How Continuous Bioprocessing Is Shaping Modern Biopharma Manufacturing

By Priyanka Bhendale, assistant manager – Healthcare Market Research, Markets and Markets

The biopharmaceutical industry is experiencing a significant shift toward continuous bioprocessing. Unlike traditional batch processing, which involves discrete stages with intermediate holding tanks, continuous bioprocessing operates seamlessly. Cells are grown and the desired product is continuously extracted and purified in a single connected system. This eliminates downtime between batches and allows for more efficient use of resources and equipment.

According to our published market research, the continuous bioprocessing market is estimated to be worth over $218 million in 2023 and is projected to reach over $599 million by 2028, exhibiting a significant CAGR of 22.4% during the forecast period (2023-28). This growth is mainly driven by factors such as rising demand for biopharmaceuticals; growing adoption of continuous bioprocessing among CDMOs/CMOs for biomanufacturing; and advantages of continuous bioprocessing over batch/fed-batch mode.

Exploring Market Dynamics: PAT-Enabled Optimization Of Continuous Bioprocesses

Process analytical technology (PAT) is a system of analytical tools that are used to monitor and control manufacturing processes.  PAT tools such as spectroscopy, chromatography, and sensor technologies allow for continuous monitoring of critical process parameters (CPPs) and critical quality attributes (CQAs) in real time. This enables manufacturers to promptly detect deviations and make necessary adjustments to maintain process integrity and product quality. PAT enables manufacturers to optimize their processes in several ways:

• Process Understanding and Control: By providing insights into the relationships between process parameters and product attributes, PAT facilitates a deeper understanding of the bioprocessing environment. Manufacturers can use this knowledge to implement advanced control strategies, such as feedback control loops or model predictive control, to optimize process performance and ensure product consistency.
• Reduced Cycle Times and Increased Productivity: PAT-enabled optimization helps streamline bioprocessing operations by identifying opportunities for process intensification and efficiency improvements. By continuously monitoring and optimizing process parameters, manufacturers can reduce cycle times, increase throughput, and enhance overall productivity.
• Quality by Design Implementation: PAT aligns with the principles of quality by design (QbD) by enabling the design of robust processes that consistently deliver products with the desired quality attributes. By integrating PAT tools into the design and development phases, manufacturers can build quality into the process from the outset, minimizing the risk of product failures and deviations.
• Reduced Manufacturing Costs and Waste: Continuous monitoring and control enabled by PAT can help identify and mitigate process inefficiencies, reducing raw material consumption, energy usage, and waste generation. This not only lowers manufacturing costs but also contributes to sustainability goals by minimizing environmental impact.
• Facilitation of Regulatory Compliance: PAT provides manufacturers with the tools and data needed to demonstrate process understanding, control, and consistency to regulatory authorities. By implementing PAT-enabled optimization strategies, manufacturers can streamline regulatory submissions, accelerate product approvals, and ensure compliance with stringent regulatory requirements.

Overall, PAT-enabled optimization serves as a powerful opportunity in the continuous bioprocessing market, encouraging manufacturers to achieve higher levels of process efficiency, quality, and regulatory compliance.

High Productivity And Affordability To Drive Adoption Of Chromatography Systems In Continuous Bioprocessing   

The continuous bioprocessing market is further segmented by product into chromatography systems and consumables; filtration systems and devices; bioreactors; cell culture media, cell lines, buffers, and reagents; and other products. The chromatography systems and consumables include resins, solvents, columns, membranes, buffers, reagents, and other consumables such as autosamplers and fitting and tubing detectors, among others. Continuous chromatography techniques are critical in continuous downstream bioprocessing to achieve high purity for proteins, and these processes are at an advanced level with several opportunities. Continuous operation can be maintained by running multiple chromatography columns in a countercurrent or concurrent manner. This is because the loading is done in the first column, and all the following stages (elution, regeneration, washing, and re-equilibration) are completed in the succeeding columns. The continuous mode of operation includes countercurrent chromatography (CCC), multicolumn countercurrent solvent gradient purification chromatography (MCSGP), countercurrent tangential chromatography (CCT), simulated moving bed (SMB) chromatography, and continuous annular chromatography (CAC).

