Stability data evaluation

The stability data evaluation for drug substance or drug product intended for storage at room temperature should include evaluation of any significant change at... 

The details of the assessment of stability data are under intense discussion within the scientific community. A majority of laboratories evaluate data with acceptance criteria relative to the nominal concentration of the spiked sample. The rationale for this is that it is not feasible to introduce more stringent criteria for stability evaluations than that of the assay acceptance criterion. Another common approach is to compare data against a baseline concentration (or day zero concentration) of a bulk preparation of stability samples established by repeated analysis, either during the accuracy and precision evaluations, or by other means. This evaluation then eliminates any systematic errors that may have occurred in the preparation of the stability samples. A more statistically acceptable method of stability data evaluations would be to use confidence intervals or perform trend analysis on the data [24]. In this case, when the observed concentration or response of the stability sample is beyond the lower confidence interval (as set a priori), the data indicate a lack of analyte stability under the conditions evaluated. 

The basic concepts of stability data evaluation are the same for single- vs. multifactor studies and for full- vs. reduced-design studies. Data evaluation from the formal stability studies and, as appropriate, supporting data should be used to determine the critical quality attributes likely to influence the quality and performance of the drug substance or product. Each attribute should be assessed separately and an overall assessment made of the findings for the purpose of proposing a retest period or shelf life. The retest period or shelf life proposed should not exceed that predicted for any single attribute. 

This chapter describes the data evaluation that is to be performed from the time that data are generated until they are reported in a regulatory submission. Eigure 13.1 provides a flow diagram for stability data evaluation. 

Stability data evaluation must begin when raw data is generated in the laboratory. cGMPs require that drug products and drug substances must meet their... 

Chapter 13 discusses the collection and presentation of stability data. Evaluation of data (ICH QIE) is also discussed as well as Out-of-Specification (OOS) and Out-of-Trend (OOT) investigations. In addition, it also introduces the stability report and data trending. 

Example 4 A Stability/Runaway Hazard Assessment Report In Table 2.3, test data evaluating stability/runaway hazards of a material are presented. This table contains the relevant test data and evaluations in accordance with Section 2.1.5 (Test Strategies) and represents a good model for summary reports of such key information. 

ICH Harmonized Tripartite Guideline—Evaluation for Stability Data QIE, 2003. 

Evaluation of Stability Data and Shelf Life Determination... 

During the design of stability studies, bracketing and matrixing [10] may be used to achieve reduced testing while at the same time generating enough stability data for evaluation of shelf life. 

EVALUATION OF STABILITY DATA AND SHELF LIFE DETERMINATION... 

U.S. Food and Drug Administration (FDA) (2004), Guidance for industry, ICH Q1E, Evaluation of stability data, FDA, Rockville, MD. 

Q1E Evaluation of Stability Data Explains possible situations where extrapolation of retest periods/shelf lives beyond real-time data may be appropriate provides examples of statistical approaches to stability data analysis... 

Yoshioka S, Aso Y, Takeda Y. Statistical evaluation of accelerated stability data obtained at a single temperature. I. Effect of experimental errors in evaluation of stability data obtained. Chem Pharm Bull 1990 38 1757-1759. 

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