Evaluating the Performance of the ICH Guidelines for Shelf Life Estimation

Abstract

The goal of shelf life estimation is to determine the storage time during which the entire product meets specification with acceptably high probability. The estimated shelf life should be “applicable to all future batches” (ICH Q1E, International Conference on Harmonization, 2003b). There is compelling evidence of issues with the International Conference on Harmonization (ICH) guidelines for shelf life estimation. Issues include fixed batch effects, poolability tests, and confidence intervals for the mean. Two conclusions from evaluating the ICH procedure are that batch effects should be random and that focus should be on a quantile. A procedure is needed that combines random batches with the ICH objective of estimating the minimum batch shelf life.

Key Words:

• Batch shelf lives
• ICH guidelines
• Linear mixed model
• Shelf life

ACKNOWLEDGMENTS

Funding for this research was provided by the Product Quality Research Institute (PQRI) through the PQRI Stability Shelf Life Working Group. PQRI, located in Arlington, VA, is a nonprofit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The authors thank all the members of the PQRI Stability Shelf Life Working Group for providing resources, guidance, ideas, and advice that greatly contributed to this research. This research was presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Statistics for Michelle Quinlan, June 2010.