Extension of the International Conference on Harmonization Tripartite Guideline for Stability Testing of New Drug Substances and Products to Countries of Climatic Zones III and IV

Abstract

The International Conference on Harmonization (ICH) Tripartite Guideline "Stability Testing of New Drug Substances and Products" sets out the stability testing requirements for a registration application within the three areas of the European Union, Japan, and the United States. These areas are assigned to climatic zone II with the storage condition of 25 degrees C/60% RH. This paper describes the adjustments that are necessary to extend the guideline to countries of climatic zones III and IV. At first storage conditions were derived with 30 degrees C/35% RH for climatic zone III and 30 degrees C/70% RH for climatic zone IV. Both conditions contain a margin of safety compared to calculated and measured data in warehouses. Furthermore, they cover the extreme temperatures above 30 and 40 degrees C which may arise in these climatic zones. Six months at 40 degrees C/75% RH was fixed as storage condition for accelerated testing to assess organoleptic and physicochemical test criteria and to make predictions for chemical stability. The predictive factor is 3.3 for 30 degrees C (6 months at 40 degrees C corresponds to 20 months at 30 degrees C). Extreme temperatures which may arise during shipment are covered by the results of stress investigations (e.g., 3 months at 50 degrees C). The next adjustment is necessary for the selection of the packaging containers. They must reflect the requirements for solid, semisolid, and liquid dosage forms caused by the two storage conditions. In the evaluation the temperature difference of 10 degrees C (40-30 degrees C) instead of 15 degrees C has to be considered, which limits the preliminary shelf lives in critical cases to 18 months instead of 24 months. Finally, statement/labeling must reflect the storage conditions. All of the other basic principles for the drug substances and drug products, such as selection and number of batches, test criteria, test procedures, specifications, testing frequency, and storage period can be applied without any change.

Definição de shelf life para produtos químicos: a importância de um guia de estabilidade específico para o segmento

“…No intuito de reduzir o montante de testes de estabilidade, principalmente os de longa duração, Futscher e Schumacher, em 1972, 16 e Grimm, em 1986 17 e em 1998, 4 definiram quatro condições para testes de longa duração que simulam condições climáticas dos mercados alvo categorizados em apenas quatro zonas climáticas diferentes. 18 Esta delimitação do mundo em quatro zonas climáticas, especificada na Tabela 2, de acordo com critérios de temperatura cinética média e umidade relativa, possui particular relevância em estudos de estabilidade e definição de shelf life e, por isso mesmo, vem sendo amplamente discutida por países que contestam os dados padronizados a eles atribuídos.…”

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“…Storage period -It generally extend from minimum of 3 or 6 months in accelerated and stress testing and up to 12, 18, or 60 months in ongoing or follow-up stability testing 7. Testing frequency -It should be sufficient to establish the stability profile of the drug [15] Test schedules for different types of stability testing are shown in Table 6. 8.…”

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“…Analytical study of mugdha cream [9,10] The analytical study of cream was including viscosity, rheological studies, type of emulsion, and primary skin irritation test.…”