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
Open this folder and view contents2. Product assessment and registration
Open this folder and view contents3. Distribution
Close this folder4. The international pharmacopoeia and related activities
View the documentGuidance for those preparing or commenting on monographs for preparations to be included in The international pharmacopoeia1
View the documentValidation of analytical procedures used in the examination of pharmaceutical materials1
Close this folderGeneral guidelines for the establishment, maintenance, and distribution of chemical reference substances1
View the document1. Criteria for determining the need for the establishment of chemical reference substances
View the document2. Evaluation of reference substances
Open this folder and view contents3. Chemical and physical methods used in evaluating reference substances
Close this folder4. Handling and distribution of reference substances
View the document4.1 Packing and storage
View the document4.2 Stability and periodic re-evaluation
View the document4.3 Information to be supplied with reference substances
View the document4.4 Expiry of reference substances
View the document4.5 Distribution problems
View the document5. Reference materials calibrated against International Chemical Reference Substances
View the document6. Means of promoting effective exchange of information and ensuring cooperation between organizations establishing reference substances
View the documentGeneral recommendations for the preparation and use of infrared spectra in pharmaceutical analysis1
View the documentList of available International Chemical Reference Substances1
View the documentList of available International Infrared Reference Spectra1
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
4.1 Packing and storage

Containers for reference substances should afford protection from moisture, light, and oxygen. From the point of view of the stability of the substances, sealed glass ampoules are the best containers, but they suffer from certain disadvantages, notably the risk of contaminating the substance with glass particles when the ampoules are opened and the difficulty of re-closure. Sealed ampoules are therefore principally used for materials that must be kept in an oxygen-free atmosphere. Certain materials may require even more elaborate protection. Most chemical reference substances, however, are conveniently supplied in re-closable containers, which should be uniform in type and size to facilitate distribution. It is emphasized that the permeability of containers to moisture is an important factor in determining their suitability as containers for reference substances.

The packing of a batch of a reference substance into containers is a small-scale operation for which suitable equipment is not always available to the manufacturer of the substance. Therefore the packing of reference substances is usually undertaken by the authorities responsible for them.

Vibration spatulas and similar devices are available for dispensing substances on a small scale, but these should be used with caution because of the risk of segregation of particles of different size during the filling operation, which may lead to inhomogeneity. Screw-type feeders have also been constructed, but as yet are not commercially available, and so far the packing of reference substances has been done manually.

Several pharmaceutical reference substances have to be packed under nitrogen or in conditions of controlled humidity. The use of a glove-box is of great value in this connexion.

The various stages in packing reference substances should be controlled to avoid contamination of the sample, mislabelling of containers, and other factors that might result in an unsatisfactory reference substance.

Information about suitable storage conditions for reference substances can often be obtained from the manufacturer and should be requested routinely when a new reference substance is established. Theoretically the stability of the substances should be enhanced by keeping them at low temperatures but, for substances that contain water, storage below 0 °C may impair the stability. It should also be remembered that the relative humidity in normal refrigerators or cold-rooms may be high and, unless ampoules or other tightly closed containers are used, the intended improvement in stability by storage in such places may be more than offset by degradation due to the absorption of moisture. Storage at about + 5 °C with precautions to prevent such absorption has proved satisfactory for most chemical reference substances.

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