STATISTICAL EVALUATION OF STABILITY DATA OF PHARMACEUTICAL PRODUCTS FOR SPECIFICATION SETTING

Recent experience has shown that the regulatory authorities try to nar row specifications for a new drug product closely around stability dat a that have been generated in the course of registration stability tes ting. This should ensure that the quality of the marketed product is p roduced within tight limits, very similar to the quality which is regi stered. A strategy is proposed to set scientifically based, statistica lly justified specifications. The long-term stability data available a t the time point of registration application are extrapolated to a tar get shelf life (usually 36 months) of the new pharmaceutical product b y linear regression. Batch-to-batch heterogeneity is tested as prescri bed by the International Conference on Harmonization (ICH) guideline o n stability testing of new drug substances and drug products. The data of different batches are combined in appropriate statistical models f or further evaluation. The one-sided 99% confidence limit for individu als is used for the determination of release and shelf life specificat ions. Special attention is given to power calculations by which patien ts' risk of receiving material which does not fulfill the requirements can be controlled.