related decision-making
What does phase-appropriate GMP look like in practice?
Protecting GMP cell therapy manufacturing from COVID-19
- What will GMP manufacturing in the ’new normal’ look like?

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Tools of tomorrow

Cell & Gene Therapy Insights’ annual exploration of enabling tools andtherapeutic technology platforms likely to make a splash in 2023.