With an increased demand for biologics, the need for intensification of the upstream bioprocess to boost productivity and lower manufacturing costs has increased. There are several studies published by the National Center for Biotechnology Information (NCBI) showing the successful application of integrated continuous bioprocessing in the production of monoclonal antibodies (mAbs). For instance, a study achieved around 80% increase in productivity by utilizing one-column continuous chromatography (OCC) and perfusion bioreactor culture with alternating tangential flow technology (ATF).

Moreover, manufacturers are increasingly shifting their focus to chromatography systems to streamline their production processes and meet the growing market needs.  In June 2023, Waters Corporation and Sartorius AG announced a collaboration to develop integrated analytical solutions for downstream biomanufacturing. The Sartorius Resolute BioSMB multicolumn chromatography platform and the Waters PATROL UltraPerformance Liquid Chromatography Process Analysis System have hardware and software integrations that will provide bioprocess engineers with more analytical data for batch and continuous downstream manufacturing, increasing yields and reducing waste while lowering biomanufacturing costs.

Focus On Downstream Processing

Downstream processes encompass a series of purification and separation steps aimed at isolating and purifying the desired biopharmaceutical product from the complex mixture of cellular components, media, and contaminants generated during upstream production. These processes typically include products like cell filtration systems and devices, chromatography systems and consumables, and associated accessories and other products. Continuous chromatography systems, in particular, are revolutionizing downstream purification by enabling the continuous separation and purification of biopharmaceutical products with exceptional precision and throughput. Periodic countercurrent chromatography (PCC), MCSGP, continuous CTC, SMB, and aqueous two-phase extraction (ATPS) have been successfully used for continuous capture from process development to manufacturing scale in large biopharma companies to avoid potential process bottlenecks. These technologies improve process efficiency, product quality, and cost of goods. For continuous capture, there are a variety of resins available for the Protein A resin screening step. These include the MabSelect Sure PCC (Cytiva) and Poros ProA (Thermo Fisher Scientific). These technologies are expected to be adopted by more midsize biotech companies and CDMOs in the coming years.

Therefore, growing focus on reducing production costs for biosimilars and innovator drugs; rising technological advancements such as single-pass tangential flow filtration (SPTFF) and multicolumn chromatography; the rising need for intensification of the downstream bioprocess due to increased titer; and the growing demand for biopharmaceuticals are some factors responsible for the segment’s high share in the market.

Application-Based Analysis Of The Continuous Bioprocessing Market

Based on application, the continuous bioprocessing market is segmented into mAbs, vaccines, cell and gene therapy, and other applications. mAbs form one of the largest segments of the biotechnology drugs market. The large share and high growth rate of this segment are attributed to the increasing pharmaceutical R&D drug pipeline; growing focus on continuous bioprocessing in the production of mAbs; the increasing clinical pipeline of monoclonal antibodies; and rising regulatory approvals for therapeutic antibodies.

Continuous bioprocessing is rapidly gaining momentum in monoclonal antibody bioprocessing, providing potential advantages such as smaller facility footprints, lower investment costs, flexibility, and process economies. The commercial success of mammalian cell-derived mAbs has led to the increased demand for novel single-use bioreactor systems that provide greater productivity and flexibility and reduce costs. A study has successfully demonstrated the feasibility of a fully integrated continuous process from pilot scale bioreactor to drug substance, paving the way for its broader adoption in the industry (Source: NCBI). Bayer, Merck, BiosanaPharma, and Genzyme are among the first companies to implement fully integrated end-to-end continuous bioprocessing platforms. Bayer has successfully used its CBP platform to produce a biosimilar mAb (omalizumab) in a fully integrated continuous downstream bioprocess.

Other factors supporting market growth in this segment include the rising incidence of cancer and the growing demand for cancer therapeutics. mAbs offer minimal side effects compared to chemotherapy. For instance, the new emerging classes of more effective and efficient mAbs, such as anti-PCSK9 monotherapy, are also a key factor contributing to market growth. Blockbuster mAbs like Humira, Rituxan, Avastin, and pembrolizumab (Keytruda) are expected to lose their patents in the coming years. The loss of patents has prompted biopharmaceutical companies to incorporate mAbs into their drug manufacturing pipeline. Thus, the increasing pharmaceutical drug pipeline and rising regulatory approvals for mABs are expected to drive the demand for cost-efficient approaches such as continuous bioprocessing.

