Evolving Challenges in Closed-System Biomanufacturing

Published on 13 November 2024

Navigating the Complexities of Closed-System Processing in Biomanufacturing: Key Challenges and the Need for Continuous Innovation

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Closed-system biomanufacturing has revolutionized cell and gene therapy production, offering unparalleled sterility and control. However, as the industry advances and regulatory expectations for contamination control increase, new challenges arise that demand innovative solutions. In this blog post, we’ll explore the evolving complexities of closed systems and discuss the need for continuous improvement in cell and gene therapy manufacturing.

The Importance of Sterility in Cell and Gene Therapy Manufacturing

Closed systems are critical in modern biomanufacturing, particularly for high-purity applications like cell and gene therapies. By minimizing exposure to environmental contaminants, these setups help manufacturers meet stringent regulatory demands and ensure sterility across production stages. Maintaining sterility within closed systems is paramount to ensure product quality and patient safety.

Challenges in Maintaining Sterility in Closed Systems

While closed systems offer significant advantages in sterility assurance, they also present unique challenges. One major hurdle is maintaining consistent sterility while integrating essential materials and components into the closed environment. Traditional methods, such as using multi-use bottles for media and supplements, can introduce contamination risks due to open manipulations and transfers. This necessitates the use of innovative solutions to ensure aseptic processing within closed systems.

1. Maintaining Consistent Sterility with Aseptic Connectors and Single-Use Components

A primary goal in closed-system biomanufacturing is to maintain sterility, yet integrating supplements like Human Serum Albumin (HSA) or other critical media without compromising the closed environment can be challenging. Traditional multi-use bottles require open transfers, which increase contamination risk. However, single-use bags with sterile, weldable tubing and aseptic connectors allow for sterile, contamination-free transfers, enabling materials to be added without disrupting the closed loop. For example, the Thermo Fisher HyPerforma™ Single-Use Bioreactor (S.U.B.) allows for the integration of single-use components that can add supplements like HSA aseptically, minimizing contamination risks and simplifying workflow in cell and gene therapy manufacturing.

Q: How do single-use technologies help maintain sterility in closed-system biomanufacturing?

A: Single-use bags with sterile weldable tubing and aseptic connectors allow contamination-free integration of materials, helping maintain sterility in closed systems.

The Role of Single-Use Technologies in Closed-System Biomanufacturing

Single-use technologies (SUT) play a crucial role in overcoming the challenges of closed-system biomanufacturing. By utilizing pre-sterilized, closed-system-compatible components, such as single-use bags, tubing assemblies, and connectors, manufacturers can minimize open manipulations and reduce contamination risks. SUT also streamlines workflows, improves efficiency, and facilitates scalability in cell and gene therapy manufacturing.

2. Workflow Efficiency vs. Process Complexity

Closed systems require optimized workflows to ensure efficiency, but integrating new materials and components without disrupting the controlled environment can increase process complexity. Every additional handling step, such as connecting or transferring supplements, requires careful planning to maintain sterility, adding to labor demands and operational costs. Single-use technology (SUT), such as pre-sterilized, weldable bags and connectors, reduces the need for intermediate steps, simplifying workflows without sacrificing quality. The Sartorius Flexsafe® Pro Mixer, for example, allows biomanufacturers to mix and integrate supplements in a closed, sterile environment, making it easier to maintain aseptic conditions and reduce complexity during media preparation for cell and gene therapy production.

3. Navigating Regulatory Compliance with Validated Components

Closed systems inherently support regulatory compliance in cell and gene therapy manufacturing by limiting contamination. However, as agencies increase expectations for contamination control, biomanufacturers must continually adapt their processes. Using validated, closed-system-compatible components, such as single-use bags with aseptic connectors, helps align processes with regulatory standards. Closed systems with single-use technologies and Restricted Access Barrier Systems (RABS) further support compliance by reducing contamination risks.

Q: Why is regulatory compliance easier with closed systems?

A: Closed systems with validated single-use components like aseptic connectors and RABS reduce contamination risks, aiding compliance with regulatory standards for cell and gene therapy manufacturing.

Scaling Up Closed-System Processes: Overcoming the Hurdles

4. Challenges in Scaling Closed Systems for High-Volume Production

Scaling a closed-system biomanufacturing process for cell and gene therapies adds unique complexities, particularly as high-volume production requires consistent sterility and contamination control across larger batches. Functionally closed systems using single-use components, such as barrier isolators and sterile weldable tubing, support large-scale production by maintaining sterility without sacrificing efficiency. These components allow biomanufacturers to scale processes effectively while upholding quality and regulatory compliance.

Q: Why is scaling challenging in closed-system biomanufacturing?

A: Scaling closed systems requires sterile, single-use components like sterile weldable tubing and barrier isolators to maintain sterility and consistency across large batches in cell and gene therapy production.

Addressing the Need for Continuous Innovation in Closed-System Biomanufacturing

For biomanufacturers already committed to closed systems for cell and gene therapy, the journey doesn’t end at implementation—it demands continuous adaptation and refinement. As regulations evolve and the need for efficiency and sterility grows, the demand for innovative, closed-system-compatible components like sterile weldable tubing, single-use bags, and validated aseptic connectors will only increase. Investing in these solutions can help biomanufacturers overcome the evolving challenges of closed systems, achieving greater safety, efficiency, and compliance.

Looking Forward: Stay Tuned for Solutions and Innovations

In our next post, “Innovative Solutions in Closed-System Biomanufacturing: Exploring the Tools and Technologies Driving Sterility and Efficiency,” we’ll dive into specific solutions available in the market, exploring how innovations in closed-system-compatible options can optimize biomanufacturing processes and elevate your operational capabilities.

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Next in the Series

“Innovative Solutions in Closed-System Biomanufacturing: Exploring the Tools and Technologies Driving Sterility and Efficiency” (Coming Soon)