GMP Standard Synthesis Hot Cell for Radiopharmaceutical Production Line with

This is the most critical feature. The hot cell must effectively shield the high-energy gamma rays or neutrons emitted by the radionuclides inside.

• Materials:

  Typically made of high-density lead (Pb) bricks or plates as the primary shielding material. Lead glass (for viewing windows) and steel (for structural support and enhanced shielding) are also often used.

• Thickness:

  The thickness of the shielding walls is precisely calculated based on the type of radionuclide being handled (e.g., F-18, Ga-68, Lu-177) and its activity. The thickness can range from a few centimeters to several tens of centimeters to ensure the radiation dose rate on the hot cell's external surface is reduced to well below safe regulatory limits (e.g., typically far below 2.5 μSv/h).

• Containment:

  The hot cell is a highly sealed system to prevent the leakage of radioactive aerosols or volatile substances into the external environment.

• Negative Pressure System:

  The interior of the hot cell maintains a negative pressure (i.e., the internal air pressure is lower than the pressure in the surrounding room). This ensures that even if a minor leak occurs, air flows from the outside into the hot cell, preventing any contaminants from escaping.

• HEPA Filtration:

  All air exhausted from the hot cell must pass through High-Efficiency Particulate Air (HEPA) filters, often multiple stages, to capture any potentially radioactive particles. For volatile radionuclides (e.g., I-131), specialized activated carbon filters are also used.

Since direct hand contact with internal items is impossible, hot cells are equipped with various remote handling tools:

• Manipulators:

  The most classic are master-slave manipulators, where the operator moves the "master" arms outside the cell, and the "slave" arms inside precisely replicate all movements. Modern hot cells more commonly use electric-powered manipulators controlled by joysticks or touchscreens.

• Full Automation Systems:

  This is the mainstream trend in modern radiopharmaceutical production. The entire synthesis process (e.g., heating, cooling, liquid transfer, purification) is performed by computer-program-controlled automated modules (e.g., synthesizers, Chemical Process Modules - CPM). The operator simply starts the process via a software interface, drastically reducing human intervention, error, and improving repeatability and yield.

Radiopharmaceuticals are injected into humans and must meet stringent standards for being sterile and pyrogen-free.

• Internal Environment:

  The hot cell interior is designed as a clean environment, typically meeting Grade C or A (ISO Class 7 or 5) cleanliness standards.

• Transfer Systems:

  Equipped with dedicated pass-through boxes for introducing materials and reagents and removing the final product. These pass-throughs often have interlocking mechanisms and ultraviolet (UV) lights to prevent cross-contamination and for surface decontamination.

• Surface Materials:

  Internal walls have smooth, seamless, and easily cleanable surfaces (e.g., stainless steel) resistant to frequent disinfection with cleaning agents.

To allow operators a clear view of the internal processes:

• Lead Glass Window:

  Made of special lead glass containing lead oxide, which provides necessary transparency while offering radiation shielding equivalent to the surrounding lead walls. The windows are usually multi-layered and very thick.

The hot cell integrates all necessary utility interfaces for production:

• Electrical:

  Powers internal instruments, manipulators, lighting, and sockets.

• Pneumatic:

  Supplies compressed air or inert gases (e.g., nitrogen) for driving pneumatic valves, drying reagents, etc.

• Vacuum:

  Used for filtration or liquid transfer.

• Cooling/Ventilation:

  Contains independent cooling systems (e.g., cold traps) and internal circulation fans to remove heat generated by chemical reactions, maintaining a stable temperature for internal instruments and reagents.

• Radiation Monitoring:

  Built-in radiation detectors continuously monitor internal radiation levels.

• Pressure Monitoring:

  Continuously monitors and displays the internal negative pressure status; an alarm is triggered if pressure is lost.

• Temperature/Smoke Monitoring:

  Equipped with temperature and smoke sensors to prevent safety incidents caused by overheating or fire.

• Interlocks:

  Doors, pass-through boxes, etc., are equipped with safety interlocks to prevent them from being opened at the wrong time, which could cause radiation leakage.