In contrast to traditional drug development, Cell and Gene Therapy (CGT) product development comes with a higher number of CMC challenges that often result in significant regulatory delays. Recent FDA guidance documents have recognised these obstacles, offering new insights into addressing some of the most prevalent CMC challenges. This presentation will discuss some of the most common CMC challenges in CGT in the context of applicable guidance and explore real-life case studies as examples, while underscoring the vital importance of proactive planning strategies for CGT sponsors.

The potency assay is a highly critical assay for cell and gene therapy products, and per the draft guidelines from FDA (2023), it is recommended to be included among the release tests already in Phase I clinical studies. The requirement of the potency assay is that it needs to reflect the main mechanism of action/s of the product which may not be fully known at an early development stage, and it should support potency assurance of the product. Using cellular function characterisation assays during the different phases of clinical development provides critical insights which help to establish the most relevant and appropriate potency assay for the specific product.

Developing potency assays and demonstrating that they measure appropriate biological activities has long been a significant challenge, particularly with the evolving regulatory landscape. But what if you are developing a pioneering new therapy with a multimodal mechanism-of-action? This presentation will showcase the challenges of developing a potency assay matrix for an engineered macrophage therapy and will consider how these assays support future commercial manufacturing strategies.

Cell therapy process development is costly and time-consuming. Implementation of quality-by-design principles can provide a structured approach; however, this can be hampered by a lack of relevant analytics. Characterisation of starting material, processes, and products is often limited to existing methods and can overlook critical measurements. Here we present a case study for allogeneic cell therapy that demonstrates the power of in-depth characterisation to drive decision-making.

Cell therapies are reaching late clinical phase and commercial-stage in high numbers, and the regulatory vacuum is being filled rapidly by agencies and pharmacopoeias with new guidelines and expectations. This presentation gives an overview of new global regulatory trends in the manufacturing and control space for cell therapies, and provides a high-level blueprint for developing such therapies, avoiding common pitfalls and enhancing compliance.

Development of iPSC-based therapies has been hampered by the challenge of navigating the complex regulatory pathway for these products. The presentation discusses how a robust manufacturing process with appropriate quality controls can be implemented to meet regulatory expectations at different stages. Regulatory requirements for donor tissue sourcing, quality control, and sequential banking approaches, as well as key aspects of product and process characterisation are addressed.

This presentation will cover the following topics: Characterisation vs. release assays (qualification vs validation), for information vs. release assays; when to use FIO and why, specification evolution during clinical development through to MAA and lastly, the need for adaptably of the quality parameters tested for release, as a function of the type of product under development and regulatory consideration.

Immatics’ TCR T based product candidates targeting PRAME are being evaluated for various solid tumors. The manufacturing process of these products has been developed at Immatics and has undergone multiple iterations for the purpose improving the TCR+ T cell quality and quantity. Manufacturing innovations including T cell enrichment led to improved product characteristics, manufacturing success rates, and reaching higher doses that may required to combat solid tumors. These favorable TCR-T product characteristics and high TCR-T levels in patients led to durable clinical responses in solid tumour indications in heavily pretreated patients. Immatics has aligned with FDA on patient population, trial design, CMC targeting registration-enabling Phase 3 trial in melanoma.

Industry must juggle business and scientific risks to thread the needle of successful C&GT drug product development. Key to this success is knowing why, when, and how to perform formal drug product comparability studies—and why, when, and how not to. This talk will provide road-tested and actionable feedback to guide sponsors when asking key questions related to navigating drug product comparability throughout the development lifecycle.

Legend BioTech will present their real-life experience, expanding their CAR-T production footprint world-wide in partnership with Johnson & Johnson. Topics to be presented include, construction of brown and green field GMP production facility, preclinical stage/start-up mentality, including GMP accreditation license, clinical phase with staggered ramp up and commercial phase with ramp up to steady state. 

Haematopoietic Stem Cell Gene Therapies are being developed to address a range of severe genetic diseases. However, manufacturing challenges have the potential to limit the applications of these therapies to a broader number of diseases. Here we present development on closing and automating the manufacturing process using state-of-the art equipment. Encouraging results were obtained, significantly reducing hands-on and overall processing time, and with comparable or improved product attributes.