1.1. BACKGROUND
Radionuclides, and the radiopharmaceuticals derived from them, are an established tool for key investigations in numerous disciplines of the life sciences and for diagnosis and treatment of many life threatening diseases. A large number of Member States are in the process of setting up new cyclotron facilities for the production of radiopharmaceuticals for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Some of these cyclotrons are also planned to be multidisciplinary facilities not only for isotope and radiopharmaceutical production, but also for other purposes such as materials research and analytical techniques using charged particles. The types of facilities needed depend on the type of radionuclides to be produced, their quantity, as well as the type of their application. This report is intended to help those Member States in the process of setting up a cyclotron facility for the production of radionuclides and radiopharmaceuticals, as well as for other applications.
1.2. OBJECTIVE
The decision to install a new radioisotope production facility is generally based on national and institutional policies on science, technology and healthcare. Establishing a cyclotron facility for producing radionuclides and/or manufacturing radiopharmaceuticals is a complex process and requires careful planning in order to be successful. In addition to the technological complexity requiring a highly skilled staff, it is also costly to build and to operate. The aspiration to build such a facility is the first step. The next step is the commitment of the government or funding agency to the project and the development of the scope of the facility in relation to the national interests for healthcare or research.
This publication provides guidance once the political/economic decisions to build a facility have been made, although it may be useful in the decision making process as well. What must follow these higher level decisions is a critical evaluation of the project and the recognition that many interrelated factors must be considered during planning and implementation. Lack of attention to these factors can lead to poor decisions with costly ramifications.
Conversely, a judicious assessment should result in the successful fulfilment of the goals of the project.
Thus, the primary objective of this book is to help Member States in making the decision on which type of cyclotron installation is most appropriate for them and to highlight the critical design issues, which must be considered for establishing a successful centre.
1.3. SCOPE
This publication provides technical guidelines for planning new radionuclide manufacturing facilities; however, it does not address governmental policies or financial implications. It covers the most important design and technical aspects, including, but not limited to, feasibility study and strategic planning, facility requirements and design, staffing, radiation protection, good manufacturing practices (GMP), and quality management.
Each topic is discussed in terms of the experience of experts in designing, installing and managing a variety of radioisotope facilities around the world.
The design issues related to large scale multipurpose accelerator installations are beyond the scope of this book.
1.4. STRUCTURE
This publication is divided into ten sections and nine appendices.
Section 2 provides a categorization of cyclotron centres suitable for radionuclide and radiopharmaceutical production and addresses project planning and defining the appropriate scope of the new facility. This includes the formation of a task force for planning, potential applications, a cost–benefit analysis, and a business plan.
Section 3 discusses various aspects of cyclotron facility design and construction, particularly addressing the installation of cyclotrons and related utilities. Section 4 is devoted to the design of laboratory spaces, workflow patterns and environmental conditions necessary to achieve the pharmaceutical quality in products. Section 5 catalogues the equipment necessary to carry out routine operations. This chapter also discusses personnel requirements for efficient operation. Qualified staff with appropriate training is essential for manufacturing radiopharmaceuticals that conform consistently to the required specifications. Section 6 gives some examples of cyclotron facilities whose primary goal is radionuclide and radiopharmaceutical production and discusses the design principles of those facilities.
Radiopharmaceuticals, being pharmaceutical products, must be regulated in terms of production and use. Section 7, on quality management systems and
Section 8, on good manufacturing practices (GMP), discuss in detail the essential elements related to the requirements of radiopharmaceutical manufacture including various types of controls, process monitoring and documentation for manufacturing radiopharmaceuticals of acceptable quality.
Adherence to the requirements specified in these chapters forms the backbone of a manufacturing system that must be planned and implemented in compliance with the local regulatory bodies where appropriate. In the absence of specific regulations in a Member State, the discussion provided in this book may be employed as guidelines in conjunction with other regulations such as those from the World Health Organization, the European Union and the United States Food and Drug Administration.
Section 9, on radiation protection, describes arrangements for the safety of personnel and the general public following the safety guidance of the IAEA in radionuclide production facilities. Section 10 gives a brief summary of this publication.
Finally, Appendix 1 provides an extensive list of key issues related to facility consideration, Appendix 2 gives some examples of radiological work permits and associated forms, Appendix 3 tabulates an extensive checklist for establishing a sound quality management system, while Appendices 4–9 provide several examples of standard operating procedures and batch records related to radiopharmaceutical production.