Continuous biomanufacturing – Key drivers for adoption, economic modelling and regulatory considerations

The Medicine Maker recently published a multi-authored eBook on Continuous Biomanufacturing, titled, “The Continuous Way”. The publication includes seven articles covering the topic of continuous biomanufacturing from a variety of angles. I really enjoyed the eBook and it provided a great update on the current state of continuous biomanufacturing as well as information about key drivers for adoption, new economic modeling, and integration of continuous operations. Following is a sampling of articles with key highlights.

Embracing Continuous Biomanufacturing

The eBook begins with a foreword by Dr. Peter Levison, “ A New Chapter for Continuous Biomanufacturing,” which provides an excellent high-level overview of the evolution of continuous biomanufacturing as well as recent technology developments that are making the implementation of continuous biomanufacturing not just possible, but truly beneficial. Key technologies in this area include: diafiltration solutions, continuous chromatography, and acoustic wave separation to enable continuous clarification. In addition, the increase of available data and economic modeling allows companies to really examine the possible benefits of continuous biomanufacturing in a way that previously wasn’t possible.

Drivers for Continous Biomanufacturing Adoption

Dr. Howard Levine, President and CEO of BioProcess Technology Consultants, Inc wrote a very interesting article, titled “Driving the Move to Continuous Bioprocessing”. The article provided a comprehensive summary of the key drivers of continuous biomanufacturing adoption. More than ever before, the biopharmaceutical industry needs flexible manufacturing. On one side there is the need to produce large quantities of some high indication products to meet global demand, while on the other side there has also been an increase in producing drugs for low product volume indications, or niche markets. Continuous biomanufacturing provides manufacturers with more flexibility than batch processing can, and this could permit the efficient and cost-effective manufacture of product at a wide range of scale. Continuous biomanufacturing also enables higher rates of equipment and facility utilization and smaller facilities overall. He identifies the key benefits of continuous biomanufacturing as having increased flexibility, better cost-efficiency, and improved overall product quality and consistency. Dr. Levine believes that some of the most persistent problems that the industry faces just can’t be solved under batch manufacturing, which is why we need to embrace solutions like continuous biomanufacturing.

Economic Modeling to Support Adoption

“In Economical Truths” Mark Schofield and Jonathan Hummel discuss the ways in which manufacturers must use data and modeling in deciding whether continuous biomanufacturing is a good fit for their process. The authors discuss how historically cost reduction has not been a top priority for biopharmaceutical manufacturing; instead the focus was on quality, safety and time to market. With increasing pressure to reduce the cost of drugs, cost reduction strategies are now a primary focus and continuous biomanufacturing provides the greatest opportunity for significant reduction of manufacturing costs. Of course understanding whether these reductions are possible requires cutting edge modeling where all variables can be considered. In this article, the authors describe new economic models that can compare the relative costs of continuous process, single-use batch and stainless steel downstream processes in monoclonal antibody production. The article provides some very impressive data regarding the cost reductions that can be achieved using continuous biomanufacturing in different scenarios.

Technologies to Enable Continuous Biomanufacturing

In the article, “In Pole Position,” Martin Smith and Mario Philips describe why Pall Biotech decided to commit to continuous biomanufacturing a few years ago and how they have developed innovative technologies and equipment to facilitate a continuous biomanufacturing process. They describe how it was not enough to simply put together existing technologies, but to really deliver on the benefits of continuous biomanufacturing, new technologies and systems specifically designed for continuous operations had to be developed. Pall has re-engineered every stage of the downstream biopharmaceutical process to create a fully end-to-end in-house manufacturing system in Westborough, MA. By the end of 2017, they had also launched a range of continuous systems to allow customers to remain in continuous mode from process development through to fully scaled-up operations.

In the article, “Continuous Success: Establishing a Continuous Bioprocess Platform,” authors discuss in more detail specific technologies that have enabled an end-to-end process, including acoustic wave separation and continuous chromatography. In addition, Pall Biotech has utilized their extensive experience with continuous biomanufacturing to create tools to help customers with process development for continuous processes and are able to utilize data that they have collected internally to help end-users create successful and efficient process development programs.

One of the most important continuous operations in downstream is chromatography. In the article, “Continuous Chromatography: Workhorse and Racehorse,” authors describe the challenges with batch chromatography and the substantial benefits that can be gained by implementing a continuous chromatography process. They present a study where the Cadence™ BioSMB continuous chromatography system is tested using multiple scenarios with different column configurations. To optimize the process they chose a titer that was indicative of the upstream process and then optimized the number of columns that should be run in parallel to match the titer input. Optimizing the number of columns run in parallel in a continuous biomanufacturing system provided many benefits including: reduction in the amount of sorbent used, faster flow rates and/or higher feed concentrations, plus the labor savings inherent in a continuous process.

Regulatory Considerations

In “Continuous Processing is Still Processing,” Mani Krishnan and Marc Bisschops discuss the regulatory considerations when implementing continuous biomanufacturing. Whilst continuous biomanufacturing isn’t inherently riskier, just like in batch manufacturing it is important to understand the areas of risk and have plans in place to mitigate these risks. Current regulations make no distinction between continuous and batch biomanufacturing. In fact, continuous processes provide manufacturers more information about and a better understanding of their process overall, which ultimately enables higher manufacturing consistency and product quality. Authors point out that it is important for suppliers, the company and regulators to work together to understand any areas of concern and to create appropriate solutions. Regulators are encouraging innovation that improves manufacturing and continuous biomanufacturing is no exception.

Future of Biomanufacturing

The eBook closes with a published interview with Charles Cooney, Robert T. Haslam (1911) Professor of Chemical and Biochemical Engineering, Emeritus, Department of Chemical Engineering, Massachusetts Institute of Technology, titled, “Buying into the future”. In the interview Prof. Cooney talks about why the industry has been slow to implement continuous biomanufacturing and what the future looks like. He talks about how the integration of continuous operations is key in fully implementing continuous biomanufacturing and how academics, biopharmaceutical manufacturers and technology suppliers need to work together. He also believes that advances in analytical sciences are important areas that need to be further developed, as it is the “vocabulary for manufacturers, scientists, and regulators to have meaningful conversations”.

For more information and the full articles please see The Continuous Way

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