Anthony Davies - President, Dark Horse Consulting, USA
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Joint plenary session: Regulatory updates and recent progress
Since 2007 Advanced Therapy Medicinal Products (ATMPs) are specifically regulated in the EU. So far, a limited number of ATMPs have been approved in the European Union despite considerable development activity in this field. As part of the Escher platform for regulatory innovation, Lygature, together with EFPIA, EBE and Utrecht University has carried out a project researching factors associated with success and failure in the development and commercialization of ATMP products in Europe.
The approval of first Advanced Therapy Medicinal Products (ATMPs) both in EU and US have raised high expectations towards novel cell- and gene-based medicinal products, especially for indications with high unmet medical needs. On the other hand, clinical trials of first CAR-T cell products have shown the difficulties related to the substantial genetic modification of T-cells in the form of severe adverse reactions, cytokine release syndrome (CRS) and neurotoxicity. It is well known that for cell-based products the product composition, quality and control of product variability are critical for safety and efficacy. For CAR-Ts certain signaling domains seem to be related to better cell persistence, whereas impact of the T-cell composition / characteristics on the product safety has not yet been clarified. For many cell-based products long in vitro culture has been associated with higher safety risks (e.g. tumourigenicity) and lower efficacy e.g. due to dedifferentiation or apoptosis of cells, leading to restrictions in cell expansion and lower cell doses. This presentation will discuss importance of early product design and how the balance between quality, safety and efficacy could be achieved.
Late Morning Session
Review of the exciting and diverse pipeline of cell and gene therapy projects within UCL with example case studies
Opportunities for project funding: internal, public funds, industry partners and university spin outs
Tackling the challenges of GMP manufacturing capability and capacity
Informa is looking for 5-6 CAT members and industry representatives to join a panel to address various concerns for those working in the clinical space for both cell and gene therapies – attendees will be able to submit questions in advance.
Points to be discussed include:
Early Afternoon Session
Informa is looking for 5 speakers to join this panel discussion looking at the below topics:
Restoring function of the central nervous system is a challenging task. The large cell replacement experience has offered promising results with different types of cells. Here we propose the adult brain cell auto transplantation as an attractive restoration alternative.
The strategy of autologous reimplantation was investigated in two monkey models:motor cortex lesion as a model of stroke and MPTP-treated monkeys as a parkinsonian model. Primocultures were obtained from cortical biopsy. Cells were grown in vitro as neuralcell ecosystem that consist in astrocytes and neural progenitors. In both models the cells survived and were migrated to the affected structures, respectively to the lesion area and the striatal structures. Significant functional recoveries were thus observed in both models.
Based on such preclinical result, a phase I-II clinical trial is planned for application inpatients affected by stroke.
Prior to that clinical trial, the cell production has to be performed in GMP conditions.For that purpose, and other applications in cell therapy, our public institution, the Lausanne University hospital, implemented a Cell Production Center (CPC) that is now accredited by Swissmedic (authorization n°507482). At the CPC an original concept with a module for production, Isocell Pro 1.8, was developed and qualified. This equipment concept allows to maintain a hermetically culture production in a class A environment by working in class D for operators.
As we all know, the way is long and costing from research to clinical applications. The Lausanne University hospital (CHUV) found a way to help teams of clinicians and researchers to approach that challenge in regenerative medicine
Ancillary materials (AM, also termed raw materials) are crucial for the quality, safety and efficacy of a cell or gene therapy product.
An increasing number of regulatory guidance documents helps to develop risk-mitigation strategies and qualification programs to select appropriate reagents.
The use of fully traceable, GMP manufactured and preferrably animal-derived component-free (ADCF) AM, significantly reduces qualification and validation efforts and helps to ensure consistency, safety and purity of cell & gene therapy medicinal products.
With the first approved cell and gene therapy medicines with significant market volume, the need of high quality AM is increasing strongly. Thus the AM suppliers have to maintain a high quality standard at significantly larger manufacturing scale.
In order to meet the growing demand for induced pluripotent stem cell (iPSC)-derived cells for research and therapeutic applications, we have systematically explored the application of traditional and novel cell culture technologies to increase the scale and automation of iPSC expansion, and both adherent and suspension iPSC differentiation. This presentation will summarize our lessons learned from commercializing different iPSC-derived research products and developing candidate therapeutic products.
In gene therapy manufacturing typical product-related impurities are vectors with deleted or rearranged DNA sequences. Empty particles can have lost their integrity and be prone to form aggregates and furthermore have impact on the immunogenicity profile when administered to patients. Transmission electron microscopy analysis of negatively stained AAV samples (nsTEM) is unmatched in providing detailed information of particle integrity. MiniTEM automatically images and quantifies the portion of broken capsids as well as process related impurities such as host cell debris. The MiniTEM analysis also provides the size distributions of the particles to give accurate data on sample purity.
Late Afternoon Session
Off the shelf ATMPs: from production to patient
Cryopreservation of cellular therapeutics: critical quality attributes
Storage and delivery on site
Case study: allogenic product of Bone Therapeutics
Informa is looking for 4 round-table leaders to host round-tables on the below topics: