4 Steps To Process Intensification Success In Biomanufacturing

The next era of biomanufacturing will be characterized by digitalization and automation designed to support more complex product portfolios and workflows. This shift builds on decades of evolution in mAb manufacturing, which has progressed from traditional fed-batch processes in large stainless-steel tanks to the adoption of single-use technology and smaller batch processes. Now, advanced technologies are further transforming production, enabling manufacturers to produce mAbs and emerging biologic modalities more efficiently and at lower costs.

The International Society for Pharmaceutical Engineering (ISPE) coined the concept of Pharma 4.0™, a pharma-specific offshoot of Industry 4.0 that encompasses holistic digital approaches that lend themselves to process intensification (PI), a genre of manufacturing defined by efforts to reduce facility footprint and operational costs while improving product quality. Continuous processes leverage technologies such as perfusion bioreactors, membrane chromatography, data analytics, and advanced automation to increase throughput while reducing downtime and waste across manufacturing workflows.

If weighing the impact of continuous process implementation on your program, first consider the key steps to success, including how to approach adoption, navigate scale-up challenges, identify ideal use cases, and ultimately, reap the benefits.

Step 1. Commit To Intensification As A Long-Term Strategy

With the goal of launching a truly continuous program, every company will need a distinct approach. To accommodate these pathways, there are gradual tiers to implementing PI. By starting with a stepwise approach to semi-continuous or connected process integration, drug sponsors can achieve measurable reductions in facility footprint, cost, and emissions while increasing productivity and building their team’s PI expertise.

Manufacturers and/or CDMOs should begin integrating continuous processes at the development scale to generate the data needed to support scaleup to clinical and commercial manufacturing. With a greater understanding of how intensification can impact workflows, stakeholders will be better prepared for large-scale deployment.

Step 2. Address Scale-Up Challenges

One major challenge of PI adoption is adapting existing spaces to accommodate continuous processes or building new automated facilities; both routes are complex and costly. Furthermore, since continuous manufacturing marks a major shift from traditional fed-batch approaches, legacy systems are often incompatible with continuous operations and must be upgraded prior to launch.

It takes time to successfully integrate and scale a continuous process. In many cases, a drug sponsor’s leadership may prefer the predictive, reliable nature of traditional fed-batch manufacturing to ensure speed to market. CDMOs and sponsors are still exploring how to balance the long-term benefits of intensified process adoption with the ongoing need for scalability, speed, and regulatory compliance. As the industry continues to define PI best practices, clarity around quality control and regulatory compliance will emerge, enabling faster implementation, training, and deployment in the years to come.

Step 3. Apply PI Where It Has Economic Impact

Ultimately, a CDMO and sponsor must collaborate to determine the ideal entry points for continuous manufacturing based on a company’s needs, modalities, and budget. Together, they should evaluate whether the following use cases for continuous processing align with their goals:

• Developing biosimilars: PI can be leveraged to establish early proof of concept and determine product viability as soon as possible.
• Targeting bottlenecks: Continuous manufacturing is used to solve existing facility obstacles, such as mitigating limited buffer capacity and facility size constraints with inline buffer dilution and multi-column chromatography.
• Maximizing throughput: Intensified processes can be applied during perfusion and chromatography steps to capture products immediately, prevent clipping, and generate significantly more product from the same bioreactor.

Step 4. Convert Intensification Into Economic Advantage

When adopted strategically, PI reshapes the economics of biomanufacturing. For sponsors, continuous processing offers critical opportunities to increase productivity, decrease costs, lower carbon footprint, and, most importantly, improve patient access to critical therapies. The economic impact is especially compelling: on average, intensified manufacturing can achieve a COGS of less than 50 €/g for mAbs, a significant price reduction from the mAb manufacturing costs of the 1990s and early 2000s.

Furthermore, intensification efforts enhance manufacturing flexibility and expand geographic access to critical drugs, enabling rapid response to pandemics and outbreaks while mitigating supply chain risks and reducing resource consumption. For these reasons and more, the future of biomanufacturing is closely tied to the capabilities of PI.