Stability schedules

Matrixing is a statistical design of a stability schedule so that only a fraction of the total number of samples are tested at any specified sampling point. At subsequent sampling points, different sets of samples from the total number are tested. 

Bracketing is the design of a stability schedule such that only samples on the extremes of certain design factors (e.g., strength, container size, and/or fill) are tested at all time points as in a full design. The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested. 

Matrixing is the design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations would be tested at a specified time point. At a subsequent time point, another subset of samples for all factor combinations would be tested. The design assumes that the stability of each subset of samples tested represents the stability of all samples at a given time point. The differences in the samples for the same drug product should be identified as, for example, covering different batches, different strengths, different sizes of the same container closure system, and possibly, in some cases, different container closure systems. 

A stability schedule is a series of stability test intervals at which time all or some of the stability tests will be run on a sample in the study. There is also a group of stability environments that are used to study the product. The combination of results obtained for the various test intervals and environmental conditions creates a stability profile. Data from this profile are used to define the recommended storage conditions for the product and the expiration date that can be supported by the data. A typical ICH stability schedule is found in Table 3. 

The design of a stability schedule so that at any time point only the samples on the extremes, for example of container size and/or dosage strengths, are tested. The design assumes that the stability of the intermediate condition samples are represented by those at the extremes. 

The methylated maleic acid adduct of phthalic anhydride, known as methyl nadic anhydride VI, is somewhat more useful. Heat distortion temperatures as high as 202°C have been quoted whilst cured systems, with bis-phenol epoxides, have very good heat stability as measured by weight loss over a period of time at elevated temperatures. The other advantage of this hardener is that it is a liquid easily incorporated into the resin. About 80 phr are used but curing cycles are rather long. A typical schedule is 16 hours at 120°C and 1 hour at 180°C. 

Many companies have developed or purchased computer software for the purpose of storing stability data for a large number of studies. Examples of commercially available systems are SLIM [147] and Stability System [148]. These systems can perform other functions as well, including work scheduling, preparation of summaries of selected or all studies in the system, tabulation of data for individual studies, label printing, statistical analysis and plotting, and search capabilities. Such systems should be validated to keep pace with current regulatory activity [149],... 

Patients should be encouraged to call their clinician if any problems or adverse events occur or if mood episodes occur between scheduled appointments rapidly identifying and correcting potential problems or making dosage adjustments is essential in achieving mood stabilization... 

Direct participation of the oceanographic research community will enable collection of matrix-based materials such as natural seawater or sediments in an efficient manner (for example, material collection could be combined with other scheduled research activities). Furthermore, the extensive analytical skills of the oceanographic research community can be harnessed to conduct the necessary testing for homogeneity, stability, and ultimately characterization of the proposed reference materials. At the same time, complete success requires the participation of reference material producers, who bring to the table extensive knowledge and experience in the preparation and stabilization of reference materials, and on occasion access to necessary facilities. 

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