(1997; 248 pages) [French]
1. Introduction and general considerations
In its twenty-sixth report (1), the WHO Expert Committee on Specifications for Pharmaceutical Preparations expressed the opinion that a comprehensive review of quality assurance in pharmaceutical supply systems might be of value for national programmes in the regulatory control of drugs1 and suggested that a suitable document should be prepared. The document should refer to international problems in the field of drug quality assurance and should include a consideration of related major WHO programmes. Since a lack of resources in certain areas might prevent the application of a comprehensive system of drug quality assurance, the Committee considered that the document should also recommend the course of action that might be taken to assure the quality of drugs being supplied under such conditions.
1 For the purposes of this document the definition of the term “drug” is identical to that given in “Good practices in the manufacture and quality control of drugs” (2, Annex 1): “Any substance or mixture of substances that is manufactured, sold, offered for sale, or represented for use in (1) the treatment, mitigation, prevention, or diagnosis of disease, an abnormal physical state, or the symptoms thereof in man or animal; or (2) the restoration, correction, or modification of organic functions in man or animal”.
The present document is an attempt to provide an outline of the elements involved in the development of national programmes concerned with the regulatory control of drug quality in pharmaceutical supply systems. It is intended primarily for use by the appropriate health authorities of Member States that are establishing or expanding their national drug quality assessment system.
It is necessary for each country to develop and maintain a drug quality assessment system, which should form an integral part of a national drug control system, designed to prevent the production, export, import, and distribution of ineffective, harmful or poor-quality drugs. Such a system must be based on appropriate legislation and be supervised by a suitably qualified and properly empowered authority, supported by inspection and laboratory services. Because of the wide variations that exist in pharmaceutical supply systems the organization of quality assessment and assurance has to be adapted to meet existing conditions. The subsequent sections of this document deal with various aspects of the system in depth, where this is appropriate. The subject-matter is, however, general in nature and the suggestions contained herein can be modified to meet local needs.
In the present document the term “quality” retains the meaning given to it in the twenty-second report of the WHO Expert Committee on Specifications for Pharmaceutical Preparations (3), which stated:
The suitability of drugs for their intended use is determined by (a) their efficacy weighed against safety to health according to label claim or as promoted or publicized and (b) their conformity to specifications regarding identity, strength, purity, and other characteristics.
Although these two groups of factors may be considered separately, they are, to some degree, interdependent.
In order to ensure that all batches of a given drug are equally efficacious and safe, it is essential to establish adequate specifications for the drug and its dosage forms. The desired quality can then be achieved by strict adherence to these specifications. In fact, once their efficacy and safety have been established, the quality of drugs available in commerce is judged by identifying them and by determining their strength, purity, and other characteristics.
It is considered that in the assessment of the quality of imported drugs, especially in countries that are heavily dependent on pharmaceutical products produced abroad, an increasing role should be played by the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (4), and the importing countries should make greater use of it. Further details concerning the operation of the scheme are given in section 4.2.1.
It is generally accepted that the manufacturer (including the firms packaging and labelling drugs) and the distributor (including importers, wholesalers, and retail and hospital pharmacists) should be responsible for the quality of the products they manufacture or distribute. Nevertheless, this does not release other persons involved in the process of distribution of pharmaceutical products, including physicians and other health personnel, from their obligation to be vigilant and to contribute, by virtue of their experience, to the assurance of drug quality.
An important facet of quality assurance concerns the packaging and storage of drugs. Adequate specifications for containers and directions for proper packaging and storage are indispensable to prevent or diminish the loss of quality caused by handling during shipment from the manufacturer or importer, storage at ports of entry, or movement in the chain of distribution through the wholesale distribution channels to the final outlet. Inadequate packaging and storage can lead to physical deterioration and chemical decomposition, resulting in a reduction in activity and, therefore, of therapeutic efficacy, as well as the formation of possibly harmful degradation products.
The factors which concern the efficacy and safety of drugs are mentioned in this document only to the extent to which they interface with the quality notion as expressed above. Pertinent elements of pre-marketing quality assessment are discussed in some detail in section 3. A discussion of the problems of bioavailability of drugs may be found in the report of a WHO Scientific Group on the Bio-availability of Drugs: Principles and Problems (5).
Aspects such as directions for use and other information given on labels or in package inserts, including storage requirements, may have quality implications but are not discussed. The present document is primarily concerned with the quality assessment of pharmaceutical products. Additional requirements specifically applicable to biological products (such as vaccines, toxoids and antisera) are given in a number of recommendations adopted by the WHO Expert Committee on Biological Standardization or other WHO expert groups. (See, for example, the report of a WHO Expert Group on Requirements for Biological Substances: Manufacturing Establishments and Control Laboratories... (6), and the twenty-second report of the Expert Committee on Biological Standardization, Annex 3: “Development of a national control laboratory for biological substances...” (7).)