CELL & GENE THERAPY INSIGHTS

SPOTlights 2022

  • Preclinical and translational tools and strategies

    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?

  • Raw and starting materials

    Raw and starting materials

    • 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

  • Vector bioprocessing

    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

    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 immunooncology product manufacture and supply chain

    Industrializing immunooncology 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?

  • Global regulatory update

    Global regulatory update

    • 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

  • New horizons in cellular immunotherapy

    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

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

    • 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

  • Gene therapy CMC and analytics

    Gene therapy CMC and analytics

    • 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

  • Cell therapy bioprocessing

    Cell therapy bioprocessing

    • 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?

  • Tools of tomorrow

    Tools of tomorrow

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