The pilot-scale is an important stage for the pharmaceutical manufacturers, it is an indispensable intermediate step after the products have been developed in the R&D labs and before they are ready for commercial production in large volumes. Beside its function for scale-up, the pilot scale is used to manufacture clinical supplies for the clinical trials.
It is well known in the pharma industry that scaling up passes through three stages. It starts from very small quantities of around 1-3 kg on galenical scale. The next step is the pilot scale, required for both, scale-up and clinical trials. The last step is the transfer to the commercial production volume. The transfer between all three stages must ensure to not exceed a ratio of 1:10 in batch size to ensure a consistent process validation.
Beside the mere batch size, the following parameters need to be considered also for a smooth scale-up:
Similar geometry of mixing tools and mixing vessels
Similar Froude numbers
Similar filling ratios
Similar liquid addition rate per kg of product.
Let us assume that a pharma company wants to produce a product in 100 kg batches. At the beginning the product should be developed in the lab-scale, on a 1 kg batch size. During scale-up, the batches should be 10 kg to then be able to scale-up to the production size of 100 kg.
What if the same company wants to produce another product in 250 kg batches? A lab equipment for 2.5 kg can be used, but the pilot equipment for 10 kg (typically a 25 l bowl) would not be adequate anymore, so that a different bowl size is required to be able to process 25 kg equipment.
Since for clinical trials, the pilot scale equipment is used for small scale production, which may require a lot of differing batch sizes and different products in a short period of time.
This example shows the importance of the flexible Rapid Change concept!
DIOSNA’s Rapid Change (Rc) Concept in the Pilot Scale Granulation
The Rapid Change concept in the pilot-scale granulation from Diosna allows a flexible operation and easy to handle moveable modules. The system combines a high-shear mixer/granulator with a fluid bed processor.
The high-shear mixer/granulator used in this case has four different bowl sizes: 10 l, 25 l, 60 l and 80 l. Each bowl size comes as a self-supported mobile module. The drives and control system are installed in the technical area behind the machine in a through-the-wall design. The process modules can be coupled with the drive part in the technical area in just a couple of minutes without tools.
The fluid-bed processor has two different bowl sizes: 30 l and 80 l, which allows to cover the same range as the high-shear mixer/granulator. The bowls are moveable on wheels and can be connected simply and rapidly without tools. The fluid-bed processor, due to its special filter concept with ergonomic access by means of a hinged expansion chamber, comes in an extremely low built-in height, which makes it suitable to fit under ceiling heights as low as 3100 mm without sacrificing the process capabilities of the fluid-bed processor.
This RC granulation line is highly flexible, and it also includes peripherals like wet mill, dry mill, vacuum discharge unit and optionally a lifting column for carrying both the discharge unit and the dry mill. The control system of the granulation line is central, and all its components are connected.
DIOSNA is the partner for processing plants for the production of solids for the pharmaceutical, food and cosmetic industries. The product portfolio includes mixers, granulators, dryers, and coating systems for R&D and production scale.
Countless customers worldwide have been appreciating the quality and performance of DIOSNA systems for over 130 years. Thousands of references and machines that have been working reliably for decades prove the success of our corporate philosophy: To be a dependable and competent partner for our customers over the entire life cycle of the machines and systems we deliver - in product development, process optimization, project management and after sales service.
Drug developers know that the odds of anyone compound demonstrating safety and efficacy for a disease and its affected populations are low. How can drug developers improve these odds and increase the efficiency and effectiveness of drug development? One useful tool is model-informed drug...
High-speed filling of liquid pharmaceuticals is a timely topic as we find ourselves in the midst of the global SARS-CoV-2 pandemic. Learn about the exciting ultra-high speed capabilities realized with Syntegon's filling lines here.
The commissioning of a cleanroom is a complex and crucial process with many stages that start after the rooms are designed and built. The ultimate goal of cleanroom commissioning is to confirm that the controlled space will have a robust, clean and safe environment for the processing of drug...