(1997; 248 pages) [French]
2.3 Technical elements
2.3.1 Quality specifications
Quality specifications comprise a set of properly selected standards with associated methods of analysis that may be used to assess the integrity of drugs (including dosage forms) and starting materials. Adequate specifications for a particular drug in its dosage forms for identity, purity, strength, performance and other characteristics are necessary to assure that all batches of the drug are of uniform quality. Quality can then be achieved by strict adherence to the specifications.
In the course of drug evaluation for registration, tentative dosage form specifications are developed when clinical studies have proceeded sufficiently to suggest that the dosage form is an acceptable one. They are reviewed as further experience in drug manufacture is gained. This question was discussed in Annex 5 of the twenty-fifth report of the Expert Committee on Specifications for Pharmaceutical Preparations (2).
Quality specifications may be either public or undisclosed in nature. The public specifications are usually contained in a pharmacopoeial monograph and are stated in terms that permit objective evaluation of product quality, not only by the manufacturer but by other interested parties also.
A pharmacopoeia normally includes the general methodology of testing, monographs on pharmaceutical raw materials, including active and inactive ingredients of pharmaceutical products, and in many cases monographs on dosage forms. A number of national pharmacopoeias are kept up to date by periodic revision. Pharmacopoeias may also be issued through the joint effort of a group of countries. The European Pharmacopoeia and the Compendium Medicamentorum are recent examples of such endeavours. The International Pharmacopoeia is issued by the World Health Organization; volume 1 of the third edition (8) was published in 1979. Plurinational pharmacopoeias and the International Pharmacopoeia serve to make more uniform test methodology and specifications for a particular product.
There are many specifications that either are contained in an application for an authorization or registration or exist as the manufacturer’s own specifications, which are not generally subject to public disclosure. Interested parties must therefore depend on the licensing authorities or the manufacturer for assurance that these specifications are adequate and are being met. Such assurance is mentioned in the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (4) (see section 4.2.1) through its provision concerning batch certificates to be provided by the manufacturer.
Analytical criteria for judging drug quality, which relate to the identity, purity and strength of drugs and to the performance of dosage forms, the selection of such criteria for pharmacopoeial monographs and for manufacturer’s specifications, and the relation between these two sets of quality requirements were reviewed in Annex 1 of the twenty-sixth report of the WHO Expert Committee on Specifications for Pharmaceutical Preparations (1).
The selection of methods and procedures used in specifications must be based on their utility for the purpose of quality assurance of pharmaceuticals, and progress in the development of new analytical tools requires a periodic review of the methodology. In establishing specifications full account must also be taken of various technical and economic constraints.
2.3.2 Basic tests
Simplified tests (basic tests) may serve in specific circumstances for verifying the identity of a drug and ascertaining the absence of gross degradation or contamination. They may be specially useful in situations in which well-equipped laboratories do not exist and in which full examination of drug quality according to procedures requiring special skills and equipment is not feasible. When a product fails the basic tests, it should not be used until its quality is established by a full analytical examination. Various aspects of the problem of the development and application of such tests are discussed in Annex 2 of the twenty-sixth report of the WHO Expert Committee on Specifications for Pharmaceutical Preparations (1).
2.3.3 Requirements for good manufacturing practices
The quality of pharmaceutical products depends on the correct performance of all manufacturing operations and must be built in from the beginning of the manufacturing process. The principles for quality control procedures that should be applied to drug manufacturing practices are designated “Good practices in the manufacture and quality control of drugs” (4) (see section 2.2.2). These principles are general guides which, whenever necessary, may be adapted to meet national needs, provided the established standards of drug quality are still achieved. Manufacturing establishments with a limited product line need only utilize the relevant parts of the requirements.
The requirements for good manufacturing practice indicate that the documents relating to manufacturing procedures should contain, among other necessary information, the data concerning each starting material, as well as detailed instructions for and precautions to be taken in the manufacture of the drug. If modifications due to changes in the equipment for processing or to the use of alternative types of ingredients are introduced, their influence on the quality, including the performance, of dosage forms has to be adequately evaluated.