As outlined in WHO’s Guiding Principles for Small National Drug Regulatory Authorities (1) an important task for a drug regulatory authority (DRA) is to institute a system which subjects all pharmaceutical products to premarketing evaluation, marketing authorization and postmarketing review to ensure that they conform to required standards of quality, safety and efficacy. Because it has responsibilities in public health, in most countries the DRA is located in, linked to or reports to the Ministry of Health. This manual is intended to provide guidance to countries which do not already have a fully functioning system of premarket evaluation and market authorization, and have a particular interest in the assessment and authorization of multisource (generic) pharmaceutical products. Many of the principles apply to other groups of medicines (such as complex biologicals and ‘alternative’ preparations), but the details may be specific to multisource products.

For the purposes of this manual, the term drug regulatory authority means a network that administers the full spectrum of drug regulatory activities, including at least the following functions and others:

X Marketing authorization for new products and variation of existing authorizations;

X Quality control laboratory testing;

X Adverse drug reaction monitoring;

X Provision of drug information and promotion of rational drug use;

X Good Manufacturing Practice (GMP) inspections and licensing of manufacturers, wholesalers and other distribution channels;

X Enforcement operations;

X Monitoring of Drug Utilization.

In some regulatory systems the functions of an individual DRA may be more limited. The manual may still be used when, for example, the DRA is confined to marketing authorization activities.

This manual provides detailed guidance on the structure and operation ofthose functions of a DRA that deal with premarket evaluation and marketing authorization, also known as drug registration. The other activities are a necessary complement to the marketing authorization function but are not discussed in detail in this document. The principles underpinning premarket evaluation and the marketing authorization process are discussed in WHO’s Guiding Principles for Small National DRAs (1).

The advice in this manual is intended to be independent of local political and legal structures. Instead of being prescriptive, it describes options from which governments can select the most suitable path, depending on current circumstances.

Marketing authorization applications can be classified broadly in three groups, which comprise applications for:

1. Products containing new chemical or biological active pharmaceutical ingredients (APIs);

2. Multisource pharmaceutical products (generic products): that is, new marketing authorization holders, formulations, or sources of well established drugs;

3. Variations to existing marketing authorizations.

Evaluation of the complex toxicological and clinical data which accompany new chemical entities requires resources and experience that are usually found only in national DRAs with substantial funding and skills. Countries with more limited resources may wish to give priority to well established drugs. They can then await the outcome of detailed premarketing evaluation of safety and efficacy, and postmarketing surveillance of safety, by the well resourced authorities before considering issuing marketing authorizations for newer drugs (see Part III “Collaboration with other DRAs”). If a new drug appears to be important for an endemic disease, a report may be available on request from one of the well resourced DRAs. If not, WHO is usually able to provide technical advice.

A number of existing WHO guidelines that are directly relevant to this manual are reproduced in full as Annexes. Updates of these guidelines are issued from time to time, and it is the current issue that will usually be the most relevant. Key terms used in the manual are defined in the Glossary.