The quality of a drug or device is one of the criteria for market approval and is reviewed as part of the registration process. Quality assurance covers all activities aimed at ensuring that consumers and patients receive a product that meets established specifications and standards of quality, safety and efficacy. It concerns both the quality of the products themselves and all the activities and services that may affect quality.
Responsibilities of the various actors
Ensuring drug quality is the responsibility of all those involved - from the production of drugs to distribution and dispensing. Both the public sector and the private sector have their share of responsibilities. Detailed discussion of the various groups’ responsibilities is found in the relevant sections - specifically those on storage and distribution in the drug supply management area. The following may serve as an overview of responsibilities:
Manufacturers are responsible for developing and manufacturing a good quality product and should adhere to GMP. They should also document their procedures and activities, to ensure the quality of the product.
The drug regulatory authority must ensure that drugs approved for marketing are appropriately evaluated and registered; that manufacturers comply with GMP through licensing and inspection; that the quality of imported drugs is ensured, for example through the WHO Certification Scheme; and that drug quality is maintained in the supply system by ensuring good storage and distribution practices, and monitoring the quality of drugs in the distribution chain.
Those involved in drug procurement should ensure that drugs are carefully selected, purchased from reliable sources, inspected at the time of receipt, and stored and transported properly. The necessary laboratory testing must be requested, and mechanisms to report quality defects and a recall procedure must be in place.
Those involved in distribution and dispensing must ensure the proper storage of products, and their appropriate handling, packaging and dispensing. They must also inform patients about the correct handling and storage of drugs.
A mandatory system of licensing manufacturers, importing agents and distributors is essential to ensure that all products conform to acceptable standards of quality, safety and efficacy. In addition, all premises and practices used to manufacture, store and distribute these products must comply with requirements to ensure continued conformity to standards until products are delivered to the end-user.
Before a formal licensing system can become operative, it is necessary to: adopt a precise definition of the various categories of licence-holders; determine the content and format of licences; detail the criteria on which licence applications will be assessed; and provide guidance to interested parties on the content and format of licence applications, and on the circumstances in which an application for renewal, extension or variation of a licence will be required.
Inspection is an important strategy for safeguarding drug quality. It is intended to ensure that all activities in drug manufacture, import, export, distribution, etc. comply with regulatory and quality assurance requirements, as well as with regulations. Inspection requires motivated, well-trained and properly remunerated staff. WHO guidelines on inspection are available, and contain check-lists for inspectors, sample forms, standard formats for reports and many useful references.48, 49
Good manufacturing practices
Overall quality assurance of drug manufacture, including the proper organization of production and control activities, is essential to ensure good quality. These practices are defined in GMP guidelines.50 Following GMP standards not only guarantees production quality, but may also save money by reducing the number of substandard batches that must be remanufactured or destroyed.
Information about GMP can be communicated between national regulatory bodies through the use of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (see Box 8).47
The WHO Certification Scheme on the Quality of
Pharmaceutical Products Moving in International Commerce
The WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in Internacional Commerce47, 51 aims to increase and standardize the exchange of information between regulatory agencies. This is especially relevant for drug importing countries with limited resources for regulatory control. Under the provisions of the Scheme the DRA of the exporting country must provide a certificate that gives the following information:
• A statement that the drug is registered and permitted to be sold in the exporting country, and the date and number of the registration. If the drug is not registered, the reasons must be stated.
• A statement that the product information attached to the certificate is that approved for use in the exporting country.
• Confirmation that the manufacturer’s facilities are inspected regularly and that they comply with WHO standards of GMP and quality control.
The Scheme is non-mandatory and depends on the good faith of the competent authorities in exporting countries. A certificate can never be more reliable than the agency that has issued it. A country may join the scheme exclusively as an “importing” (certificate-receiving) country, even if it also exports drugs. The Scheme provides the importing authority with information on the status of a product from the exporting country’s DRA. It is intended, however, to strengthen licensing and registration in importing countries, not to replace them. It does not cover the transit and storage conditions that exist once products have been released by the manufacturer. Free sale certificates should not be used, as they do not cover data on government inspections and approved indications.
Drug quality control laboratories are responsible for checking, by appropriate testing, whether drugs are of the required quality. The resources and technical capacity to carry out these activities at country level vary enormously, but each DRA should have access to a quality control laboratory, which will also play an important role in the registration process and in the surveillance of the quality of marketed products.
A drug quality control laboratory is costly to establish and to maintain. In general it is recommended that all countries should at least have access to a small laboratory where basic tests can be performed, and that such basic facilities are gradually expanded. It may be that the tests can be done properly and more cost-effectively in an existing institution, such as a university pharmacy department or an independent laboratory. Furthermore, there are international quality control laboratories that can provide drug analyses at fairly reasonable prices. WHO has developed practical guidelines for establishing small and medium-sized testing facilities.52, 53
As drug quality control laboratories require considerable human and financial resources, they can be established and run by a managerially independent drug regulatory agency. The running costs of both bodies can then be funded from the income from registration fees. This often works well, as registration fees may generate considerable income, while laboratory services usually do not. In manufacturing countries, establishing quality control departments within drug manufacturers and wholesalers/distributors may be a prerequisite for the issue of licences. There should be a high level of control, under the strict supervision of government inspectors and the national drug quality control laboratory.