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Gene therapies rely on plasmid DNA (pDNA). Consequently, continued growth in gene therapies is inseparable from continued growth in pDNA manufacturing. That growth seems assured. According to Grand View Research, the global pDNA manufacturing market currently has a value of $2.1 billion and will grow at a rate of 21.7% over the next seven years.

To make so much pDNA, developers depend on reliable sources of supplies. On March 30, 2023, Andrew Frazer, PhD, associate director scientific solutions, cell and gene therapy at Charles River Laboratories, explored the market and opportunities in a GEN webinar titled, “Advancements in Manufacturing for Rapid Delivery of Plasmid DNA Starting Materials.”

“The growing adoption and acceptance of advanced therapies utilizing pDNA—as a direct therapeutic product and as a critical starting material for manufacturing viral vectors, messenger RNA (mRNA), transient proteins, and other applications—is driving increased demand, which in turn creates some challenges as specialist pDNA manufacturers try to keep up with supply requirements,” Frazer explains. Indeed, the current high demand for plasmids can require booking manufacturing months in advance. Plus, insufficient supplies of pDNA cause expensive regulatory delays in therapeutic programs.

As Frazer explains: “Developers often need to navigate and manage a complex and fragmented supply chain with a high risk of disruption when you move toward regulatory approval for advanced therapy products.”

Ensuring quality and supply

The cost and quality of plasmids depends on grades and applications. Research-grade plasmids are used to perform in vitro R&D and preclinical studies. High quality (HQ)-grade plasmids can be used in clinical development. GMP-grade plasmids provide the highest quality (at the highest extensive regulatory requirements in a well controlled environment) and are required for clinical production. As Frazer adds, “There is an evolving quality landscape for pDNA and its use within advanced therapies.”

To address the supply challenges and provide customers with plasmids of the required grade, Charles River developed its eXpDNA™ plasmid manufacturing platform. It includes a plug-and-play toolbox that allows various levels of screening and quality control and helps reduce manufacturing risks, even for manufacturers that produce the challenging plasmids needed for advanced therapies. As an example, Frazer points out that plasmids containing long poly-A regions, which are common in advanced therapy applications, can be manufactured with “relatively little impact on the overall project cost and timelines.”

By standardizing the process, Charles River also resolves supply chain challenges. As Frazer explains, “our platform has allowed us to simplify our supply chain and hold larger stocks of materials, which effectively allows us to initiate projects immediately and avoid any issues related to long-lead-time consumables.”

In addition, Charles River provides complete analytics at any stage, from characterization through release testing.

Adding off-the-shelf plasmids

Manufacturing pDNA for a specific gene to create an advanced therapy requires custom manufacturing. “However, the other plasmids that are used routinely for different viral vector products offer an opportunity to standardize,” Frazer says.

Consequently, Charles River recently launched its off-the-shelf plasmid products. “This reduces the requirement for multiple repeat custom manufacturing of single plasmids,” Frazer says. “As a result, prices can be reduced and, importantly, customers have the opportunity to plan and place orders for these common plasmids on a gram versus batch basis, which helps avoid issues with under or overordering and wastage.”

With the eXpDNA™ plasmid platform and now off-the-shelf plasmids, Charles River seeks to resolve the key challenges in the pDNA market. Customers receive exactly the plasmids that they need—in the right amount, at the right quality, and on schedule. These plasmid manufacturing advancements can also permit savings in cost and time. As Frazer notes, these options “allow us to closely coordinate our manufacturing activities and improve overall project timelines.”


Charles River QR Code to bit.ly/3GzZzHR
Watch on-demand: Advancements in Manufacturing for Rapid Delivery of pDNA Starting Materials

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