Report of the consultants meeting on good manufacturing practices and clean room requirements for radiopharmaceuticals

Radiopharmaceuticals are compounds containing radioisotopes that are used in nuclear medicine for a variety of diagnostic studies and, to a limited extent, for therapy. Almost 80% of the diagnostic studies are carried out with 99mTc containing radiopharmaceuticals (half-life, six hours). Recently, another class of radiopharmaceuticals contains the ultra short-lived isotopes 11C, 13N and 15O as well as 18F, which are mostly produced and immediately used in the hospital cyclotron Positron Emission Tomography (PET) facilities. In therapy, 131I is widely used for thyroid disorders, 32P for treatment of abnormal increase in circulating red blood cells, while 153Sm and 89Sr are used for palliation of pain in patients suffering from bone metastases. They contain very small amounts of chemical ingredients, normally do not have any pharmacological effects, and are administered in small volumes. Radiopharmaceuticals are produced, used and exported both in developing and developed countries. The scale of production is small compared to conventional pharmaceuticals. Monographs on radiopharmaceuticals can be found in many pharmacopoeias, such as BP, USP, EP and other compendia. This field is also marked by active research and development of new products both for diagnosis and therapy. Traditionally, production and supply of radiopharmaceuticals started as research activities of national nuclear laboratories operating reactors and cyclotrons. Certain products found useful and effective were continued to be provided to the clinics as a service from the nuclear centres. In developed countries demand of radiopharmaceuticals is so considerable that production and sale are increasingly taken over by commercial companies. On the other hand, in many developing countries, demand is still limited, and radiopharmaceutical production and supply still remain more of a service operation at the national nuclear centres. Depending on the radioactivity levels handled, production has to be carried out in special facilities often with shielding and remote handling to protect the operators from radiation exposure. There are international norms for radiation exposure allowed for radiation workers and strong national organizations for monitoring and implementing radiation protection measures. Being part of the national nuclear programmes, radiopharmaceutical production has been from the very beginning subjected to regulations of radioactive material handling, transportation and use. However, the systems of surveillance and control for pharmaceutical products have not been implemented in many places to the same extent as for radiation protection. There are also technical difficulties in harmonizing the requirements of radiation safety and pharmaceutical safety. Simultaneously, there have been several technical developments in the field of Quality Assurance of pharmaceuticals. The concepts of Good Manufacturing Practices (GMP) and the requirements for clean rooms define quality of air for pharmaceutical production areas. Efforts have been made in recent years to apply these concepts also to radiopharmaceutical production. Significant progress appears to have been made in the developed countries and in the technology needed to fulfil these standards. The technical problems in upgrading the facilities of radioisotope laboratories to conform with the clean air requirements and the cost involved are still to be clearly understood in many developing countries. In many countries the regulatory authorities apply the same set of regulations for radiopharmaceuticals as for other pharmaceuticals. Some guidelines for radiopharmaceuticals have been published, e.g. Scandinavian, US FDA, Australian, Canadian and EU guidelines. No such guidelines are yet available from international agencies such as the International Atomic Energy Agency (IAEA) or World Health Organization (WHO). A guideline from an international body of this nature would be very useful for institutions working with radiopharmaceutical products as well as regulatory authorities, particularly in developing countries. A Consultants Meeting was organized to discuss the technical issues involved in the application of GMP and clean room concepts to radiopharmaceutical products and explore means of adapting them in a cost effective way