The entire production workflow is developed in accordance with EU cGMP and GAMP5 guidelines, with particular attention to operator safety, process sterility, and product integrity.
The line is designed as an integrated ecosystem of isolators and functional modules, capable of covering all critical stages of RLT production, from preparation to dispensing.
All software architectures required for operating the equipment comply with FDA CFR 21 Part 11 regulations , ensuring high safety standards while maintaining data integrity.
Let’s now take a closer look at the workflow of this RLT Production Line.
Once the tests have been successfully completed, the materials are loaded into the antechamber (SAS-LAF).
Here, an initial phase of handling and preparation of consumables takes place, which includes:
Before being transferred to the main chamber, the entire system undergoes a decontamination cycle using hydrogen peroxide via HYPER technology.
This step is crucial to ensuring a sterile environment that is ready for production.
The process consists of four main stages:
Once decontamination is complete, the materials are transferred from the SAS-LAF to the main chamber (FLEX), thereby maintaining sterile and contained conditions.
This stage marks the transition from preparation to actual production, where precision, repeatability, and control become key factors.
Once the materials have been transferred to the main chamber (FLEX), the process enters its most critical phase: the production and filling of the radiopharmaceutical.
The CRP Compact system handles the semi-automatic filling of single-dose or multi-dose vials, ensuring:
The CRP Compact system is capable of semi-automatically evaluating the total activity of the Lu177-based radiopharmaceutical coming from the synthesis module, automatically calculate the dilution volume required to achieve the target concentration of the radiopharmaceutical in order to ensure compliance with the standards defined by the customer or hospital for filling the final vial.
The dosing of radiopharmaceuticals under cGMP conditions is a sterile process, which means that radiopharmaceuticals must be handled via a sterile, single-use fluid path, using biocompatible materials suitable for this purpose.
For a process to be defined as sterile, it must include final filtration. For this reason, a 0.22 µm membrane filter is included to remove potential impurities from the fluid before it enters the Lu177-based radiopharmaceutical vial. In this regard, the dispenser must automatically verify the integrity of this filter before releasing the pharmaceutical batch; therefore, a specific procedure must be established for its automatic testing.
Dispensing accuracy is ensured by an analytical balance, which measures the volume of fluid transferred with extreme precision.
To ensure safety and compliance with GMP standards for radiopharmaceutical production, the vials—once filled with the radiopharmaceutical and sealed—must undergo additional tests and procedures to verify their compliance.
This post-processing step can be carried out using equipment and standards specific to the various radiopharmacies, or by using a specially designed shielded isolator developed by Tema Sinergie:the Inspection Module.
Thanks to the Inspection Module, each vial—inside the shielded lead pot (to ensure safe handling)—is processed by automatically performing the following:
The line installed at IRST IRCCS in Meldola is not only an advanced technological solution but also a flexible model designed to evolve alongside the needs of Radioligand Therapy.
The project reflects Tema Sinergie’s approach to developing modular and scalable solutions capable of adapting to the varying levels of automation, productivity, and integration required by different centers.
Key benefits include:
The project implemented at IRST Meldola represents a significant example of innovation applied to modern radiopharmacy in Italy.
We are proud to have supported a center of excellence in our region, recognized at the European level and among the first facilities authorized and operational in the use of beta-emitting radiopharmaceuticals for cancer treatment.
On the one hand, this production line serves as a concrete example of how an integrated production line can support:
In an industry where precision and safety are not optional but essential, solutions like this become true enablers of innovation.
On the other hand, it highlights how the integration of clinical expertise and advanced technological solutions demonstrates the potential to build an infrastructure capable of supporting therapeutic innovation while keeping the patient at the center.
The GMP Production Line for RLT offers complete control over every stage of the process and enables centers of excellence, such as the IRST IRCCS in Meldola, to confidently tackle the challenges of nuclear medicine in the future.
At the same time, the modular and scalable approach we adopt for our production lines enables us to develop even more advanced architectures in terms of automation, digital integration, and production capacity, supporting the growth of Radioligand Therapy on an international level.