GMP compliant small-scale Production Facility for Tc-99m-sterile Generators

(Aseptic loading procedure for up to 50 generators per batch with max. 2500 GBq of Mo-99)

General layout

The production facility for -sterile 99Mo/99mTc-generators consists of a shielded loading hot cell and a dispensing hot cell. The loading hot cell is connected with a preparation unit (laminar flow module or glove boxes) outside. The preparation unit is used for the transfer of the inactively assembled generators via a roller conveyor into the loading hot cell, and for the final assembly of the already loaded generators. The dispensing hot cell is used for the processing of the 99Mo-loading solution for the loading of the generators. The inner dimension of the lead-shielded hot cells is 1000 mm x 1000 mm x 1000 mm (H x W x D). The access doors of the hot cells can be installed at the operator or at the rear side. (depending on the layout of the generator facility)

The shielding of the hot cells is made of 100 mm thick lead for the vertical walls, 70 mm thick lead for the bottom and ceiling walls. The shielding meets the international requirements to keep the radiation exposure to the workers under 5 µSv/h at any time (max. 2500 GBq of 99Mo). The dispensing and the loading hot cell are separated by a wall with a lead shielding of 50 mm. There are access doors in order to open the hot cells in case of maintenance. The windows of the hot cells are made of 230 mm thick lead glass with a density of 5.2 g/cm3. Below the hot cells bottom there is sufficient space for waste collecting containers and the docking of transport containers to the bottom port. The bottom port has a special design for docking of different types of transport containers.

The air filters including shut-off valves, connecting pipes, cables and other pipes are installed in the shielded space above the hot cell. The in-air and exhaust air is filtered by HEPA-filters. An airlock regime divides the different compartments in order to maintain their corresponding GMP compliant clean room classes. In-air as well as gaseous or liquid matters are fed through lead-through ducts from the ceiling of the hot cells.

 

General process description

The generator is completely assembled in a clean room area as inactive and sterile generator. The generators are put on the roller conveyor under the preparation unit and transferred into the loading hot cell. The 99Mo-bulk solution is transferred via a bottom port into the dispensing hot cell. The bulk vial is opened and the bulk solution transferred into a mixing vessel where it is formulated for the loading procedure. The pH-value of this bulk solution is adjusted and it is diluted with saline to the necessary radioactive concentration of 99Mo. With help of a syringe dispenser the necessary volume for the generator loading is admeasured. This loading solution is transferred into the loading hot cell and there it is sterilized in a sterile filtration unit. At clean room class A the corresponding generator type is connected to the loading system by special connectors. The sterile loading solution is sucked through the complete assembled generator with its sterile column. After the loading process the generator is washed with saline and locked out into the preparation unit for elution check (QC) and packaging. The process steps in the dispensing hot cell and in the loading hot cell are remote operated via touch screen panel.

 

Description of the MoTc-G-4 generator

The essential part of the MoTc-G-4 generator is a sterile chromatographic column made of glass with an alumina absorbent which carries the 99Mo. The chromatographic column is surrounded by a lead shielding of 50 mm (15 kg). The generator posses an inherent sterile filter which ensures the sterility of the eluted Na[99mTc]O4. For the elution sterile vials filled with saline and sterile evacuated vials are applied. The MoTc-G-4 generator is equipped with a volume controller and two vials containing a bacteriostatic substance, which protect the sterile needles of the generator during transport and between the elution intervals. The eluted volume can be regulated by the volume controller so that a desired volume of eluent can be applied (4 to 8 ml). The accuracy of the volume of eluted Na[99mTc]O4 can be kept in the range of +/- 0.5 ml.

 

Modified Production Facilities

The small scale production facility can be offered also for the production procedure which included the steam sterilization of the loaded column. In this case the two hot cells are connected with a double door steam sterilizer. The equipment for this procedure has to be modified as adapted to the modified process.

The offer of large scale production facilities is planed for batch sizes of 150 to 200 generators. In this case a lead shielding of at least 150 mm is needed, as well as master slave manipulators and an automated transport equipment. ITD offers advisory services in order to determine the exact room and hot cell arrangement, specifically for the customer’s needs.

 

  • Standard equipment of the hot cells
  • Dispensing hot cell devices
  • Loading hot cell devices
  • Roller conveyor

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