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Continuous manufacturing
Continuous manufacturing offers many opportunities to overcome the challenges of traditional batch production of tablets and capsules. The method is efficient and inherently scalable, and scalable and has advanced to a point of true reliability and flexibility. Continuous manufacturing techniques can be implemented all at once, or a little at a time.
The future of oral drug manufacturing
Most oral drugs are available as tablets and capsules because it’s easy to store and to consume medicine in this form. Traditionally pharmaceutical manufacturers have created such oral dosage forms in batches. Now, many are considering a continuous manufacturing process.
Set up continuous manufacturing so it really works!
Establishing a successful continuous twin-screw granulation (TSG) process can be tricky. Download this free whitepaper with expert advice for process design, development and scale-up for pharmaceuticals. The paper even includes information about how the parameters of twin-screw extruders can impact scale-up of a continuous process.
Understanding the flow behavior of powders and granules is a crucial step when setting up and optimizing a continuous twin-screw granulation process. Powder rheology can help manufacturers understand and optimize this critical parameter that impacts product performance.
- Assure uniform feeding by adjusting feed rates in response to flow behavior
- Avoid segregation of materials brought about by uneven feed levels
- Optimize screw design and minimize power consumption
By thoroughly understanding and monitoring the rheological properties of the powder, manufacturers can optimize the continuous granulation process, improve product quality, and achieve more efficient and stable production with a twin-screw extruder.
Set Up Continuous Manufacturing for Optimal Performance
Understanding the flow behavior of powders and granules is crucial when setting up and optimizing a continuous twin-screw granulation process. Powder rheology helps to understand and optimize this critical material parameter, impacting product performance.
Key Steps:
- Assure uniform feeding
- Avoid segregation
- Optimize screw design and minimize power consumption
By thoroughly understanding and monitoring the rheological properties of the powder, manufacturers can optimize the continuous granulation process, improve product quality, and achieve more efficient and stable production with a twin-screw extruder.
Continuous manufacturing system advantages
Small, medium, and large batches of pharmaceuticals are prone to variations and expensive delays:
- Manual steps invite human error
- Transportation from one step to the next may cause material segregation
- Time-consuming disassembly and cleaning delay production
- Production scale-up requires bigger, more expensive equipment
Continuous manufacturing reduces/eliminates the issues above and makes subsequent tableting easier. With online monitoring, continuous manufacturing also enables drugs to be released as soon as they’re manufactured – there’s no waiting on analytical results before products can ship.
Today, continuous manufacturing is no longer an “untested” process. Companies have gained experience and proven that it can be successfully implemented with a significant positive impact. Numerous commercial products are available that are being produced in a continuous process.
Batch processing in the pharmaceutical industry
It can seem daunting to move away from the batch processing, which has served pharmaceutical manufacturers well for so many years. Questions arise when looking at a new process:
- Will I lose flexibility for producing multiple products?
- How will I characterize the homogeneity of my mix?
Flexibility: There is great flexibility in continuous manufacturing. Switching production from one drug product to another is possible with quick, easy replacement of product contact parts to eliminate the risk of cross-contamination. And modularity allows the granulator to be easily set up for a different product’s required process steps.
Characterizing homogeneity: Online analytical technologies (e.g., near infrared or NIR spectroscopy) allow manufacturers to characterize homogeneity and other material properties at any time in the process. So, the ability to characterize properties is maintained in continuous manufacturing via online analyzers.
Continuous processing in pharmaceutical manufacturing
Quantum leap vs. Slow migration
Continuous processing in pharmaceutical manufacturing can be used from the mixing of initial powders to the packaging of final tablets. This continuous processing can be done with a twin-screw extruder and subsequent drying in a fluidized bed system.
So, the starting point can be small: a stand-alone twin-screw granulator. If more granules are needed, simply run the instrument continuously for a longer period of time.
Modules can be added along the way, expanding the parts of the process that operate continuously:
- Dosing systems
- Dryers
- Tablet presses
A full continuous system can be grown module by module or be put into place all at once with an entire processing line installation. Such installations often take place by scale-out or scale-up.
Scale-out is possible by creating other small copycat systems in different locations, or simply running the process on one instrument scale for a longer time.
Scale-up is done by transferring the process to high-volume, high-speed production systems.
Thermo Scientific pharmaceutical twin-screw extruders are designed to bring you the benefits of continuous manufacturing, whatever your pace may be.
We offer 11 mm, 16 mm and 24 mm pharmaceutical extruders that can stand alone or be partially or fully integrated into your manufacturing process. Systems are available for dual twin-screw granulation (TSG), hot-melt extrusion (HME) processes, or for dedicated TSG. Modules expand their use throughout the process from raw materials to tableting.
Featured products for continuous granulation
Frequently asked questions
ICH Q13 describes continuous manufacturing as the continuous feeding of input materials, transformation of in-process materials, and concurrent removal of output materials. Twin-screw extrusion processes, including both hot-melt extrusion (HME) and twin-screw granulation (TSG), are inherently continuous. These operations can be used as stand-alone continuous processes or integrated with connected steps such as feeding, drying, and tableting, while maintaining appropriate batch definition, process control, and material traceability.
Batch manufacturing processes a defined quantity through discrete steps, often with transfers and manual handling between operations. Continuous manufacturing continuously feeds, transforms, and removes material, enabling flexible adaptation of batch size to market demand. Reduced manual intervention can lower handling-related errors, while appropriate process analytical technology (PAT) can support real-time monitoring and adjustment during operation, helping accelerate development cycles. Continuous processes still require defined batches, traceability, robust control strategies, and compliance with applicable quality and regulatory requirements.
Scientific and regulatory considerations for continuous manufacturing
Twin-screw granulation (TSG) uses a co-rotating twin-screw extruder as a continuous, high-shear mixer to convert a controlled powder feed into granules. Depending on the process, liquid addition or thermal input can be used. Screw configuration, feed rate, liquid-to-solid ratio, barrel conditions, and material properties influence granule attributes. TSG can operate as a stand-alone process step or connect with upstream and downstream operations to form a complete continuous manufacturing process.
Process analytical technology (PAT) tools can be integrated in-line, on-line, or at-line with Thermo Scientific twin-screw extruders to monitor critical material and process attributes during both HME and TSG. Techniques such as FT-NIR spectroscopy can assess attributes including blend homogeneity, moisture, or product quality. Sensor location, calibration, data handling, and control actions are application-specific. PAT data can support process monitoring, development, and automated control strategies, but PAT alone does not establish eligibility for real-time release testing.
A batch-to-continuous transition should begin with material characterization and a clear product and process control strategy. Key considerations include feeding consistency, segregation risk, process dynamics and residence-time distribution, specific mechanical energy, traceability and material diversion, cleaning and changeover, downstream capacity, and batch-size definition. Teams should also plan process validation, pharmaceutical quality system changes, and lifecycle management in line with ICH Q13. Implementation may be staged rather than converting the entire line at once.
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