The guidelines in this manual are confined to multisource pharmaceutical products containing well established drugs which do not require submission of the complex toxicological and clinical data that accompany new chemical entities. Many of the principles apply to other groups of pharmaceuticals (such as complex biologicals, “alternative” preparations and veterinary medicines) but the details may not. Separate guidelines already exist for herbal medicines (9). In many countries regulation of veterinary preparations is undertaken by a different agency.

Details in this manual apply to antibiotics and substances which, although of biological origin, are of low molecular weight and can be isolated as pure substances, such as purified steroids and alkaloids.

On the other hand, the details do not apply to more complex biological substances of higher molecular weight whose purity, potency and composition cannot readily and reliably be determined by chemical or physicochemical analysis. Examples of this group include vaccines, blood products, modified animal tissues, high-molecular-weight hormones, allergens, and the products of genetic engineering or other newer biotechnological techniques.

New licence holders can rarely, if ever, be approved for the second group of biological products only on the basis of in vitro comparison with the comparator product. Different brands may have the same use, for example pertussis vaccine, but each must independently have been shown to be safe and effective. They may even have different dose regimens. Data on plasma concentrations of the “active ingredient” are also usually unhelpful because it is unclear whether precisely the same entity is being measured. These products cannot therefore be approved without safety and efficacy data, and are not the subject of this guideline. The model application form (Annex 6) is not suitable for this group.

WHO is currently developing guidelines on the assessment and marketing authorization of vaccines.

The present guidelines apply to both prescription and non-prescription (“over-the-counter” or OTC) drug products. Products that are authorized for OTC dispensing are assumed to entail lower risk for users than prescription products. Thus, if resources are limited, DRAs may choose to give priority to prescription drug products when committing resources to assess the quality aspects of applications. Control of product information and promotional material, on the other hand, can be equally important for OTC products in order to encourage appropriate use and keep the use of the patient’s personal resources for ineffective or less effective therapy to a minimum.

This manual is not intended to address the question of counterfeit drugs, which is being taken up separately by WHO (10). A further manual containing observations and recommendations to combat counterfeit drugs is in preparation (11).