Shelf-life is always determined in relation to storage conditions. If batches of a product have different stability profiles, the shelf-life proposed should be based on the stability of the least stable, unless there are justifiable reasons for doing otherwise.
The results of stability studies, covering the physical, chemical, biological, microbiological and biopharmaceutical quality characteristics of the dosage form, as necessary, are evaluated with the objective of establishing a tentative shelf-life. Statistical methods are often used for the interpretation of these results. Some extrapolation of real-time data beyond the observed range, when accelerated studies support this, is acceptable.
A tentative shelf-life of 24 months may be established provided the following conditions are satisfied:
! the active ingredient is known to be stable (not easily degradable);
! stability studies as outlined in section 3.2 have been performed and no significant changes have been observed;
! supporting data indicate that similar formulations have been assigned a shelf-life of 24 months or more;
! the manufacturer will continue to conduct real-time studies until the proposed shelf-life has been covered, and the results obtained will be submitted to the registration authority.
Products containing less stable active ingredients and formulations not suitable for experimental studies on storage at elevated temperature (e.g. suppositories) will need more extensive real-time stability studies. The proposed shelf-life should then not exceed twice the period covered by the real-time studies.
After the stability of the product has been evaluated, one of the following recommendations as to storage conditions can be prominently indicated on the label:
! store under normal storage conditions;2
2 This statement may not always be required for products intended for areas with a temperate climate.
! store between 2 and 8°C (under refrigeration, no freezing);
! store below 8°C (under refrigeration);
! store between -5 and -0°C (in a freezer);
! store below -18°C (in a deep freezer).
Normal storage conditions have been defined by WHO (3) as: “storage in dry, well-ventilated premises at temperatures of 15-25°C or, depending on climatic conditions, up to 30°C. Extraneous odours, contamination, and intense light have to be excluded.”
These conditions may not always be met, bearing in mind the actual situation in certain countries. “Normal conditions” may then be defined at the national level. Recommended storage conditions must be determined in the light of the conditions prevailing within the country of designated use.
General precautionary statements, such as “protect from light” and/or “store in a dry place”, may be included, but should not be used to conceal stability problems.
If applicable, recommendations should also be made as to the utilization period and storage conditions after opening and dilution or reconstitution of a solution, e.g. an antibiotic injection supplied as a powder for reconstitution.