**1. Introduction**

During the '80s radiopharmaceuticals were considered as tracers used in hospital centres under the responsibility of a person with a sound knowledge in the safe use of radiation. It was in 1989 when radiopharmaceuticals were considered for the first time in the European Union as medicinal products after entry into force the Council Directive 89/343/EEC [1]. In this Directive was stated the first official radiopharmaceutical definition as:

*"any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose."*

Radiopharmaceuticals are used in major clinical areas for diagnosis and therapy. They usually have no pharmacologic effects, as they are used in tracer quantities. Consequently, there is no dose–response relationship, which thus differs

significantly from conventional medicinal products. Radiation is an inherent characteristic of all radiopharmaceuticals, and patients always receive an unavoidable radiation dose. In the case of therapeutic radiopharmaceuticals, radiation is what produces the therapeutic effect.

The manufacturing and handling of radiopharmaceuticals is potentially hazardous. The level of risk depends in particular upon the types of radiation, the energy of radiation and the half-lives of the radioactive isotopes. The facilities and procedures for the production, use, and storage are subject to licencing by national and/or regional authorities. This licencing includes compliance both with regulations governing pharmaceutical preparations and with those governing radioactive materials.

Considering the special nature of radiopharmaceuticals, strict adherence to conventional good manufacturing practices is not possible in many scenarios where radiopharmaceuticals are handled. It is necessary to balance aseptic handling practices (patient safety) with radiation protection practices (worker safety) complying with the current *As Low As Reasonably Achievable* (ALARA) requirements. Moreover, a demanding technical difference and challenge is that in most cases, diagnostic radiopharmaceuticals need to be prepared, controlled and used within a short time of a few hours or even minutes due to the physical half life of the radionuclides.

Specific guidance is available on adaptations to the conventional regulatory framework to address challenges of the preparation of radiopharmaceuticals.
