How CDMOs Are Driving the Adoption of Continuous Biomanufacturing
Biopharma companies are increasingly dependent on CDMOs to streamline production, enhance efficiency, and accelerate drug development. As therapies become more complex and regulatory demands grow, the ability to outsource manufacturing to a trusted partner has never been more essential.
However, with a rapidly expanding pool of CDMOs offering specialized services, choosing the right partner can be a daunting task. For existing CDMOs, the market is becoming crowded and increasingly competitive, forcing them to embrace innovative solutions that make them stand out from the crowd. One of the recent advancements gaining traction is continuous biomanufacturing. A growing number of CDMOs are integrating this approach to replace traditional batch manufacturing with a seamless, real-time production process.
But what exactly is continuous biomanufacturing, and how does it compare to traditional batch processing? More importantly, is it truly the game-changer that many in the industry claim it to be?
From Batch to Continuous: The Leap in Biopharmaceutical Manufacturing
Traditionally, the biopharmaceutical industry has favored batch manufacturing as the default method for producing drugs. Yet once the gold standard for manufacturing, it is increasingly falling out of favor because of its inherent inefficiencies.
The batch approach involves multiple discrete steps; each completed before moving on to the next. As a result, this has led to periods of downtime and hold times, which can in turn lead to material degradation and increased costs. In addition, batch production can be more susceptible to issues related to quality, variability, inventory costs, and wastage risk that are caused by potential errors in individual batches. The need for frequent manual interventions also raises the risk of human error, further impacting product consistency and quality.
In contrast, continuous manufacturing integrates all stages of production into a seamless, real-time process. Whilst not a new manufacturing technique, it has gained recent popularity in the pharmaceutical industry within the last decade. This approach maintains stable manufacturing conditions, supports high cell densities, and allows for the continuous removal of waste, leading to higher productivity and improved process economics.
When considering continuous manufacturing compared to batch manufacturing, the advantages are clear:
Speed and Agility: Enables faster production cycles and quicker responses to market demands and allowing biopharma companies to manage supply chains more effectively to ensure consistent product availability.
Cost Savings: By reducing waste and operational costs, continuous manufacturing provides significant savings - for both manufacturers and CDMOs - that can be reinvested into R&D, driving innovation and growth.
Quality Consistency: Combined with data analytics, product quality remains consistent and reduces the risk of errors and recalls.
Flexibility: Continuous manufacturing allows for production in smaller, modular facilities that are more responsive to fluctuations in market demands. Requiring a smaller footprint, they are theoretically easier to build and deploy across multiple locations.
How Continuous Manufacturing is Shaping the Future of Therapeutic Production
The applications of continuous manufacturing in biopharma are diverse across multiple therapeutic areas.
For monoclonal antibodies (mAbs), continuous processing ensures consistent yields and quality by maintaining steady-state conditions throughout production to minimize batch variability, improve efficiency, and enhance scalability – all of which are particularly valuable for high-demand biologics.
Vaccine manufacturing has also seen major benefits from continuous processes, especially in response to global health crises. The pandemic accelerated interest in this approach, with companies such as Janssen and Sanofi exploring continuous manufacturing to streamline vaccine production.
For cell and gene therapies, continuous manufacturing offers precise control over culture conditions to ensure product consistency and improve overall yields. With CGT requiring highly controlled environments, companies like Novartis and Bluebird Bio have successfully implemented continuous processing techniques to enhance efficiency in CAR-T and gene therapy production.
As continuous biomanufacturing gains traction, more companies are investing in this innovative approach to drive efficiency, reduce costs, and improve therapeutic access.
The CDMOs Already Offering Continuous Manufacturing
Elsewhere, many other CDMOs are leveraging continuous manufacturing to transform their operations. CDMOs such as WuXi Biologics, Lonza, and Samsung Biologics are already investing heavily in continuous manufacturing infrastructure to demonstrate that continuous production is not just an emerging trend.
Many more CDMOs are already leveraging continuous manufacturing to transform their operations:
In Pune, India, Enzene Biosciences developed the modular EnzeneX™ 2.0 platform, which reduces the equipment footprint compared with that of conventional fed-batch systems. It is capable of clinical phase cGMP supply from as low as 30-liter scale, with variable bioreactor capacity to accommodate scale-on and scale-out expansion. Building on its success, Enzene will soon launch a new state-of-the-art manufacturing facility in Hopewell, New Jersey, where it will introduce the company’s patented, fully-connected continuous manufacturing™ (FCCM™) platform to the U.S.
Amgen's Next-Generation Biomanufacturing Facility in Singapore is a prime example. The facility uses single-use bioreactors and real-time quality analysis, boasting a modular design that reduces resource usage and increases bulk production capabilities.
The Continuous 2 project by CPI (Centre for Process Innovation) demonstrates the potential of continuous manufacturing for biotherapeutics. This project integrated advanced technologies like automation and cloud software to create a sustainable, efficient, and decentralized production model. It achieved significant reductions in analysis time and demonstrated cost-effectiveness and resource efficiency.
However, questions remain about the full impact of continuous manufacturing on regulatory processes and industry-wide adoption.
Embracing the Future: Challenges and Opportunities in Continuous Manufacturing
As biopharma companies consider adopting continuous manufacturing, whilst the benefits are clear, there are still significant benefits and substantial challenges to overcome.
Whilst CDMOs are increasingly eager to offer continuous manufacturing services to their clients, implementing this is a complex and challenging affair. The high upfront costs of acquiring and integrating the necessary advanced technologies and equipment can be a significant barrier due to the substantial investments in staff training and hiring specialized personnel, who can manage and optimize these sophisticated processes. The time required to design, validate, and scale up continuous processes is also considerable - often taking years to fully implement.
But as CDMOs continue to overcome the complexities of implementing continuous manufacturing, they will be vital in transforming the biopharmaceutical manufacturing industry. Eventually, more CDMOs will be able to offer continuous manufacturing and help biopharma companies reap the rewards of this innovative approach, yet even with CDMO expertise, the transition will not be without its hurdles.
One of the primary challenges for companies with established batch manufacturing systems is the fundamental shift in operational mindset from linear to integrated processes. The need for advanced process control strategies and real-time data analytics adds further complexity to the switching of well-established processes. Another challenge is the regulatory uncertainty. While regulatory agencies like the FDA are supportive, there is still a lack of clear guidelines and precedents for continuous processes, which can deter companies from making the switch.
It's also important to consider the potential drawbacks of relying heavily on CDMOs for continuous manufacturing.
While CDMOs can provide the necessary expertise and infrastructure, they may also introduce additional logistical complexities and dependencies. For instance, integrating continuous manufacturing processes into existing supply chains can be challenging, and the reliance on external partners may limit a company's ability to adapt quickly to internal changes or unexpected market shifts.
Regardless, the shift toward continuous biomanufacturing is well underway and the transition promises to revolutionize the production of biologics. CDMOs that recognize this trend and invest in continuous biomanufacturing will undoubtedly position themselves as leaders in the industry's future and are also likely to offer significant benefits to the companies that choose to partner with them.