Radiopharmaceuticals radiation protection

Production, transportation, and use of radiopharmaceuticals, as radioactive products, is governed by regulatory agencies dealing with radiation protection and nuclear safety. 

Operator Radiation Protection Even for the largest commercial manufacturer of radiopharmaceuticals, the batch volumes are small compared to nonradioactive pharmaceuticals. So even a scaled-up production batch can be contained within a limited space. When scaling up a radiopharmaceutical production, one always has to assure that the radiation outside the contained work unit is acceptable for the operator. 

The design of a radiopharmaceutical production process depends very much upon the kind of radiopharmaceutical to be made. Although most radiopharmaceuticals are intended for parenteral use, also oral radiopharmaceuticals in different forms are widely used. One must emphasize different factors when planning for production of parenteral radiopharmaceuticals compared to oral radiopharmaceuticals. Still, a common factor is the involvement of radioactive materials, and the radiation protection of the personnel must always be an integral part of the design. 

Preparation equipment should be designed so it can be easily and thoroughly cleaned. Procedures for cleaning, sanitation, and storage of production equipment used in radiopharmaceutical production must be established. Special training is necessary for personnel involved in this kind of work with regard to both clean-room aspects and radiation protection aspects. 

The position of the radionuclide in the molecule of interest is also critical as it will affect the biological behavior of the radiopharmaceutical. Chemical reactions must be designed to be stereospecific in many cases, as the production of a mixture of different stereoisomers complicates the purification of the final radiopharmaceutical. Synthesis procedures must also be easy to automate, as very elevated activities are used for the synthesis of PET radiopharmaceuticals (several curies usually) and appropriate radiation protection systems must be used. 

For personnel working with radiopharmaceuticals, training and qualification should cover general principles of GMP and radiation protection. This includes also personnel in charge of cleaning premises and equipment used for this type of production. All manufacturing operations should be carried out under the responsibility of a QP with additional competence in radiation protection. 

Visual Inspection of Finished Product As part of the quality control, all parenter-als will be subject to an inspection for the possible content of particles. Visual inspection of radiopharmaceuticals is more complicated than for other pharmaceuticals, as radiation protection guidelines strongly discourage any direct eye contact with radioactive sources. Normally, the visual inspection of a radiopharmaceutical is performed by placing the vial on a rotating station connected to a camera. The station is properly shielded, and the operators can study the solution on a distant screen. 

The Medicines Commission also includes four civil servants (pharmacists) with an advisory capacity the inspector general of pharmacies the director of the Institute of Hygiene and Epidemiology a pharmacist designated by the minister responsible for social security and the inspector general of the Radiation Protection Division (for radiopharmaceuticals and medicincil products treated with ionizing radiation). These civil servants can also be represented by their deputies. 

Identity and purity, stability, and sterility and apyrogenicity. The identity and purity of radiopharmaceuticals is verified by determining the radionuclidic and radiochemical purity. Stability concerns the radioactive label, which is related to radiochemical purity at a certain time after preparation. Since Tc pharmaceuticals are formulated as sterile, pyrogen-free solutions, the safety requirements of drugs for parenteral use do apply. Safe handling of the radionuclide is equally important and must comply with Euratom Directives, regulated by national law for radiation protection, which also concerns the application of radionuclides in adults and in children for diagnostic procedures. 

This chapter deals with neither the efficacy of radiopharmaceuticals nor the radiation protection of patients and workers in connection with the handling of radiopharmaceuticals. 

International Commission on Radiation Protection (1987) Annals of the ICRP, radiation dose to patients from radiopharmaceuticals, biokinetic models and data. ICRP publication 53, vol. 18, no. 1-4. Pergamon, Oxford... 

Type 2 isolators for use with radiopharmaceuticals should incorporate an appropriate radiation protective system against ionising radiations. 

As with all pharmaceutical preparations, radiopharmaceuticals should undergo a visual examination. The examination should take into account radiation protection issues for the operator and be conducted as quickly as possible with the preparation behind suitable shielding. Vials should be examined for insecure closures, cracks, glass particles in the liquid, and particulate contamination. Syringes should also be examined for particulate contamination. 

For routine labeling of radiopharmaceuticals, the most convenient procedures are recommended because time is a factor barely available for chemists, especially from the physician s point of view. Needless to state, the physical half-life of the more exotic iodine radioisotopes requires similar efforts. Thus, simple pipetting steps are mandatory for the preparation to fulfill the requirements speed and radiation protection. In addition, pipetting steps can be automated and help to optimize the latter aspect. 

The terms medical exposure and medical radiation protection refer to patients. In addition, members of the family and close friends either in the hospital or at home, who may come close to the patients following administration of radiopharmaceuticals, plus volunteers in biomedical research studies, belong to this category of exposure. The exposure of doctors and... 

Legislation for extemporaneous preparation of radiopharmaceuticals is in principle not different from extemporaneous preparation in general (Sect. 35.5). There is a great variation in interpretation and approach in Europe [14]. In some countries radiopharmaceuticals are prepared based on the pharmacy status of the radiopharmacy unit. In other countries radiopharmaceuticals are prepared in laboratories, in university institutions or research laboratories without pharmacy status, with authorisation based on radiation protection legislation only. 

A radiopharmacy has dedicated equipment for synthesis, preparation and quality control of radiopharmaceuticals. The workbench for the safe and aseptic preparation of radiopharmaceuticals is often a sufficiently lead shielded radiopharmacy safety cabinet with downflow HEPA filtered laminar air providing a GMP class A working zone. The exhaust air is filtrated and expelled outside the radiopharmacy to the roof on top of the building. The cabinet has built-in radiation protection by installed lead plates in the walls and in the working field, a horizontally movable lead containing glass window, lead shielded instruments for radiation measurement and waste containment and special equipment for automatic preparation and dispensing such as a barcode seamier, printer, screen and mouse pad. 

Like other preparations, radiopharmaceuticals must be labelled with the required information. In most situations, the label has to be attached to the shielding needed for radiation protection. 

Radiation dose to patients from radiopharmaceuticals. A Report of a Task Group of Committees 2 and 3 of the International Commission on Radiological Protection (ICRP). Oxford, UK Pergamon Press, 1994. 

International Commission on Radiological Protection (1987) Technetium-labelled albumin (HSA). In Annals of the ICRR Radiation dose to patients from radiopharmaceuticals, biokinetic models and data. ICRP publication 53, vol 18, no 1-4. Pergamon, Oxford, p 173 Lamson III M, Callahan RJ, Castronovo FP, McKusick KA, Potsaid MS (1974) A rapid index of free activity in preparations of Tc-albumin. J Nucl Med 15 1061-1062 Lin SM, Winchell HS, Shipley BA (1971) Use of Fe(II) or Sn(II) alone for technetium labelling of albumin. J Nucl Med 12 204-211... 

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