Adopting Continuous Bioprocessing For Sustainable Production Of Biologics

The biopharmaceutical has traditionally relied on batch manufacturing for the production of therapeutic proteins and antibodies. However, batch processes are inefficient with long cycle times, high production costs and quality inconsistency between batches. There is a growing realisation in the continuous manufacturing offers several advantages over batch processes. Continuous processes allow for real-time monitoring and control of critical process parameters, resulting in greater productivity, reduced costs and improved product quality.

Continuous Vs Batch Manufacturing

In a batch process, all steps such as cell culture, harvest, purification etc. are carried out sequentially in the same equipment. The process has to be stopped, the equipment cleaned and then restarted for the next batch. This leads to longcycle times of 6-12 months for a single batch.

In contrast, continuous manufacturing integrates and combines different bioprocess units enabling uninterrupted production. The key steps of cell culture, harvest and purification can be carried out simultaneously in a continuous manner. Material continuously flows through the interconnected process units. This results in significantly higher productivity and capacity utilisation as equipment and personnel time is not wasted between batches for cleaning and validation. Continuous processes can reduce production time from several months to just a few weeks.

Regulatory Acceptance And Technology Readiness

Initially, there were concerns in the whether regulators would accept continuously manufactured products. However, in recent years both FDA and EMA have provided clear guidelines supporting continuous manufacturing. In 2004, FDA issued a guidance on PAT (Process Analytical Technology) encouraging real time monitoring and control for improved quality. This helped drive adoption of continuous processing technologies.

While the technology is rapidly advancing, full end-to-end continuous bioprocessing from cell culture to final drug product is still challenging. Most companies have integrated limited elements of continuity into their processes. For example, utilizing perfusion bioreactors for continuous cell culture or attaching a continuous chromatography step to a batch downstream process. Fully closed and interconnected continuous bioprocessing plants are yet to be realized on an industrial scale.

Advantages Of Continuous Processing

1. Improved process understanding: Continuous processes generate vast amounts of real time data that provides tremendous insight into process behaviour and variability factors. This aids in developing high quality robust processes.
2. Increased flexibility and capacity: Modular process design allows for easy additions or reconfiguration of production capacity based on demand changes. It provides greater scalability than fixed capacity batches.
3. Reduction in product variability: Elimination of batch-to-batch variations results in more consistent critical quality attributes of the final drug product. This has important implications for regulatory compliance and supply chain management.
4. Lower costs of goods: Higher equipment utilisation, smaller facility footprint and lower work-in-process inventories contribute to significantly lower costs of goods potentially up to 50% savings compared to batch processes.
5. Improved environment sustainability: Resources and energy are optimally used with minimum holding of intermediates. Waste generation is reduced due to smaller volumes of intermediates and less cleaning solvents.

Challenges In Implementation

While continuous processing offers clear advantages, full implementation poses technical and operational challenges:

1. Lack of plug-and-play equipment: Standardised modular equipment and control systems suitable for continuous biomanufacturing are still under development.
2. Process development efforts: Significant resources are required to develop, characterise and validate new continuous processes.
3. Control system complexity: Real time control of multiple interconnected process units with feedback loops necessitates more advanced modeling and control strategies.
4. Validation approaches: Novel continuous manufacturing approaches require defining new validation paradigms for approval by health authorities.
5. Technology transfer: Successful technology transfer of continuous processes between labs, pilots and full scale requires extensive experimentation.
6. Supply chain integration: Logistics and supply chain networks need redesign to support just-in-time manufacturing and different inventory models of continuous processing.

Implementing continuous bioprocessing thus requires substantial financial commitment and R&D efforts from companies. However, the long term productivity gains and competitive advantage are driving many biopharma firms to adopt this manufacturing approach particularly for their new product candidates. With support from vendors, regulatory agencies and technology advances, fully continuous biomanufacturing is likely to become the mainstream platform in future.

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

About Author - Alice Mutum

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