Radiopharmaceutical production system and quality control system utilizing high performance liquid chromatography

A quality control module for quality control testing of a radiopharmaceutical solution, comprising:

• a pumping mechanism configured to receive a sample radiopharmaceutical solution of a purified radiopharmaceutical solution including a radioisotope, the pumping mechanism configured to separate the radiopharmaceutical solution into a first portion, a second portion, and a third portion;
• a valve mechanism in downstream communication with the pumping mechanism and configured to selectively receive at least two of the three portions of the sample radiopharmaceutical solution from the pumping mechanism;
• wherein said valve mechanism comprises a plurality of input and output valve lines;
• and
• wherein said valve mechanism is configured to rotate at a predetermined angle to change configuration from a state A to a state B for selectively directing the at least two of the three portions of the sample radiopharmaceutical solution through different predefined pairs of input and output valve lines;
• a light analyzer in communication with the valve mechanism configured to receive the first portion of the sample radiopharmaceutical solution and to determine the optical clarity of the first portion of the sample radiopharmaceutical solution;
• a high performance liquid chromatography column in communication with the valve mechanism configured to receive the first portion of the sample radiopharmaceutical solution and to separate the first portion of the sample radiopharmaceutical solution into a number of separated molecularly distinct species, the high performance liquid chromatography column in downstream communication with the light analyzer;
• a mobile phase solvent mechanism in communication with the valve mechanism, the mobile phase solvent mechanism having a mobile phase solvent reservoir configured to store a mobile phase solvent therein to selectively introduce the mobile phase solvent into the high performance liquid chromatography column through the valve mechanism to facilitate separation of the radiopharmaceutical solution into the number of separated molecularly distinct species;
• a refractive index analyzer in downstream communication with the high performance liquid chromatography column, the refractive index analyzer configured to receive the separated molecularly distinct species from the high performance liquid chromatography column and to determine the refractive index of and quantify each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the first portion of the sample radiopharmaceutical solution;
• and
• a radiation probe disposed in the quality control module, the radiation probe in communication with the valve mechanism and in upstream and downstream communication with the high performance liquid chromatography column, the radiation probe configured to measure the radioactivity of the first portion of the sample radiopharmaceutical solution upstream of and before the first portion of the sample radiopharmaceutical solution enters the high performance liquid chromatography column and to measure the radioactivity of each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the separated molecularly distinct species in the first portion of the sample radiopharmaceutical solution after the separated molecularly distinct species exit downstream of the high performance liquid chromatography column;
• wherein when the valve mechanism is in the state A, the first portion of the sample radiopharmaceutical solution is directed to the high performance liquid chromatography column;
• and
• wherein when the valve mechanism is in the state B the third portion of the sample radiopharmaceutical solution is directed to a pH detector in communication with the valve mechanism configured to receive the third portion of the sample radiopharmaceutical solution,
• the pH detector determining the pH of the sample radiopharmaceutical solution from the third portion of the sample radiopharmaceutical solution.

A quality control module for quality control testing of a radiopharmaceutical solution, comprising:

• a pumping mechanism configured to receive a sample radiopharmaceutical solution of a purified radiopharmaceutical solution including a radioisotope, the pumping mechanism configured to separate the sample radiopharmaceutical solution into a plurality of portions;
• a valve mechanism in downstream communication with the pumping mechanism and configured to receive selected ones of the plurality of portions of the sample radiopharmaceutical solution from the pumping mechanism;
• wherein said valve mechanism comprises a plurality of input and output valve lines;
• wherein said valve mechanism is configured to rotate at a predetermined angle to change configuration from a state A to a state B for selectively directing the selected ones of the plurality of portions of the sample radiopharmaceutical solution through different predefined pairs of input and output valve lines;
• a light analyzer in communication with the valve mechanism configured to receive a first portion of the plurality of portions of the sample radiopharmaceutical solution and to determine the optical clarity of the first portion of the sample radiopharmaceutical solution;
• a high performance liquid chromatography column in communication with the valve mechanism configured to receive the first portion of the plurality of portions of the sample radiopharmaceutical solution and to separate the first portion of the plurality of portions of the sample radiopharmaceutical solution into a number of separated molecularly distinct species, the high performance liquid chromatography column in downstream communication with the light analyzer;
• a mobile phase solvent mechanism in communication with the valve mechanism, the mobile phase solvent mechanism having a mobile phase solvent reservoir configured to store a mobile phase solvent therein to selectively introduce the mobile phase solvent into the high performance liquid chromatography column through the valve mechanism to facilitate separation of the radiopharmaceutical solution into the number of separated molecularly distinct species;
• a refractive index analyzer in downstream communication with the high performance liquid chromatography column, the refractive index analyzer configured to receive the separated molecularly distinct species from the high performance liquid chromatography column and to determine the refractive index of and quantify each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the first portion of the plurality of portions of the sample radiopharmaceutical solution;
• and
• a radiation probe disposed in the quality control module, the radiation probe in communication with the valve mechanism and in upstream and downstream communication with the high performance liquid chromatography column, the radiation probe configured to measure the radioactivity of the first portion of the plurality of portions of the sample radiopharmaceutical solution upstream of and before the first portion of the plurality of portions of the sample radiopharmaceutical solution enters the high performance liquid chromatography column and to measure the radioactivity of each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the separated molecularly distinct species in the first portion of the plurality of portions of the sample radiopharmaceutical solution after the separated molecularly distinct species exit downstream of the high performance liquid chromatography column.

