Course overview:

• Pre-clinical Development (1h)
  • Historical overview of T cells products development. 
  • Challenges to be considered for translating a product from a research bench to clinical manufacturing.
  • Pre-clinical data package for regulatory submission.
  • Creating and Characterizing iPSC and iPSC-derived products.
  • Developing data to support the proposed use of Regenerative Medicine Products. 
  • Animal modeling – pre-clinical safety and efficacy.
  • Example of bench to bedside translation.
  • Understanding gene editing for pre-clinical development.

• IND Development (0.5h)
  • CTD/eCTD modular format and available opportunities for FDA interaction during IND development.
  • Components of the IND submission, the clinical research protocol and the related and required monitoring plans.
  • Components of the CMC and how to develop and present those components for inclusion in the IND.
  • Gathering of appropriate previous human and preclinical data to support the IND.
  • Working with GMP facility (Manufacturing and Quality) for tech transfer related to product manufacturing and release.

• Study Design, Conduct and Analysis of Clinical Trials (0.8h)
  • Confirmatory & Exploratory Analyses.
  • Choosing manufacture and product release criteria.
  • Biomarkers & Surrogate Endpoints.
  • Choosing the right trial endpoint.
  • Stopping rules.
  • Safety considerations.
  • Including replacements.
  • Addressing Missing Data in Clinical Trials.
  • Unique pediatric-specific considerations. 
  • Manual vs automated systems.
  • Fundamentals & advances in processing and manufacturing – the example of RBC reduction.

• Correlative Studies (0.4h)
  • Correlative studies in accurately assessing aspects such as Delivery and efficiency of gene transfer.
  • Target specificity.
  • Immunogenicity and toxicity – genotoxicity: insertional mutagenesis.
  • Long-term versus short-term expression.

• Cell Manufacturing (0.4h)
  • Principles of GMP as applied to manufacturing operations.
  • Therapeutic applications of cellular products.
  • Raw materials specifications and vendor selection.
  • Working with primary cells from patients and patient-specific product manufacturing.
  • Optimization of manufacturing environment.

• Manufacturing and Analytics of Viral Vectors (0.6h)
  • Basic differences between types of viral vectors, manufacturing methods, and applications.
  • Issues associated with the manufacturing of viral vector products, including scale and lot-to-lot variability.
  • Facilities and equipment needed to support GMP manufacturing.
  • Basic regulatory requirements governing the manufacture and release of viral vector products.
  • Value of adopting a risk-based approach in GMP manufacturing. 

• In Process and Release Testing (0.4h)
  • Principles of GMP as applied to testing; comparison of in-process and release testing. 
  • In-process testing and setting metrics for success.
  • Developing and qualifying appropriate release tests (compendial vs product specific).
  • Potency assays.

• Team Science/ Building Cross-Functional Teams (0.5h)
  • To understand how to create a multi-functional scientific team that addresses all of the requirements for creating, qualifying and delivering a cell therapy product to the clinic.
  • How to motivate and keep the team together during the lengthy translational stages of product development and when collaborating with industry partners.
  • Career development opportunities for cross-functional team members.

• Quality Assurance Development (0.5h)
  • Understanding what constitutes a Quality System. 
  • Understanding compliance requirements for cell therapy products.
  • Understanding the role Quality System plays in product development.
  • Developing Quality Systems appropriate to the stage of the project.

• Clinical Trial Case Studies: Deliver of Cell Therapy Products (0.6h)
  • Issues related to shipping cell and gene therapy products - Manufacturing Issue.
  • Issues related to the storage of cell and gene therapy products- Manufacturing Issue.
  • Issues related to infusing of cell and gene therapy products, including routes of administration and monitoring.
  • Define adverse event reporting structures: from clinical sites to sponsor and sponsor to FDA.
  • Approaching risk mitigation strategies after an unexpected adverse event. 
  • Nonconformities & deviations: communication & roles
  • Product release.

• Strategies for Regulatory Success; A Fireside Chat (0.4h)
  • The concept of holistic product development.
  • The importance of forward planning and thinking about how to make a product reproducibly.
  • The importance of early and continued discussions with the agency in reducing development time. 

• Evolving Financial Models for CAR-T and Gene Therapies (0.5h)
  • Understanding what goes into the actual cost of delivery of a clinical product.
  • Reimbursement.

• Protecting and Licensing Your Technology (0.6h)
  • To understand your options for engaging with industry to advance your technology and to fund additional research in your lab to develop new and useful technologies.
  • To understand intellectual property and strategies for protecting and maximizing value of your inventions.
  • To understand the licensing process for setting up robust relationships with the commercial partners.
  • To understand how technology you played a role in developing will be used and commercialized by industry.
  • To understand the potential scope of an academic/industry partnership revolving around gene and cell therapy technology (manufacturing, process development, assay development, quality improvement, technology transfer, research and development, etc.).

• Hot Topics and Controversies in Cell Therapy (0.6h)
  • Describe how insurance coverage practices can impact clinical outcomes in the setting of CAR T cell therapy.
  • Understand underutilization and disparities in access (in both trials and post-approval settings).
  • Discuss strategies to decrease regulatory burdens for onboarding.
  • Describe the potential (and challenges) of decentralized/”home brew” cellular therapy as one solution.