I. General Framework :
- Stability of pharmaceutical products: Critical factor of quality
The stability of a pharmaceutical product is defined according to the ICH, as ” the ability of a drug to maintain its physical, chemical, microbiological and biopharmaceutical properties within specified limits during its shelf life.”
- Stability studies of pharmaceutical products:
Before being marketed and in order to grant the Marketing Authorization, a pharmaceutical product is subjected to stability assays under standardized and international conditions. This stability must be ensured throughout the validity period of the medicinal product. Guidelines have been recommended by the ICH and WHO, in order to test the variations of the quality of an active substance AP or a drug over the time, according to different environmental factors (Temperature, Humidity, Light). These studies will allow the pharmaceutical industry to define the storage conditions, to determine the period of validity of its products, and to guarantee patients pharmaceutical products of quality, efficacy, and safety.
II. The ICH et OMS guidelines
- The guideline ICH Q1A-Q1F
The ICH guideline of stability studies includes a set of 6 guidelines (Q1A-Q1F) detailing for each of them, more specific aspects. The main guideline is the Q1A (R2), detailing the stability studies to be conducted, when a new PA or a new specialty is subjected to the Marketing Authorization grant, in one of the tripartite regions of ICH (Europe, United States United and Japan). The main requirements recommended by the ICH guideline are the selection of batches, the type of sample packaging, the frequency of tests and the general storage conditions (temperature and relative humidity) to be evaluated.
- The WHO guidelines:
The WHO has drafted its own guideline « Stability testing of active pharmaceutical ingredients and finished pharmaceutical product » (2009). The recommended guidelines of WHO are almost identical to those of the ICH guidelines, except for a few differences such as batch selection and general storage conditions.
Annexe 1 of this guideline is the most important part, it summarizes for each WHO member country, the conditions to be applied during the long-term stability studies. Indeed, the WHO has defined 5 climatic zones:
- Zone I (Temperate climate; 21°C/45% RH),
- Zone II (Subtropical and Mediterranean Climate; 25°C/60% RH),
- Zone III (Hot and dry climate; 30°C/35% RH)
- Zone IVA (Hot and humid climate; 30°C/65% RH)
- Zone IVB (Hot and very humid climate; 30°C/75% RH).
Each zone corresponds to the conditions to be applied during long-term stability studies. Each member country is therefore classified in one of these zones according to two criteria: the average annual temperature measured in the open air and the annual average partial water vapor pressure.
II. Stability studies requirements in Africa:
In Africa, as examples Tunisia, Morocco, Algeria and the 8 member states of UEMOA (Benin; Burkina-Faso; Ivory Coast; Guinea-Bissau; Mali; Niger; Senegal et Togo), these countries apply ICH and WHO guidelines in stability studies associated with the registration and the marketing of pharmaceutical products. The Maghreb countries (Tunisia, Morocco, Algeria), belonging to WHO zone II, conduct their long-term stability studies at 25°C/60% RH, while UEMOA member states, except for Togo, belonging to the zone IVA apply 30°C/65±5% RH. Togo belongs to zone IVB and conducts its stability tests at 30°C/75% RH.
We note that the countries of North of Africa apply the same zone and requirement in terms of humidity and temperature as for the most European countries whereas, the other African countries apply zones where the temperature and humidity are higher; this is due to the different climatic conditions.
It is also essential for the registration of an imported product into these countries, to finalize the stability study during the proposed period of validity.
AREMA, own its experts’ team and local partners as well as its REMAREG regulatory intelligence platform, offers in-depth studies of the compliance of your documents with the stability requirements and other requirements of each of the designated country.