A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule...

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Materials Science

Background:

• Particle size analysis is crucial in pharmaceuticals, but defining measurement accuracy is problematic.
• Variations in measurement techniques, instruments, and calculations prevent a universal "true" particle size value.
• Current reliance on accuracy for particle size characterization is scientifically questionable.

Purpose of the Study:

• To propose a new framework for evaluating particle size measurements in the pharmaceutical industry.
• To introduce the concept of "appropriateness" as a replacement for "accuracy" in particle size analysis.
• To link particle size measurement validity to critical quality attributes (CQA) of the material.

Main Methods:

• Conceptual framework development for "appropriateness" in particle size measurement.
• Establishing the link between particle size measurement and CQAs.
• Assessing the role of precision in discriminating CQA variations.

Main Results:

• Accuracy is not a definable characteristic for real particles due to inherent measurement variability.
• "Appropriateness" of a measurement should be defined by its relevance to the material's CQAs.
• Demonstrating correlation between measured particle size and CQAs is essential for defining a critical material attribute.

Conclusions:

• Particle size measurement "appropriateness" should be prioritized over "accuracy" in pharmaceutical applications.
• Linking measurements to CQAs ensures the relevance and utility of particle size data.
• Methods must provide sufficient precision to detect meaningful variations related to CQAs.