A quality control module for quality control testing of a radiopharmaceutical solution, comprising:

• a pump assembly adapted to be coupled to a quality-control line from a radiopharmaceutical production system, the pump assembly configured to receive a sample radiopharmaceutical solution of a purified radiopharmaceutical solution including a radioisotope, the pump assembly configured to separate the sample radiopharmaceutical solution into a first portion, a second portion, and a third portion;
• at least one pathway coupled to the pump assembly, the pump assembly configured to selectively pump a portion of the sample radiopharmaceutical solution through the at least one pathway to selectively perform at least one test on the sample radiopharmaceutical solution;
• a valve mechanism in downstream communication with the pump assembly, the valve mechanism configured to selectively receive and direct at least two of the three portions of the sample radiopharmaceutical solution from the pump assembly, the valve mechanism comprising:
• a plurality of valve fluid pathways defined therein;
• wherein the valve mechanism is configured to rotate at a predetermined angle to change configuration from a state A to a state B;
• and
• at least two pairs of inlets and outlets selectively formed by the plurality of valve fluid pathways depending on selective positioning of the valve mechanism, the quality control module having a plurality of valve lines in selective communication with the valve mechanism, the valve mechanism being selectively positioned to align at least two pairs of inlets and outlets to a corresponding select two pairs of valve lines, each pair of select valve lines directing one of the three portions of the sample radiopharmaceutical solution into a selective predetermined processing flow path;
• a light analyzer in communication with the valve mechanism configured to receive the first portion of the sample radiopharmaceutical solution and to determine the optical clarity of the first portion of the sample radiopharmaceutical solution;
• a high performance liquid chromatography (HPLC) column in communication with the valve mechanism configured to receive the first portion of the sample radiopharmaceutical solution and to separate the first portion of the sample radiopharmaceutical solution into a number of separated molecularly distinct species, the HPLC column in downstream communication with the light analyzer;
• a mobile phase solvent mechanism in communication with the valve mechanism, the mobile phase solvent mechanism including:
• a mobile phase solvent reservoir configured to store a mobile phase solvent therein;
• a degasser in downstream communication with the mobile phase solvent reservoir, the degasser configured to remove dissolved gases in the mobile phase solvent;
• and
• a HPLC pump in downstream communication with the degasser, the HPLC pump configured to selectively draw the mobile phase solvent through the degasser from the mobile phase solvent reservoir and selectively introduce the mobile phase solvent into the HPLC column through the valve mechanism to facilitate separation of the sample radiopharmaceutical solution into the number of separated molecularly distinct species, the valve mechanism configured to also selectively receive and direct the mobile phase solvent through a pair of select valve lines at each state of the valve mechanism and directing the same into a selective predetermined processing flow path towards the HPLC column;
• a refractive index analyzer in downstream communication with the HPLC column, the refractive index analyzer configured to receive the separated molecularly distinct species from the HPLC column and to determine the refractive index of and quantify each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the first portion of the sample radiopharmaceutical solution;
• and
• a radiation probe disposed in the quality control module, the radiation probe in communication with the valve mechanism and in upstream and downstream communication with the HPLC column, the radiation probe configured to measure the radioactivity of the first portion of the sample radiopharmaceutical solution upstream of and before the first portion of the sample radiopharmaceutical solution enters the HPLC column and to measure the radioactivity of each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the separated molecularly distinct species in the first portion of the sample radiopharmaceutical solution after the separated molecularly distinct species exit downstream of the HPLC column;
• wherein when the valve mechanism is in the state A, the first portion of the sample radiopharmaceutical solution is directed to the HPLC column;
• and
• wherein when the valve mechanism is in the state B, the third portion of the sample radiopharmaceutical solution is directed to a pH detector in communication with the valve mechanism configured to receive the third portion of the sample radiopharmaceutical solution,
• the pH detector determining the pH of the sample radiopharmaceutical solution from the third portion of the sample radiopharmaceutical solution.