In view of the many advantages, continuous processes are also becoming more and more popular in pharmaceutical production. For the production of solid dosage forms Lödige Process Technology offers the pharmaceutical industry machines and systems that combine the continuous process with the proven GMP standards.
The highest standards of quality and safety are a matter of course in pharmaceutical production. This is not least due to the internationally applicable GMP guidelines (Good Manufacturing Practice). In this respect, it is understandable that technical innovations are slow to catch on in this particularly demanding environment.
The “Process Analytical Technology” (PAT) initiative launched by the US Food and Drug Administration (FDA) is counteracting this: under the motto “Quality by Design”, it places a higher value on the exact knowledge of the individual processes and thus enables significantly more flexibility in the production of medicinal products. Since then, the original scepticism towards continuous production processes in the pharmaceutical industry has also given way to a great deal of interest – and rightly so, because continuous processing offers numerous advantages.
Advantages of continuous processes
The economic production of large quantities of products has thus far been considered the main argument for continuous processes. However, there are a number of other advantages that are even more crucial in the pharmaceutical industry and make it interesting to use even for smaller throughputs:
- Consistent product quality: Once set, continuous processing ensures consistent product quality throughout the production period.
- Production quantity can be determined over runtime: Once the desired production quantity has been reached, the process is terminated.
- Smaller machines: As there is less mixing material in the machine at any given time than when processing in batches, containers and drives can be designed to be much smaller with the same output.
- Less manual handling of products: Continuously operating machines can be integrated into comprehensive systems with automatic feeding, which eliminates many work steps. This reduces the risk of unintentional contamination.
- Occupational safety: For the same reasons, staff are less exposed to the product, making it easier to ensure occupational safety.
- Fewer staff required: Equally, fewer workers are needed.
- Less cleaning work: In batch operation, the cleaning intervals are short. In extreme cases, cleaning needs to be done after each batch. With continuous processes, on the other hand, the system only needs to be cleaned when the product is changed.
- Lower production costs: In summary, continuous processes enable reduced production costs with at least identical product quality compared to batch operation.
Continuous mixing and related processes
In general, all continuous machines and systems can also be used in the pharmaceutical industry, provided they meet all GMP requirements. This means, for example: They must meet the specific requirements of a hygienic design. Technical and clean room areas must be arranged separated (black/white separation). An integrated cleaning function (Wash-in-Place, WIP) and quick access for easy inspection must also be ensured.
As a specialised supplier of machines for mixing, granulating and drying solids, Lödige has also been implementing continuous solutions for many industries since the 1950s. Since then, the company has consistently developed its pharma-specific portfolio. Today, Lödige can continuously realise the complete process in tablet production – from the raw materials to the tabletable granulate and, with cooperation partners, even beyond.
Two basic manufacturing processes are available for this purpose:
- With direct compression, the necessary components are provided for the process by container, big bag or, for small components, via bag dumps. Then, according to the specific composition, these are first fed via differential dosing scales to a continuous mixer, which produces a homogeneous mixture, and then pass to a tablet press. Depending on the product properties, other components can also be used between the mixer and the tablet press, such as a roller compactor.
- In continuous moist granulation, the first two steps are identical to direct compression. However, after the mixing step, the product needs to be moistened, granulated and then the granulate dried before it is processed into tablets again in a tablet press.
For both production processes, different measuring points (PAT) are installed in all process steps to ensure that the quality of the product can be controlled and documented at any point in the process.
Beyond the pure machine technology, the control and regulation software plays a key role in continuous production: During operation, it compares all measured parameters with the set values in order to be able to intervene and readjust accordingly in the event of any deviations. In addition, this ensures that in the event of a deviation that does not conform to specifications, the system stops and does not restart until the fault has been rectified.
In addition to the control of the actual production process, the control system must ensure the complete tracking of the tablets produced. For this, the huge amounts of data have to be processed and stored accordingly.
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