Stability testing conditions

The Secretariat reminded the Committee that the WHO guidelines had been revised in the light of harmonization efforts in collaboration with ICH. Subsequently focus had been placed within regional harmonization initiatives on the recommendations for hot and humid conditions (referred to as Zone IV). After extensive discussion the Committee reached consensus that the WHO stability guidelines be amended to reflect conditions for Zone IV as follows  

It was agreed that each individual Member State within the former Zone IV would need to indicate whether its territory should be classified as Zone IVa or IVb. 

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Specific stability test condition ) and contents per package in all charts generated. 

The temperature/humidity conditions used may be more severe than the typical accelerated stability testing conditions in order to generate potential degradation products in a reasonable time. The typical forced degradation conditions include thermolytic, hydrolytic, oxidative, photolytic (in excess of ICH conditions), high pH (alkaline conditions), and low pH (acidic conditions). Outlined in Table 9-25 and Table 9-26 are some solid-state and solution forced degradation studies, respectively, that could be conducted. In the following... 

There are generally two types of stability studies conducted 1) regular and 2) accelerated. In the case of accelerated stability study, the product is stored under elevated temperature and relative humidity (RH) conditions to force or expedite its degradation pathway and assess the changes. The stability testing conditions depend on the anticipated market environment. An example of a recommended protocol is provided in Table 1. 

Figure 2. SEM images of catalysts after stability test, (a) 0.5% Pd/MgO, (b) 0.5%Pd/Nio,2Mgo.sO. (c) Nio.2Mgo.8O, (d) 0.1%Pd/Nio,2MgosO. Stability test conditions are described in Figure 1.

Thus, it is no longer acceptable for the formulator to delay this compatibility testing until later in the development programme. The key message is for the formulator to test early and ensure equivalence of the whole product throughout the development cycle. Leachables are specifically mentioned data on their identity and concentration in the product and placebo are required through the shelf life and also under accelerated stability test conditions. Information should be submitted on source, chemical composition and physical dimensions of the container closure system, together with control and routine extraction tests. Acceptance criteria are also required. 

If the dimensionless parameter h is equal to t>l/2a > 2, then the stability test condition can be shown in the form of... 

A major step forward toward the definition of adequate stability testing conditions based on good science was made by introducing the Mean Kinetic Temperature... 

By running stability tests at these artificial conditions, a safety margin is built in by default. This fact has to be kept in mind when stability-testing conditions are being established and additional safety margins are regarded as necessary. 

Revert to 30°C/70%RH as the long-term stability testing condition for Zone IV as it is likely that considerable data are already available. This might serve as a potential platform for future harmonization between ICH and WHO. 

ASEAN member countries are establishing a common market in order to facilitate a free movement of goods within the borders of the association [20]. As a consequence, a product which is marketed in a less hot and humid ASEAN member state could easily be distributed to another country which is very hot and humid. Therefore, the hottest and most humid part of the common market determines the stability testing condition. 

For pharmaceutical products in semi-permeable packaging material, the standard long-term stability testing condition has now been moved to 30°C/75% RH. 

Calculation of Long-Term Stability Test Conditions... 

The climate is mainly Mediterranean or hot and dry in deserts, and in between arid (steppe). The Mediterranean climate is covered by the standard long-term stability testing condition of 25°C/60% RH, while for the hot and dry places additional conditions should be deflned, in particular for populated areas. For details see Table 4.15. 

As a result of the evaluation of the climatic condition and a risk assessment, an appropriate long-term stability testing condition is proposed for each selected country (see Table 4.17). 

Table 4.17 Climatic zones assigned and recommended long-term stability testing conditions for...

The hottest and most humid climatic zone has been selected to establish the adequate stability testing condition for a particular country. 

Table 4.24 Typical schedule to support global stability testing conditions...

Giimm W. 1986. Storage conditions for stability testing (Part 2). Drugs Made Ger 29 39-47. Zahn M, et al. 2006. A risk-based approach to establish stability testing conditions for tropical countries. J Pharm Sci 95 946-965. Erratum 2007 J Pharm sci 96 2177 Kottek M, et al. 2006. World map of Koppen-Geiger climate classification updated. Meteorol. 

The oil is high in linoleic acid and contains 2-3% conjugated 18 2(Bemise a/., 1978 Vasconcelloset al., 1981 Vasconcellos and Berry, 1982). It has been fed to rats and to chickens without ill effects (Vasconcellos etal, 1981 Khoury et al, 1982). Laboratory-refined oil gave a peroxide value of 100 after 4.9 h under Active Oxygen Method (AOM) stability test conditions (Vasconcellos etal, 1982). 

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