WHO Expert Committee on Specifications for Pharmaceutical Preparations - WHO Technical Report Series, No. 885 - Thirty-fifth Report
(1999; 168 pages) [Spanish] View the PDF document
Table of Contents
View the documentWHO Expert Committee on Specifications for Pharmaceutical Preparations
View the document1. Introduction
Open this folder and view contents2. The international pharmacopoeia and related issues
Open this folder and view contents3. International Chemical Reference Substances and Infrared Reference Spectra
Open this folder and view contents4. Quality control - national laboratories
Open this folder and view contents5. Good manufacturing practices
Open this folder and view contents6. Quality systems and inspection
Open this folder and view contents7. Other quality assurance topics
Open this folder and view contents8. Nomenclature and terminology
Open this folder and view contents9. Legal aspects of pharmaceuticals
Open this folder and view contents10. Regulatory issues
Open this folder and view contents11. Training activities
View the document12. Pharmaceuticals contaminated with diethylene glycol
View the documentAcknowledgements
View the documentReferences
View the documentAnnex 1. List of available International Chemical Reference Substances1
View the documentAnnex 2. List of available International Infrared Reference Spectra1
Close this folderAnnex 3. General guidelines for the establishment, maintenance and distribution of chemical reference substances
View the documentIntroduction
Close this folderPart A. Primary chemical reference substances
View the document1. Assessment of need for the establishment of chemical reference substances
View the document2. Obtaining source material
Open this folder and view contents3. Evaluation of chemical reference substances
Open this folder and view contents4. Chemical and physical methods used in evaluating chemical reference substances
View the document5. Assignment of content
Open this folder and view contents6. Handling and distribution of chemical reference substances
View the documentPart B. Secondary chemical reference substances
View the documentReferences
Open this folder and view contentsAnnex 4. Good manufacturing practices: authorized person - role, functions and training
Open this folder and view contentsAnnex 5. Good manufacturing practices: supplementary guidelines for the manufacture of pharmaceutical excipients
Open this folder and view contentsAnnex 6. Guidelines for inspection of drug distribution channels
View the documentAnnex 7. Good pharmacy practice in community and hospital pharmacy settings
Open this folder and view contentsAnnex 8. National drug regulatory legislation: guiding principles for small drug regulatory authorities
Open this folder and view contentsAnnex 9. Provisional guidelines for developing training programmes: inspection and examination of counterfeit pharmaceuticals
View the documentWorld Health Organization Technical Report Series
View the documentSelected WHO Publications of Related Interest
View the documentBack Cover
 

2. Obtaining source material

Source material of satisfactory quality can be selected from a batch (lot) of the substance originating from the normal production process, if the purity is acceptable. Further purification techniques may be needed to render the material acceptable for use as a chemical reference substance.

The purity requirements for a chemical reference substance depend upon its intended use. A chemical reference substance proposed for an identification test does not require meticulous purification, since the presence of a small percentage of impurities in the substance often has no noticeable effect on the test.

On the other hand, chemical reference substances that are to be used in assays should possess a high degree of purity. As a guiding principle, a purity of 99.5% or higher is desirable, calculated on the basis of the material in its anhydrous form or free of volatile substances. However, where the selectivity of the analytical procedure for which the chemical reference substance is required is low, such a degree of purity may not be necessary. In making a decision about the suitability of a chemical reference substance, the most important consideration is the influence of the impurity on the attribute measured in the assay when used in a non-specific assay procedure. Impurities with physicochemical characteristics similar to those of the main component will not impair the usefulness of a chemical reference substance, whereas even traces of impurities with significantly different properties may render a substance unsuitable as a chemical reference substance.

When source material to be used as a chemical reference substance is obtained from a supplier, the following should be supplied with the material:

• Certificate of analysis with complete information as to test methods employed, values found and number of replicates used, where applicable, and relevant spectra and/or chromatograms.

 

• Information on optimal storage conditions required for stability (temperature and humidity considerations).

• Results of any hygroscopicity study and/or statement of the hygroscopicity of the source material.

• Results of any accelerated stability studies.

• Identification of detected impurities (by preference), and/or specific information on the relative response factor as determined in compendial methods concerning the principal component, and/or the percentage mass of the impurity.

• Updated Material Safety Data Sheet outlining any health hazards associated with the material.

 

For new drug substances, manufacturers should be aware that elaboration of pharmacopoeial monographs will be needed and a batch of the new substance should be set aside to be used if necessary as the chemical reference substance. It is desirable for bodies that issue chemical reference substances to provide each other with a sample of the same batch of material, even if the substance will be employed for different test methods. This will require the exchange of information concerning the establishment process, supplier(s), availability and conditions of supply.

to previous section
to next section
 
 
The WHO Essential Medicines and Health Products Information Portal was designed and is maintained by Human Info NGO. Last updated: October 7, 2014