(705b) Scientific Considerations and Regulatory Challenges for Low Dose Drug Manufacturing Process Monitoring and Control

Authors: 
Wu, H., FDA/CDER
Wu, S., FDA CDER OPQ
Sowrirajan, K., FDA/CDER
Cruz, C. N., U.S. Food and Drug Administration
For solid dosage form manufacturing, assay and content uniformity (CU) are two critical quality attributes (CQAs) of drug product that are impacted by powder blending, blend transferring, and tableting or capsule filling. Clinically, assay, CU, and dissolution together ensure that patients receive the strength claimed in the label and thus impact clinical efficacy and safety. The criticality of the powder blending operation and its outcome (e.g., blend uniformity (BU) and blend assay) increases for low dose drugs where the amount of active is very small in comparison to the amount of excipients. Therefore, low dose drug manufacturing process monitoring and control are uniquely challenging.

In this presentation, we will discuss scientific case studies excerpted from research studies and drug applications, challenges and opportunities, along with considerations for low dose drug manufacturing process monitoring and control. Specific attention will be paid to the easily overlooked or under-reported areas such as: 1) risk-based PAT monitoring interface location considerations for both batch processing and continuous manufacturing; 2) evaluation of engineering process scale-up criteria as applied to powder blending process; 3) sampling and analytical methods. Our discussion will illustrate a holistic approach supported by solid scientific understanding for low dose drug manufacture.