Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1
(1997; 248 pages) [French] View the PDF document
Table of Contents
Open this folder and view contentsIntroduction
Open this folder and view contents1. National drug regulation
Close this folder2. Product assessment and registration
View the documentGuidelines for the assessment of herbal medicines1,2
Open this folder and view contentsStability of drug dosage forms1
Close this folderGuidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms1
View the documentGeneral
View the documentDefinitions
View the document1. Stability testing
View the document2. Intended market
View the document3. Design of stability studies
View the document4. Analytical methods
View the document5. Stability report
View the document6. Shelf-life and recommended storage conditions
View the documentReferences
View the documentOfficial, international and national guidelines
View the documentAppendix 1. Survey on the stability of pharmaceutical preparations included in the WHO Model List of Essential Drugs: answer sheet
View the documentAppendix 2. Stability testing: summary sheet
Open this folder and view contentsMultisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability1
Open this folder and view contents3. Distribution
Open this folder and view contents4. The international pharmacopoeia and related activities
Open this folder and view contents5. Basic tests
Open this folder and view contents6. Laboratory services
Open this folder and view contents7. International trade in pharmaceuticals
Open this folder and view contents8. Counterfeit products
Open this folder and view contents9. Training
View the documentSelected WHO publications of related interest
View the documentBack cover
 

2. Intended market

The design of the stability testing programme should take into account the intended market and the climatic conditions in the area in which the drug products will be used.

Four climatic zones can be distinguished for the purpose of worldwide stability testing, as follows:

• Zone I: temperate.
• Zone II: subtropical, with possible high humidity.
• Zone III: hot/dry.
• Zone IV: hot/humid.

(See Schumacher P. Aktuelle Fragen zur Haltbarkeit von Arzneimitteln. [Current questions on drug stability.] Pharmazeutische Zeitung, 1974, 119:321-324.)

The mean climatic conditions, calculated data and derived storage conditions in these zones are summarized in Tables 2 and 3.

Table 2. Mean climatic conditions: measured data in the open air and in the storage room1

1 RH = relative humidity.

Climatic zone

Measured data
in the open air

Measured data
in the storage room

 

°C

% RH

°C

% RH

I

10.9

75

18.7

45

II

17.0

70

21.1

52

III

24.4

39

26.0

54

IV

26.5

77

28.4

70

Table 3. Mean climatic conditions: calculated data and derived storage conditions1

1 Based on: Grimm W. Storage conditions for stability testing in the EC, Japan and USA; the most important market for drug products. Drug development and industrial pharmacy, 1993, 19:2795-2830.

Climatic zone

Calculated data

Derived storage conditions
(for real-time studies)

 

°C2

°C MKT3

% RH4

°C

% RH

I

20.0

20.0

42

21

45

II

21.6

22.0

52

25

60

III

26.4

27.9

35

30

35

IV

26.7

27.4

76

30

70

2 Calculated temperatures are derived from measured temperatures, but all measured temperatures of less than 19 °C were set equal to 19 °C.

3 MKT = mean kinetic temperature (see p. 48).

4 RH = relative humidity.

Since there are only a few countries in zone I, the manufacturer would be well advised to base stability testing on the conditions in climatic zone II when it is intended to market products in temperate climates. For countries where certain regions are situated in zones III or IV, and also with a view to the global market, it is recommended that stability testing programmes should be based on the conditions corresponding to climatic zone IV.

In a stability study, the effect on the product in question of variations in temperature, time, humidity, light intensity and partial vapour pressure are investigated. The effective or mean kinetic temperature therefore reflects the actual situation better than the measured mean temperature; a product kept for 1 month at 20 °C and 1 month at 40 °C will differ from one kept for 2 months at 30 °C. Moreover, the storage conditions are often such that the temperature is higher than the average meteorological data for a country would indicate.

For some dosage forms, especially liquid and semi-solid ones, the study design may also need to include subzero temperatures, e.g. -10 to -20 °C (freezer), freeze - thaw cycles or temperatures in the range 2-8 °C (refrigerator). For certain preparations it may be important to observe the effects caused by exposure to light.

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