The Players Operating In Continuous Bioprocessing

Prominent players in the continuous bioprocessing market include:

• Danaher Corporation (U.S.)
• Sartorius AG (Germany)
• Thermo Fisher Scientific Inc. (U.S.)
• Repligen Corporation (U.S.)
• Merck KGaA (Germany)
• 3M Company (U.S.)
• Getinge AB (Sweden)
• Eppendorf SE (Germany)
• Corning Incorporated (U.S.)
• Entegris (U.S.)
• Fujifilm Holdings Corporation (Japan)
• Meissner Filtration Products Inc. (U.S.)
• Kuhner AG (Switzerland)
• Esco Lifesciences Group Ltd. (Singapore)
• Satake Chemical Equipment Mfg. Ltd. (Japan)
• BioNet (Spain)
• Stobbe Group (Switzerland)
• bbi-biotech GmbH (Germany)
• OMNIBRX Biotechnologies (India)

These players, among others, in this market have adopted strategies such as agreements, collaborations, product launches, technology advancements, partnerships, acquisitions, and expansions to expand their global presence and increase their shares in the continuous bioprocessing market. Some of their strategic initiatives are described below:

• In January 2024, Merck KGaA signed a non-binding memorandum of understanding (MoU) with Mycenax Biotech to explore collaboration on bringing innovative and high-capacity bioprocessing solutions to Taiwan and other international markets. The MoU aims to integrate Merck's BioContinuum Platform with Mycenax's bioprocessing solutions, including automation and digitization of processes. The collaboration seeks to bring novel continuous processing solutions to the market, improve Mycenax Biotech’s global position, and meet a wide range of biopharmaceutical needs.
• In November 2023, WuXi Biologics announced that it has completed end-to-end DS manufacture at pilot scale using WuXiUP, a patented ultra-high productivity continuous bioprocessing platform, at its non-GMP pilot plant in Shanghai, China. This well-configured bioprocess is currently being scaled up to GMP manufacturing and will be used across WuXi Biologics' global manufacturing sites in China, Ireland, the United States, and Singapore.
• In August 2023, Sartorius AG collaborated with Repligen Corporation and launched an integrated bioreactor system. This system incorporates Repligen XCell ATF upstream intensification technology into Sartorius’ Biostat STR bioreactor to simplify intensified seed train and N perfusion implementation for biopharmaceutical manufacturers.
• In August 2023, Sartorius AG and Emerson collaborated to integrate Sartorius’ Biostat STR Generation 3 family of bioreactors with Emerson’s DeltaV distributed control system (DCS). This integration is expected to reduce the need for manual operation, which will increase the quality and speed for time to market.

Conclusion

The continuous bioprocessing market stands at the forefront of innovation, poised to revolutionize pharmaceutical manufacturing practices globally. With its seamless, uninterrupted production flow, continuous bioprocessing offers unparalleled advantages in efficiency, productivity, and quality control compared to traditional batch processes. The market is driven by a confluence of factors, including increasing demand for biopharmaceuticals, emergence of integrated end-to-end continuous bioprocessing, favorable regulatory and government initiatives for innovative technologies, and growing adoption among CDMOs and CMOs. As pharmaceutical manufacturers continue to embrace continuous manufacturing practices, the market is witnessing rapid expansion and diversification. From upstream cell culture and fermentation to downstream purification and formulation, continuous bioprocessing solutions are being deployed across the entire biopharmaceutical production workflow. Moreover, the integration of process analytical technology (PAT) and automation further enhances process control and optimization, driving efficiency and ensuring regulatory compliance.

About The Author:

Priyanka Bhendale has more than nine years’ experience in healthcare market research and consulting across pharmaceutical, biotechnology, and medical devices verticals. She acquired knowledge and expertise in market assessment, market sizing and forecasting, end user perception analysis, opportunity analysis, and competitive intelligence studies and has worked on the growth engagements across bioprocessing technologies, cell culture technologies, contract research and manufacturing.