and glossary1,2
Introductory note
The first World Health Organization (WHO) draft text on good manufacturing practices (GMP) was prepared at the request of the Twentieth World
Health Assembly (resolution WHA20.34) in 1967 by a group of consultants. It was subsequently submitted to the Twenty-first World Health Assembly
under the title “Draft requirements for good manufacturing practice in the manufacture and quality control of drugs and pharmaceutical specialities” and was accepted.
The revised text was discussed by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in 1968 and published as an annex to its twenty-second report (1). The text was further reproduced (with some revisions) in 1971 in the Supplement to the second edition of The international pharmacopoeia.
When the World Health Assembly recommended the first version of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce in resolution WHA22.50 (1969), it accepted at the same time the GMP text as an integral part of the Scheme. The revised versions of both the Certification Scheme and the GMP text were adopted in resolution WHA28.65 in 1975. Since then, the Certification Scheme has been extended to include certification of:
— veterinary products administered to food-producing animals;
— starting materials for use in dosage forms, when they are subject to control by legislation in the exporting Member State and in the importing Member State; and
— information on safety and efficacy (resolution WHA41.18, 1988).
The GMP text, however, has not been revised since 1975.
Considerable developments have occurred in GMP in the intervening years, and important national and international documents including new revisions have appeared, such as:
— Guide to good pharmaceutical manufacturing practice 1983. London, Her Majesty’s Stationery Office, 1983 (“Orange Guide”). [Superseded by the 1992 EEC guide.]
— Bonnes pratiques de fabrication et de production pharmaceutiques. Paris, Ministère des Affaires Sociales et de la Solidarité Nationale, Secrétariat d’Etat chargé de la Santé, Direction de la Pharmacie et du Médicament, 1985. [Superseded by the 1992 EEC guide.]
— ASEAN good manufacturing practices guidelines, 2nd ed. Association of South East Asian Nations, 1988.
— Good manufacturing practice for medicinal products in the European Community. Commission of the European Communities, 1992.
— Guide to good manufacturing practice for pharmaceutical products. Convention for the Mutual Recognition of Inspection in Respect of the Manufacture of Pharmaceutical Products (PIC), 1992.
New types of guidelines have appeared in recent years: GMP texts applicable
to the manufacture of bulk pharmaceutical chemicals as opposed to the manu-facture of formulations of dosage forms (PIC guidelines, 1987; various national documents). Another important development in the industry at large is the appearance of the guidelines of the International Organization for Standar-dization (ISO), specifically the ISO 9000 to 9004 standards for quality systems (1987 rev. 1990). These developments, together with plans to expand and revise the Certification Scheme call for the revision of the WHO GMP text.
The revised draft requirements for GMP are presented in three parts. Part One, “Quality management in the drug industry: philosophy and essential elements”, outlines the general concepts of quality assurance as well as the principal components or subsystems of GMP, which are joint responsibilities of the top management and of production and quality control management. These include hygiene, validation, self-inspection, personnel, premises, equipment, materials, and documentation.
Part Two, “Good practices in production and quality control”, provides guidance on actions to be taken separately by production and by quality
control personnel for the implementation of the general principles of quality assurance.
Part Three contains two supplementary guidelines, but it is an open-
ended section, and it is anticipated that further guidelines will be developed
in the future, e.g., for biological products, materials for clinical trials, and validation.
The provisions in this guide are fully consonant with those in the above-mentioned documents published by the EEC and PIC.
General considerations
Licensed pharmaceutical products should be manufactured only by licensed manufacturers (holders of a manufacturing authorization) whose activities are regularly inspected by competent national authorities. This guide to GMP shall be used as a standard to justify GMP status, which constitutes one of the elements of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce, through the assessment of applications for manufacturing authorizations and as a basis for the inspection of manufacturing facilities. It may also be used as training material for government drug inspectors, as well as for production and quality control personnel in the industry.
The guide is applicable to all large-scale operations for the production of drugs in their finished dosage forms, including large-scale processes in hospitals and the preparation of clinical trials supplies.
The good practices outlined below are to be considered general guides,1 and they may be adapted to meet individual needs. The equivalence of alternative approaches to quality assurance should be validated. Parts One and Two of this guide are not intended to cover the production of active pharmaceutical ingre-dients for which specific requirements are presented in section 18. Nor does the guide as a whole cover safety aspects for the personnel engaged in manufacture: those are governed by national legislation. However, the manufacturer must assure the safety of workers. Nonproprietary names for pharmaceutical sub-stances designated by WHO should be used when available, together with other designated names.
In the drug industry at large, quality management is defined1 as the aspect of management function that determines and implements the “quality policy”, i.e., the overall intentions and direction of an organization regarding quality, as formally expressed and authorized by top management.
The basic elements of quality management are:
— an appropriate infrastructure or “quality system”, encompassing the organizational structure, procedures, processes, and resources; and
— systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for quality. The totality of these actions is termed “quality assurance”.
Within an organization, quality assurance serves as a management tool. In contractual situations, quality assurance also serves to generate confidence in the supplier.
In drug manufacture and supply the terminology may differ. In particular,
the term “quality system” is rarely used, and it is “quality assurance” that
usually embraces such elements as organizational structure, procedures, and processes.
The concepts of quality assurance, GMP, and quality control are interrelated aspects of quality management. They are described here in order to emphasize their relationship and their fundamental importance to the production and control of pharmaceutical products.
No comments:
Post a Comment