(2003; 148 pages)
5.1 Standard operating procedures (SOPs) must be available for all operating procedures and should be regularly reviewed and kept up to date for all manufacturing operations. All entries on batch records should be initiated by the operator and independently checked by another operator or supervisor.
5.2 Specifications for starting materials should include details of their source, origin and (where applicable) method of manufacture and of the controls used to ensure their suitability for use. Release of a finished product should be conditional on satisfactory results being obtained in the tests on starting materials.
5.3 Careful consideration should be given to the validation of sterilization methods.
5.4 A wide variety of equipment is used in the preparation of radiopharmaceuticals. Equipment for chromatography should, in general, be dedicated to the preparation and purification of one or several products labelled with the same radionuclide to avoid radioactive cross-contamination. The life span of columns should be defined. Great care should be taken in cleaning, sterilizing and operating freeze-drying equipment used for the preparation of kits.
5.5 A list of critical equipment should be drawn up, including any equipment such as a balance, pyrogen oven, dose calibrator, sterilizing filter, etc., where an error in the reading or function could potentially cause harm to the patient being given the final product. These devices should be calibrated or tested at regular intervals and should be checked daily or before production is started. The results of these tests should be included in the daily production records.
5.6 Specific equipment for radioactive measurements may be required as well as radioactive reference standards. For the measurement of very short half-lives, national central laboratories should be contacted to calibrate the apparatus. Where this is not possible, alternative approaches, such as documented procedures, may be used.
5.7 In the case of labelling kits, freeze drying should be carried out as an aseptic procedure. If an inert gas such as nitrogen is used to fill vials, it must be filtered to remove possible microbial contamination.
5.8 The dispensing, packaging and transportation of radiopharmaceuticals should comply with the relevant national regulations and international guidelines (5).