Potency Testing in Cell and Gene Therapy: A Deep Dive

Research Paper Overview:  Navigating the Complexities of Potency Testing in Cell and Gene Therapy Products

The research paper ‘Potency testing of cell and gene therapy products’ by Paula Salmikangas, Björn Carlsson, Christophe Klumb, Tatiana Reimer, and Steffen Thirstrup, delves into the complexities and significance of potency assessment in biological medicinal products, particularly in Cell and Gene Therapy Products (CGTs/ATMPs). Their collaboration highlights the challenges and methodologies associated with ensuring the therapeutic efficacy of these advanced biological medicines, bridging perspectives from the NDA Group in Sweden and the European Medicines Agency in the Netherlands.

 

 

Understanding Potency in Medical Products    

Potency, in the realm of medicinal products, defines their biological activity. Ideally, it should mirror the product’s Mechanism of Action (MoA) and align seamlessly with the clinical response. While various assay formats are available, for quick product releases, validated in vitro assays are pivotal. 

Complexities of Cell and Gene Therapy Products (CGTs)    

CGTs, also known as ATMPs, come with intricate compositions, encompassing elements like nucleic acids, viral vectors, and viable cells. This makes potency testing for them especially challenging. When cells undergo transduction with a viral vector, their potency isn’t just linked to the transgene expression. It also heavily depends on target cells and the efficiency of the transgene. 

International guidelines draw a clear picture of potency’s essence, linking it closely to the biological properties of the product. While animal-based in vivo models offer early insights into potency, in vitro assays have become indispensable for generating concrete, quantifiable outcomes. 

Regulatory Perspectives and Conclusions    

The paper highlights the regulatory differences between the European Union and the United States. The EU, under specific conditions, might lean towards surrogate assays, while the US FDA consistently demands a clear-cut quantitative functional potency assay for release. 

Potency assays are vital throughout the product development phase. They not only ensure the product’s quality at release and during storage but also track any alterations during production. Occasionally, non-clinical models might support these studies, especially when they mimic in vivo biological responses. 

Wrapping up, the path to crafting efficient potency assays for cell and gene therapies is filled with intricacies and time-sensitive challenges. With the ever-evolving landscape of cell and gene therapy products, particularly with the leaps in genome editing technologies, there’s an amplified demand for a meticulous approach to potency testing. The paper advocates for early consultations with regulatory authorities whenever there are hitches in potency testing. 

In summary, this research accentuates the need for early strategy development in potency testing to truly unlock the potential of cell and gene therapies. 

 

References:

Salmikangas, P., et.al. “Potency testing of cell and gene therapy products” Frontier (2023). https://doi.org/10.3389/fmed.2023.1190016

Article Authors:

Paula Salmikangas, Björn Carlsson, Christophe Klumb, Tatiana Reimer, and Steffen Thirstrup.