Formulation of radiopharmaceuticals

Formulation of radiopharmaceuticals

Preparation of radiopharmaceuticals for clinical administration necessi-tates several considerations. For example:

1. Sterility: All formulations intended for parenteral administration need to be manufactured under aseptic conditions that provide a rea-sonable assurance of sterility. In addition, absence of microbial con-tamination needs to be shown periodically to validate such a working environment. Aseptic filtration as the final step in the process and/or terminal sterilization after packaging in the final container, for exam-ple, by autoclaving, are the preferred practices that ensure sterility of the formulation in the final product container.

2. Pyrogens and endotoxin limit: Endotoxins are bacterial cell-wall components that can elicit fever response in humans and are there-fore called pyrogenic. Endotoxin content of the formulations must be within the limits that would ensure that the rate and total daily amount of endotoxin intake in the patients stay below acceptable regulatory limits. The endotoxin limit for human administration is limited to five endotoxin units (as defined by the United States Pharmacopeia [USP]) per kilogram per hour (in the case of infusion) for intravenous (IV) administration. All incoming raw materials, including glassware contact surfaces and packaging materials, and processing techniques can contribute to the endotoxin content of the final formulation.

3. Adsorption of the radiopharmaceutical to the container of storage or dispensing can lead to reduced dose or potency administered to the patient. This can be obviated by using silicone-coated low-adsorption containers as—well as by using inert carrier-loaded radiopharmaceu-ticals, which have lower diffusivity and adsorption potential.

Certain radioisotopes have short half-life, which introduces additional complexity in their use. For example, ^99mTc and ^113mIn have a short half-life. The parenteral formulations of these radioisotopes must be prepared in the clinic under aseptic conditions, ideally immediately before administration to the patient.

Institutions, such as hospitals, that handle radioisotopes have a medical isotope committee to carefully guide, monitor, and control the handling of the radioisotopes to maintain patient and user safety. Generally, the institutional medical isotope committee is charged with the responsibil-ity to define the specific details of radioisotope use and disposal, such as facilities, storage requirements, inventory requirements, and personnel procedures.