The Pharma industry is shifting from batch to continuous manufacturing, stimulated by Pharma 4.0, for many beneficial reasons e.g., faster production with higher flexibility, modular manufacturing, better monitoring and control over individual processes, more consistence product quality, reducing production cost, reducing footprints, etc. Adapting continuous manufacturing requires the redesign of processing steps. Powder processing steps, such as feeding and blending, are critical for continuous pharmaceutical manufacturing. For example, within a continuous powder-to-tablet manufacturing setup, feeders deliver the formulation components to the downstream process and finally to the final drug products. Therefore, any variation or inconsistency in feeding can impact the quality of final drug products. For the design of feeders as well as the downstream processes, the powder properties should be known, including the particle size distribution, flowability, compressibility, electrostatic chargeability, and tendency to segregate. Typically, these properties are measured for the raw materials once and the impact of batch to batch variability of raw materials is not considered as it is not yet well known and understood. This is problematic, as the inconsistency of raw materials can affect the consistency and quality of the final drug products.
Batch to batch variation of raw materials is one of the challenges in continuous manufacturing, as the production is uninterrupted, and the unit operations are connected. It is also highlighted by recently published ICH quality guideline Q13 on continuous manufacturing that the impact of raw material attributes and their variability on continuous processing should be assessed. In our presentation, we show a case study investigating the impact of material variability on feeding performance in different continuous manufacturing feeder setups. A spray dried lactose was selected as a reference material, as it is one of the most widely used filler binders for direct compression of tablets (it can make up to 70% of the tablet content). Over 200 batches, to our best knowledge for the first time, were evaluated regarding the impact of batch to batch variability upon feeding performance in volumetric mode. We investigated how minor variations of a free-flowing spray dried lactose can impact the feeding performance in two tested different feeder setups. Our results show that for an optimized feeder setup with 22 mm double concave screws rotating at 342 rpm, the batch-to-batch variation was negligible compared to the natural feeding variability. However, for a stretched feeder setup with 11 mm double concave screws rotating at 514 rpm, variability in material properties introduces additional variation. In conclusion, both feeder setup and excipient variability are factors to consider when optimizing feeding consistency in continuous pharmaceutical manufacturing.
Learning Objectives:
Have a better understanding of the natural batch to batch variability of raw materials.
Link the raw material variation to their process. Which variation do they have in the raw material, and what does the variation mean for their process.
Assess the risk of using raw material (with its natural variation) on process robustness and consistency of the final product.
How to derisk using excipients in continuous manufacturing processes