Continuous Bioprocessing: Advancing Biomanufacturing Through Process Intensification

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Traditional batch bioprocessing involves growing and processing cells in isolated batches over defined periods of time. While effective, batch processing is inefficient and costly. Continuous bioprocessing aims to address these challenges through process intensification. It enables non-stop manufacturing by maintaining cells in a constant growth state through immobilization or perfusion. Key components like media, air, and harvested product continuously flow in and out of the bioreactor. This allows round-the-clock production at small footprint and high yields.

Moving From Batch To Continuous Operations

Adopting a continuous approach requires fundamental changes in processing strategy and equipment design. In batch mode, each step from inoculation to harvest is performed sequentially in the same vessel. Continuous processes separate these unit operations across optimized specialized equipment. For example, cell expansion may occur in a series of stirred-tank bioreactors Daughter vessels then seed cell propagation in airlift or fluidized bed bioreactors optimized for high density growth. Separate downstream ...
... units continuously harvest and purify products. Precise process control is key to maintaining stable physiological conditions for high performing cell lines.

Enabling Technologies For Continuous Processing

Establishing a true continuous workflow demands novel bioreactor configurations like perfusion and fixed-bed reactors. Perfusion systems offer higher cell densities by retaining viable cells inside while spent media flows out. Fixed-bed bioreactors like fluidized beds immobilize cells on microcarriers to achieve high density growth. They continuous bioprocessing provide superior mass transfer and greater control over critical process parameters. Additional technologies like alternating tangential flow filtration help maintain sterility while recovering and reusing conditioned media. Real-time process analyzers and advanced process analytical technologies ensure robust quality assurance.

Improving Process Economy And Yields

By allowing constant production over extended periods, continuous processes significantly boost overall equipment effectiveness. They utilize reactor volume more efficiently at a fraction of capital investment for an equivalent batch plant. Without downtime between campaigns, the utilization of expensive manufacturing assets increases from 15-20% for batch to over 80% for continuous operations. Higher cell densities and prolonged growth cycles also improve space-time yield - a critical economic metric - by over 10-fold compared to batch. Continuous chromatography enables smaller, cheaper columns to be re-used instead of single-use resins. All these factors deliver substantial cost savings.

Challenges In Implementation

While offering immense potential rewards, transitioning to true continuous mode is difficult in practice and requires resolving several technical challenges. Maintaining stable physiological conditions over prolonged runs, without unintended evolution of cell lines, is crucial. Developing robust control strategies to handle upstream and downstream operations in a tightly integrated way is also complex. Ensuring sterility across interconnected, always-on systems demands innovative solutions. Further work on single-use technologies suited for continuous processing can help address these issues and smooth commercialization.

Regulatory Considerations

Regulatory approvals present a hurdle for novel production platforms. However, continuous manufacturing is gaining acceptance owing to its quality advantages. Demonstrating robustness, reproducibility and real-time monitoring capabilities improves regulatory confidence in the technology. Establishing science and risk-based approaches for validation and control strategy review facilitates its implementation. Some agencies now exempt continuous runs from a maximum batch limit if proven equivalent to multiple batches. With ongoing regulatory dialog and as more continuous processes commercialize, approvals should become more flexible and predictable in future.

Future Prospects

As a disruptive technology promising substantial economic and sustainability benefits, continuous bioprocessing will transform biomanufacturing landscape in coming years. Its application will extend beyond therapeutic proteins to include vaccines, complex biosimilars and biochemicals. Combining process intensification with other emerging technologies like modular facilities, single-use equipment and digital transformation will further cement its preeminence. Continuous biomanufacturing is a key enabler for achieving 's ambitions of more affordable, accessible healthcare worldwide through industrial-scale "biofactories of the future".

Get more insights on this topic:  https://www.zupyak.com/p/4265469/t/continuous-bioprocessing-a-viable-alternative-to-batch-processing

Author Bio:

Alice Mutum is a seasoned senior content editor at Coherent Market Insights, leveraging extensive expertise gained from her previous role as a content writer. With seven years in content development, Alice masterfully employs SEO best practices and cutting-edge digital marketing strategies to craft high-ranking, impactful content. As an editor, she meticulously ensures flawless grammar and punctuation, precise data accuracy, and perfect alignment with audience needs in every research report. Alice's dedication to excellence and her strategic approach to content make her an invaluable asset in the world of market insights. (LinkedIn: www.linkedin.com/in/alice-mutum-3b247b137 )

*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it