Manufacturing Strategy in Pharma: Scale-Up vs. Scale-Out for Continuous Processes 

As pharmaceutical pipelines evolve, manufacturing strategies are being tested in new ways. Drug candidates are more complex, development timelines are tighter, and expectations for quality and consistency continue to rise. Against this backdrop, one question comes up repeatedly for formulation and manufacturing teams: should we scale up, or should we scale out? 

During one of our recent educational webinars on pharmaceutical extrusion and continuous manufacturing, this question emerged as a central theme. The discussion reflected a broader industry shift. Traditional assumptions about scale-up do not always hold for modern formulations, particularly those involving poorly soluble APIs, amorphous systems, and continuous processes. 

Understanding the difference between scale-up and scale-out, and when each approach makes sense, is becoming increasingly important. 

Scale-Up vs. Scale-Out: What’s the Difference? 

In pharmaceutical manufacturing, scale-up typically means increasing output by moving to larger, higher-throughput equipment while keeping the same basic process. Scale-out, by contrast, increases capacity by replicating a proven process across multiple identical units or by extending run time, rather than increasing equipment size. 

Put simply, scale-up makes the machine bigger, while scale-out makes more of the same machine. Both approaches are widely used, but they introduce very different technical, operational, and risk considerations. 

Why Scale-Up Is More Challenging Today 

For decades, pharmaceutical manufacturing relied heavily on batch processing and linear scale-up logic. Increase vessel size, adjust parameters, validate, and move forward. In many cases, that approach worked well. 

Today, however, formulations are more sensitive. Many modern drug products depend on precise control of heat, shear, mixing, and residence time. When equipment size increases, these factors do not always scale proportionally. 

Peer-reviewed research on hot-melt extrusion (HME) and twin-screw extrusion shows that heat generation, heat transfer, and mechanical energy input can change significantly with scale. Larger systems may experience higher internal temperatures or altered residence time distributions, which can affect amorphous stability, granule properties, or overall product quality. 

As a result, scale-up is no longer purely an engineering exercise. It is a formulation and process design challenge. 

Continuous Manufacturing Changes the Decision Framework 

Continuous manufacturing has gained momentum because it addresses many of the limitations of traditional batch scale-up. Rather than producing material in discrete lots, continuous processes feed, transform, and discharge material in a controlled, steady flow. 

Extrusion-based technologies, including hot-melt extrusion and twin-screw granulation, are central to this shift. Twin-screw extruders offer precise control over critical parameters such as temperature, shear, mixing intensity, and residence time. This level of control is especially valuable for complex or sensitive formulations. 

Just as importantly, continuous manufacturing decouples throughput from equipment size. Output can often be increased by running longer, optimizing feed rates, or replicating a validated setup, rather than moving immediately to a larger machine. 

Why Scale-Out Is Gaining Attention 

Scale-out offers a way to increase capacity while preserving known process conditions. By replicating an established extrusion process or operating it for longer production windows, manufacturers can maintain consistent specific mechanical energy, residence time, and mixing behavior. 

From a quality standpoint, this can reduce risk. Because the process remains unchanged, the likelihood of introducing new thermal or mechanical stresses is lower. This is particularly important for formulations that rely on controlled amorphous states or narrowly defined processing windows. 

Scale-out also supports modular manufacturing strategies. Multiple identical lines can be deployed across sites, provide redundancy, and enable more flexible responses to changing demand. For many organizations, this flexibility is just as valuable as maximum single-line throughput. 

When Scale-Up Still Makes Sense 

Scale-up is not obsolete. For high-volume products with robust formulations and well-characterized processes, larger extrusion systems can be efficient and economical. 

The key is understanding the limits. Successful scale-up in extrusion-based processes depends on careful control of screw design, degree of fill, specific mechanical energy, and heat transfer. When these factors are well understood and managed, scale-up can be predictable and reliable. 

However, achieving that level of confidence takes data, experience, and robust process understanding. For many early- and mid-stage programs, scale-out may offer a faster and lower-risk path. 

Extrusion as an Enabler, Not a Constraint 

One important takeaway from both the webinar discussion and the scientific literature is that extrusion platforms support both scale-up and scale-out strategies. Twin-screw extrusion systems are inherently modular and continuous, allowing manufacturers to choose the approach that best fits product risk, demand, and lifecycle stage. 

Rather than locking teams into a single path, extrusion enables manufacturing strategies that can evolve alongside the product. 

Designing Manufacturing Strategy from the Start 

The choice between scale-up and scale-out should not be made late in development. It should be considered alongside formulation design, process selection, and long-term manufacturing goals. 

As discussed in our webinar, the most resilient strategies are those that prioritize flexibility early. For many modern drug candidates, especially those requiring precise control over solubility or microstructure, that flexibility can be a decisive advantage. 

Designing with continuous manufacturing and extrusion technologies in mind gives teams options, whether the right answer turns out to be scale-up, scale-out, or a combination of both. 

Watch Webinar

Additional Resources 

• Video: Hot-Melt Extrusion for Pharmaceutical Applications; Technology for Solubility, Scale-Up, and Novel Dosage Forms: https://players.brightcove.net/3663210762001/08UsfMRkC_default/index.html?videoId=6387948674112&interactivityProjectId=696e759d6740d8db7b10b0c9

• Article: Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation—Where Are We Now? https://link.springer.com/article/10.1208/s12249-024-02749-2 

• Continuous Manufacturing and Granulation Technologies and Instruments: https://www.thermofisher.com/us/en/home/industrial/manufacturing-processing/improving-pharmaceutical-biotech-manufacturing-processes-production-methods/technologies/continuous-granulation.html 
• Pharmaceutical Extrusion Systems: https://www.thermofisher.com/us/en/home/industrial/manufacturing-processing/extrusion-compounding-equipment/instruments/pharma.html?icid=CAD_blog_LSM_2026Jan
• Extrusion-based technologies: https://www.thermofisher.com/us/en/home/industrial/manufacturing-processing/extrusion-compounding-equipment.html?icid=CAD_blog_LSM_2026Jan

FAQ: Scale-Up, Scale-Out, and Extrusion 

What is scale-up in pharmaceutical manufacturing? 
Scale-up involves increasing output by moving to larger equipment while maintaining the same process concept. 

What is scale-out in pharmaceutical manufacturing? 
Scale-out increases capacity by replicating a proven process across multiple identical units or by running the same process for longer periods. 

Is scale-out better than scale-up? 
Not universally. Scale-out often reduces risk for sensitive formulations, while scale-up can be more efficient for high-volume, stable products. 

How does extrusion support both approaches? 
Extrusion technologies provide precise process control and modularity, making them suitable for both scale-up and scale-out strategies in continuous manufacturing.