Performing a sterility test on radiopharmaceuticals involves significantly greater complexity than testing conventional pharmaceuticals. In this context, operator protection plays a crucial role: in addition to the risks associated with decontamination processes, the presence of radioactive substances must also be managed safely.
For this reason, every component of the isolation system must be carefully studied and designed in detail, adopting specific engineering and operational solutions. Below, we provide an overview of some of the key aspects to consider in order to achieve reliable and safe results.
Safety During Operation
Working Under Negative Pressure
A fundamental safety strategy is to operate under negative pressure. This configuration ensures operator protection even in the event of micro-leaks from the isolator, reducing the risk of particle release into the surrounding environment.
Composite Shielding Based on the Type of Emitted Radiation
One of the most critical aspects is shielding, which must be designed according to the type of radiation emitted. Alpha particles, for example, require relatively simple shielding solutions, whereas beta radiation presents greater challenges due to the potential generation of bremsstrahlung radiation.
To minimize this phenomenon, PMMA (polymethyl methacrylate) panels are installed inside the isolator. As a low atomic number material, PMMA effectively absorbs beta particles while reducing the generation of secondary radiation. An external lead layer is then added to the PMMA and steel combination, providing protection against gamma radiation—the most penetrating type—and eliminating the residual risk associated with bremsstrahlung radiation.
Shielding Thickness Sizing Based on the Radiation Source
The selection of shielding material thicknesses should never be standardized but should result from a thorough analysis of both the radiation penetration capability and the amount of radiation emitted. Proper sizing ensures maximum protection without unnecessarily increasing the weight of the isolator, thus avoiding issues related to the floor load capacity of the installation area.
Additional Chest Protection
Sterility testing requires certain manual operations, performed through plastic gloves mounted on a tempered glass front panel. When handling alpha- and beta-emitting substances, the shielding provided by these materials is sufficient to ensure operator safety throughout the testing process.
However, particular attention must be given to chest protection, as it houses vital organs. For this reason, an additional movable glass panel is installed externally to the front viewing window, designed to balance visibility and safety. This shield, consisting of a PMMA layer and a lead glass layer, provides protection measurable in centimeters of lead equivalent and can be translated to allow access to the working chamber.
Safety During Maintenance Activities
Bi-Bo Filtration System
Safety considerations extend beyond routine operations and also apply to maintenance activities. The Bi-Bo (Bag-In/Bag-Out) filtration system allows contaminated HEPA filters to be replaced without exposing operators to trapped materials, significantly reducing the risk of inhaling alpha particles, which can be hazardous even in extremely small quantities.
Liquid Waste Management
Another critical aspect is the management of liquid waste generated during sterility testing. The radiopharmaceutical and the solutions used during the process are collected in a storage tank, which itself becomes a source of ionizing radiation. The use of shielded mobile carts allows these liquid effluents to be handled safely, applying the same protection principles adopted for the isolator.
Level Monitoring and Spill Prevention
To prevent potentially hazardous situations, storage containers are equipped with level sensors integrated into the isolator’s automation system. This enables operators to continuously monitor the remaining capacity and, if necessary, automatically stop the peristaltic pump, thereby preventing any risk of overflow or leakage.
Towards Greater Automation
Future developments are aimed at increasing the level of automation, with the goal of further reducing direct operator involvement. The use of anthropomorphic robots could enable the management of certain sterility testing activities, limiting human exposure to loading and waste disposal operations only.