Gene Therapy Manufacturing: Scaling Up to Meet Growing Demand

In the rapidly evolving field of gene therapy, manufacturers are racing to scale up production to meet the increasing demand for treatments targeting larger patient populations. Recent developments in transfection technology are paving the way for more efficient and cost-effective manufacturing processes, potentially revolutionizing the industry's ability to produce gene therapies at scale.

The Challenge of Large-Scale Production

As gene therapy developers set their sights on polygenic indications with larger patient populations, such as Parkinson's disease, the need for increased manufacturing capacity has become paramount. While the industry has historically standardized around 200-liter bioreactors, higher dosing requirements and expanding patient populations are pushing demand towards 1,000-liter bioreactors and beyond.

Fletcher Malcom, Head of Strategy, Product and Business Development at Mirus Bio LLC, explains, "Most of the industry historically has standardized around 200-liter bioreactors, but higher dosing and larger patient populations are pushing manufacturing demand to 1,000+liter bioreactors. If developers can't find a cost-efficient way to scale up production, they risk undermining the commercial viability of their programs."

Overcoming the Transfection Complex Bottleneck

The primary challenge in scaling up gene therapy manufacturing lies in the stability of the transfection complex. Traditional methods require the preparation and addition of the transfection complex to the bioreactor within minutes to achieve optimal titers. This time-sensitive process becomes increasingly difficult as production scales up, with larger bioreactors requiring significantly more transfection complex to be delivered in the same short time frame.

This bottleneck has led to several issues in large-scale manufacturing:

1. Limits on scalability due to short delivery windows
2. Stressful work environments for employees managing complex deliveries
3. Increased variability in performance due to time constraints

Innovative Solutions for Stable Transfection

To address these challenges, companies like Mirus Bio are developing new technologies to enhance transfection complex stability. Mirus Bio's VirusGEN Stabilizer additive extends the stability of the transfection complex from 30 minutes to three hours, a six-fold improvement over standard methods.

"With the introduction of Mirus Bio's innovative VirusGEN Stabilizer additive, you can extend the stability of the transfection complex six-fold — from 30 minutes to three hours," Malcom states. "That means less scrambling to add the solution to your bioreactor, and more opportunities to scale up production into the thousands of liters."

In addition to improved stability, these new technologies also enable manufacturers to achieve higher titers and percentages of full capsids, increasing overall productivity. The ability to reduce transfection complex volume from 5% to 2% of culture volume further streamlines the manufacturing process, especially at larger scales.

These advancements offer several benefits to gene therapy manufacturers:

1. Productive manufacturing at scale while maintaining high productivity
2. Reduced risk due to more forgiving workflows
3. Better management of manufacturing costs through improved efficiency and reduced batch waste

As the gene therapy field continues to advance, these technological improvements in manufacturing processes will play a crucial role in bringing life-changing treatments to larger patient populations. By addressing key bottlenecks in production, the industry is poised to meet the growing demand for gene therapies and potentially revolutionize treatment options for millions of patients worldwide.