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
Close this folderStability of drug dosage forms1
View the document1. Introduction
View the document2. General considerations
Open this folder and view contents3. Responsibility of parties involved in the assurance of drug stability
View the document4. Use of terms
View the document5. Less stable drug substances
View the documentReferences
Open this folder and view contentsGuidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms1
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. General considerations

The most important factors that may influence the degree and rate of deterioration of drug products are the following:

(a) Environmental factors such as heat, moisture, light, oxygen and various other forms of physical stress and changes (for example, vibration or freezing).

(b) Product-related factors. These may include:

(i) the chemical and physical properties of the active drug substance and of the pharmaceutical aids (excipients) used (for example, the presence of certain impurities, the particular polymorphic or crystal form, the particle size and the possible presence of water or other solvents);

(ii) the dosage form and its composition;

(iii) the manufacturing process used (including environmental conditions and technological procedures);

(iv) the nature of the container or other packaging with which the product may be in direct contact or which may otherwise influence the stability.

All the above factors have to be considered when establishing the shelf-life of a product.

The stability of the finished product depends to a large degree upon the stability of the drug substance it contains. At the same time it should be noted that formulation and packaging may exert a positive or a negative influence on the stability of the active substance.1 In section 5 drug substances are listed that were found to be less stable under simulated tropical conditions. All other factors being equal, finished products containing these substances require particular attention from the stability viewpoint.

1 It follows that the stability of a product is producer-specific.

For each product the shelf-life has to be established on the basis of stability testing. For practical reasons of commerce and distribution, a stated shelf-life exceeding five years is not recommended. Shorter shelf-lives may be expected for numerous active ingredients, e.g. antibiotics and vitamins, or for some types of dosage form, e.g. certain aqueous solutions, emulsions or creams. Products developed and packaged for a temperate climate may not necessarily be suitable for distribution in tropical zones.

The stability overage2 is acceptable only in limited cases and on grounds of scientific and practical justification.

2 An excess of the active drug substance in a dosage form, added at the time of manufacture to compensate for the expected loss of potency during storage.

The use of time-expired drugs should be strongly discouraged. Only in exceptional cases, e.g. emergencies, should the use of such products be considered. The decision to utilize such products may be taken on a case-by-case basis by a responsible national health authority only, and then after careful weighing of all relevant factors by a competent professional. In such cases, samples of these products have to be retested against pharmacopoeial or similar standards by stability-indicating methods such as chromatography, attention also being paid to microbiological aspects. The economic loss and health hazards arising from the rejection of expired stock should be balanced against risks of impaired efficacy and safety. The availability of other appropriate medicines and/or the practicability of replenishing stocks should be taken into consideration. The eventual liability problems should be considered since the expiry date indicates the moment at which the manufacturer’s liability for the product may be relinquished. Whenever feasible, such a decision should be taken after consultation with the manufacturer as well as with independent experts. When a decision is taken to use time-expired material, a new expiry date, well defined and as limited as practicable, has to be established.

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