By Patrick Thiaville, Ph.D., Thermo Fisher Scientific
The global demand for plasmid DNA has increased dramatically in recent years, fueled by a surge in the clinical development of next-generation cell and gene therapy products and more recently by the success of COVID-19 vaccines. Plasmid DNA (pDNA) provides the coding sequences needed to create viral vectors such as Adeno-associated virus (AAV) and Lentivirus (LV), DNA vaccines, CAR-T cell therapy, gene editing, cloning, mRNA vaccines, and personalized cell therapies.
Securing an adequate supply of GMP-quality pDNA to support the manufacturing needs of these advanced therapies is increasingly challenging. The number of suppliers with sufficient expertise and manufacturing capacity to deliver the volume of material needed to match clinical and commercial demand is limited. This can translate into supply chain bottlenecks, long wait times, and stalled R&D progress.
Another manufacturing concern is quality assurance, particularly within the context of the evolving regulatory landscape. Plasmid suppliers maintain their own manufacturing processes and their own approaches to quality and testing. While regulatory guidelines are trending more towards use of cGMP material earlier in the development process, there is still some ambiguity in the interpretation of the documents and a lack of global standardization. Hence companies may choose to implement a risk-based approach when developing their plasmid manufacturing strategy. To avoid late-stage changes and timeline disruptions associated with inconsistent levels of quality, the onus is on developers to establish procedures for evaluating the quality of their plasmids early in the development process. Doing so will help mitigate downstream risks and optimize clinical outcomes and patient safety.
This white paper provides insight into the market trends influencing the manufacture and supply of pDNA for advanced therapies and offers an in-depth discussion of the key challenges associated with transitioning from GMP-like to full cGMP quality. Guidance is also offered to address these challenges, including recommendations related to critical quality attributes, upstream processing, formulation and fill/finish, analytics, and flexible capacity planning.