Continuous biomanufacturing has rapidly become a vital strategy for pharmaceutical and biotech companies, offering substantial benefits such as cost reduction, faster production timelines, and enhanced process efficiency. Initially introduced in the 1980s, the technology has significantly evolved, now being applied to both upstream and downstream processes. Companies today are keen to adopt continuous manufacturing for its potential to improve productivity and reduce time to market.

In this article, we’ll explore the fundamentals of continuous biomanufacturing, provide key strategies for its successful implementation, and discuss the challenges organisations face in maintaining these processes over time.

What is Continuous Biomanufacturing?

Continuous biomanufacturing refers to the continuous production of biologics, where the production system runs for extended periods, unlike traditional batch manufacturing. This approach is particularly advantageous for producing unstable molecules, which cannot be easily handled in batch processes. According to Margie Holster, an expert in the field, continuous systems, especially perfusion-based systems in upstream processing, allow for shorter residence times, which are critical for maintaining the stability of certain molecules.

Holster emphasises that continuous biomanufacturing is now being applied across the entire biomanufacturing process, extending to downstream and formulation stages. This offers numerous advantages, including:

1. Cost Efficiency: Continuous processes allow companies to reduce the size and complexity of their manufacturing operations, saving costs associated with space, equipment, and energy consumption.
2. Faster Timelines: By eliminating the need for multiple scale-up phases, continuous production allows for quicker transitions from pilot operations to large-scale production, facilitating faster clinical trials and regulatory approvals.
3. Enhanced Monitoring and Control: Advanced monitoring technologies are essential for continuous manufacturing, allowing companies to oversee both product quality and process parameters in real-time.

Key Technologies Enabling Continuous Biomanufacturing

Continuous biomanufacturing depends on several emerging technologies that improve both upstream and downstream operations. The integration of these technologies is critical to ensuring process efficiency and product quality:

1. Advanced Process Monitoring: Effective continuous biomanufacturing requires real-time monitoring of various production parameters. New technologies allow for constant oversight of the product’s quality, helping to ensure that deviations or errors are detected early.
2. Innovative Equipment: Specialised equipment designed for continuous operations enables both upstream (e.g., perfusion bioreactors) and downstream processes to run seamlessly. Advances in filtration, chromatography, and formulation technologies further support these operations.
3. Regulatory Guidelines: The regulatory framework for continuous manufacturing is evolving. The recent introduction of the ICHQ13 guideline highlights the growing acceptance of continuous biomanufacturing by regulatory authorities. This guideline, which is set to come into effect in Europe in June 2024, outlines expectations for continuous production and provides companies with a roadmap for compliance.

Strategic Implementation: Key Steps to Success

For companies looking to transition from traditional batch processing to continuous biomanufacturing, careful planning and strategy are essential. Holster offers the following advice for companies to implement continuous biomanufacturing successfully:

1. Evaluate Your Molecule and Development Cycle: The feasibility of continuous manufacturing depends on the molecule being produced and the stage of its development. Not all biologics are suitable for continuous processing, so an early-stage assessment is crucial. Companies should assess whether their current cell lines and purity requirements are compatible with continuous operations.
2. Adopt a Step-by-Step Approach: Rather than fully transitioning to continuous biomanufacturing in one go, companies should consider a gradual, phased implementation. Many organisations start by applying continuous principles in upstream processes, such as using perfusion bioreactors, and then progressively extend these methods to downstream steps like purification and formulation.
3. Leverage Technology and Innovation: Technological innovation is at the heart of continuous biomanufacturing. Companies should invest in process monitoring and control systems to maintain product quality and consistency throughout the manufacturing cycle. Exploring new equipment and software solutions that enable seamless connectivity between different stages of the manufacturing process is also critical.

Challenges in Maintaining Continuous Biomanufacturing

While continuous biomanufacturing presents clear advantages, companies already using these systems face several challenges in maintaining process stability and compliance. Holster identifies the following as key issues that require ongoing attention:

1. Ensuring Traceability and Quality: In continuous systems, the ability to define and trace each “batch” of product is essential. Regulatory agencies require robust systems that allow companies to track deviations, monitor the impact of those deviations, and ensure that they do not compromise product quality. This involves implementing strong quality control frameworks that support real-time data collection and analysis.
2. Process Stability: Maintaining stability over extended production periods is another significant challenge. Companies must demonstrate that the product remains consistent in terms of quality and efficacy throughout the manufacturing process. This requires regular assessments of process performance and continuous validation to meet regulatory expectations.
3. Integration of Software and Equipment: Continuous manufacturing requires seamless connectivity between various units within the manufacturing line. This includes the integration of equipment, software, and control systems to ensure smooth transitions between process steps. Companies must also focus on validating these integrated systems, ensuring that they meet regulatory standards for process characterisation and product quality.

Conclusion

Continuous biomanufacturing represents a transformative shift in the production of biologics, offering companies the potential for significant cost savings, faster production timelines, and improved quality control. However, successful implementation requires careful planning, a strategic approach to technology adoption, and a focus on regulatory compliance.

By following best practices—such as evaluating molecules early in the development process, adopting a step-by-step implementation strategy, and investing in advanced monitoring technologies—companies can unlock the full potential of continuous biomanufacturing. As regulatory frameworks like ICHQ13 continue to evolve, the future of continuous biomanufacturing looks increasingly promising, allowing for faster, more efficient production of life-saving therapies.

Watch the interview below:

Written by Educo Life Sciences Expert, Margit Holzer

Dr Margit Holzer has over 25 years of experience in the industry and worked on more than 50 different products. She is a specialist in process, product and analytical method development for biopharmaceuticals. She has extensive expertise in bioprocess in all phases of development including preclinical production, clinical production and large-scale commercial supply.

Margit has delivered multiple courses on bioprocess validation. She has helped delegates understand the guidelines and the steps they must take to ensure their operations are compliant. Drawing on her extensive experience Margit provides numerous case studies, examples and exercises during the course.

This article was written from the video interview conducted with Margit  (you can watch it above).