Can characterisation industrialise cell and gene therapy?  

The cell and gene therapy (CGT) market is rapidly expanding, and projections suggest it will reach over $90B by 2023. With a maturing clinical pipeline, many FDA-approved treatments are on the horizon. The biopharma industry must industrialise cell and gene therapy manufacturing to bring these life-saving therapies to a larger scale than ever before, says Dominic Clarke, CTO of Cell & Gene Therapies at Discovery Life Sciences. 

Challenges of cell and gene therapy manufacturing 

Compared to traditional biologics, CGTs are living drugs, making their development and manufacturing substantially more complex. Traditional molecular therapeutics have decades of standardised manufacturing practices, while CGT manufacturing has yet to reach this level of maturity. 

One uniquely challenging aspect of CGT manufacturing is the starting material. Both allogeneic and autologous cell therapies require initial intrinsically variable inputs, which may lead to therapeutic inconsistencies. Additionally, because of the speed at which CGT is advancing, innovation often outpaces regulatory guidance. This forces regulatory bodies to lean on the insights of industry experts but can create an inconsistent and difficult-to-navigate web of regulatory guidance.  

The steps to success 

Industrialising CGT requires consistent starting materials, comprehensive analytics, and systemic data integration. These steps will pave the way for reliable protocol standardisation to transform CGT manufacturing and production. 

In a broad sense, industrialising CGTs requires adopting a systemic Quality by Design (QbD) approach. The goal of a QbD approach is to identify Critical Quality Attributes (CQAs) of the process and to understand the attributes’ relationship with Critical Materials Attributes (CMAs) and Critical Process Parameters (CPAs). Essentially, QbD theory helps developers ensure that manufactured cells have the required therapeutic effect.  

In practice, the first key to CGT manufacturing and production is a consistent starting product. This requires CGT manufacturers to have a reliable and robustly characterised cell source—which must be profiled through comprehensive multi-omic analysis (i.e., genomics, transcriptomics, proteomics, metabolomics) to identify the critical determinants of success. 

Advanced analytics are also essential to validate and understand CGT quality. Integrating the key insights from donor characteristics through CGT performance will identify and establish the critical quality metrics defining robust production. Importantly, we need to eliminate information silos and integrate across teams and institutions to develop rigorous developmental protocols. Through strong data and documentation systems, we can create scalable and consistent CGT products to improve patient lives.  

What’s on the horizon? 

The potential of CGT in the clinic is staggering. Now, we must strategically design robust manufacturing and developmental standards to ensure more patients have access to these therapies. 

While CGT manufacturing has significant challenges, such as technically complex development and potentially variable starting materials, industry leaders can employ advanced analytical techniques to overcome these hurdles. Regulators, developers, and manufacturers must work together to establish appropriate guidelines, which requires collaboration across all elements of the value chain. By integrating our knowledge and employing rigorous quality systems from the outset, we can make the dream of precision medicine a mainstream reality.  


Dr Dominic Clarke is currently the Chief Technical Officer for CGT at Discovery Life Sciences and has held previous roles at HemaCare, Charles River Laboratories, Charter Medical and BioLife Solutions. Clarke currently serves as the Chair for the International Society for Cell and Gene Therapies Process Development & Manufacturing Committee. 

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