Summary
The Food and Drug Administration (FDA) addresses testing for foreign particles in inhalational drug products. A Quality by Design (QbD) approach based on IPAC-RS (International Pharmaceutical Aerosol Consortium on Regulation and Science) recommendations was used to gain a good understanding of particulate contamination over our entire inhaler production process. The number of foreign particles in several drug substance batches before and after a change in manufacturing was enumerated by light obscuration. This was done in order to monitor potential influences on foreign particulate quality and for being in a position to take measures before receiving critical findings in the drug product. Therefore, drug substance was weighed into specially cleaned  laboratory bottles and dissolved in a water/acetonitrile solvent. The results revealed that the drug substance contained approximately four times as many foreign particles after the change in production when compared to those before the change. Based on these results, we decided to implement an additional filtration step to the production process of the drug substance. As a result, the amount of foreign particles in the drug substance batches dropped to their previous levels. This proactive QbD approach provided us with an effective tool to not only prevent a negative impact from foreign particles on the drug product quality, but to also ensure patient safety.