Evaluation for stability data

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

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Q1E Evaluation for stability data, Feb. 6, 2003. 

Energetic data, calculated at the DPT level in Table 11.1 - (Diudea and Nagy 2011a, b) show a good stability of the start and intermediate structures. Limited cubic domains of the D5 networks have also been evaluated for stability, data proving a pertinent stability of the (yet) hypothetical D5 diamond. 

Testing of Drug Substances and Drug Products Q1E Evaluation for Stability Data... 

ICH QIE, Evaluation for Stability Data recommends the ways and means to use stability data generated in accordance with the principles in the ICH guideline Q1A(R2) Stability Testing of New Drug Substances and Products A summary of ICH QIE is described below. 

For an attribute that is known to decrease over time, the lower one-sided 95% confidence limit should be compared to the acceptance criterion. For an attribute that is known to increase over time, the upper one-sided 95% confidence limit should be compared to the acceptance criterion. If the attribute increases or decreases over time or whose direction of change is not known, a two-sided 95 % confidence limit should be calculated and compared to the upper and lower acceptance criteria. Other examples of statistical approaches to the analysis of stability data from single or multifactor, full or reduced design studies can be found in ICH QIE Evaluation for Stability Data ... 

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

Guidance for evaluation of stability data is provided in ICH QIE Evaluation of Stability Data. The sections relevant to. solid dosage forms are described below. 

Regression analysis is considered an appropriate approach to evaluating the stability data for a quantitative attribute and establishing a shelf life. The nature of the relationship between an attribute and time will determine whether data should be transformed for linear regression analysis. The relationship can be represented by a linear or nonlinear function on an arithmetic or logarithmic scale. In some cases, a nonlinear regression can better reflect the true relationship. An appropriate approach to shelf life estimation is to analyze a quantitative attribute (e.g., assay, degradation products) by... 

In each case the report includes a summary of the design given in the protocol, the tests and procedures used in the studies with the appropriate limits for evaluation, the stability data tables with the necessary batch documentation, and finally the discussion of results and conclusions. 

Guidelines for Evaluation of Stability Data in Retest Periods... 

A flow diagram on how to analyze and evaluate longterm stability data for appropriate quantitative test attributes from a study with a multifactor full or reduced design is provided in Appendix A. The statistical method used for data analysis should consider the stability study design to provide a valid statistical inference for the estimated retest period or shelf fife. 

QIE Evaluation of Stability Data Page 2 Factors that can cause an apparent lack of mass balance should be considered, including, for example, the mechanisms of degradation and the stability-indicating capability and inherent variability of the analytical procedures... 

Abstract This chapter discusses the evaluation of stability data. It follows the stability study information from the point that raw data is generated in the lab, calculations are performed to give test results, and test results are entered in the stability summary sheets, until data is finally entered into a stability report for submission purposes. This chapter also includes a summary of data evaluation addressed in ICH QIE and a discussion of Out-of-Speciflcation (OOS) and Out-of-Trend... 

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. 

Wessels P, Holz M, Erni F, Krummen K, and Ogorka J (1997) Statistical evaluation of stability data of pharmaceutical products for specification setting. Drug... 

The scope of ICH QIE addresses the evaluation of stability data that should be submitted in registration applications for new molecular entities and their associated drug products. A systematic approach should be adopted in the presentation and evaluation of the stability information. The stability information should include, as appropriate, results from physical, chemical, biological, and microbiological tests. Mass balance should be assessed and the factors that can cause an apparent lack of mass balance the mechanism of degradation and the stability-indicating capability and inherent variability of the analytical procedures. 

Incidentally, isocyanides are polar (for CNC H, the dipole moment is 3.44 D) and they are good bases (vs. BRj, H+), whereas CO is a poor base hence isocyanides can function as ligands in metal complexes where carbon monoxide does not. The scarcity of low-valent isocyanide complexes is less easily explained, however. Arguments involving 77-acceptor capacity are quite inappropriate. More data on low-valent species, and evaluations of stabilities, modes of decomposition, and reactions are desirable. 

Are the equilibrium constants for the important reactions in the thermodynamic dataset sufficiently accurate The collection of thermodynamic data is subject to error in the experiment, chemical analysis, and interpretation of the experimental results. Error margins, however, are seldom reported and never seem to appear in data compilations. Compiled data, furthermore, have generally been extrapolated from the temperature of measurement to that of interest (e.g., Helgeson, 1969). The stabilities of many aqueous species have been determined only at room temperature, for example, and mineral solubilities many times are measured at high temperatures where reactions approach equilibrium most rapidly. Evaluating the stabilities and sometimes even the stoichiometries of complex species is especially difficult and prone to inaccuracy. 

Vital signs may be measured with the patient in a supine, seated, and/or erect position. Both supine and erect positions are usually used if orthostatic changes are being evaluated. The need for such data will depend on the situation, but the position of the patients for this examination, as well as the period of time desired for stabilization, should be noted in the protocol. 

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