(424b) Implementation of a Normalization Risk Assessment Tool to Link Design Space Inputs

Authors: 
Hou, D. S., Merck & Co.
MacPhail, N., Merck & Co.
Smith, E. J., Merck & Co.
Ho, J., Merck & Co.
Cleary, A., Merck & Co.


Risk analysis and assessment tools are a key component of Quality by Design (QbD) because they facilitate understanding, identifying, and documenting of risks affecting drug product quality attributes. As stated in the ICH Q8 guidelines, the ?design space? is where a process generates a product that meets all of it's critical quality attributes through a multidimensional combination and interaction of input variables and process parameters. The design space should be developed by addressing the risks identified in the risk analysis. There are several methods to prioritize the risk analysis to develop a mitigation strategy of the risks to bracket the desired design space.

Using a normalization tool, we have demonstrated a methodology to address the issue of sorting and prioritizing the risk analysis information. This tool enables standardization of the analysis of the risk assessment tool across development teams and projects. A case study for a high shear granulated product is presented to demonstrate how this tool can be used to identify key factors from the risk assessments and to drive the development work needed to support the definition of the design space.