Sr Scientist

Purpose: THE cGMP MANUFACTURING OF ⁶⁸Ga-PSMA-HBED: USE OF THE AUTOMATED MODULAR-LAB “EAZY” WITH THE GALLIAPHARM ⁶⁸Ge/Ga GENERATOR.

Objectives: The implementation of ⁶⁸Ga-based radiopharmaceuticals in the US lags a decade compared to Europe and more recently Australia. On this work we describe the use of two components in the manufacture system for ⁶⁸Ga-peptides (Generator + automated platform) that already have a Drug Master File with FDA, in order to facilitate an eventual IND. Specifically we validated the manufacture of ⁶⁸Ga-PSMA-HBED including biological QC validation for Sterility and Bacterial Endotoxin Test in a commercial radiopharmacy (Hackensack, NJ) that routinely manufactures ¹⁸F-radiopharmaceuticals.

Methods: The PSMA-HBED peptide conjugate (cGMP grade), Modular-Lab eazy kits/reagents and the GalliaPharm Pharmaceutical GMP grade ⁶⁸Ge/⁶⁸Ga generator were purchased from Eckert & Ziegler. ⁶⁸Ga was obtained from the generator using sterile ultrapure HCl 0.1 M via an automated workflow, and purified via the NaCl method (acetone-free). The Modular-Lab eazy system comprises automated control and a single-use cartridge kit with minimal manipulation. Radiochemical Identity and purity was tested via radio-TLC using a Bioscan AR-2000 equipped with WinScan software. Protocols and Summary reports for Sterility and Bacterial Endotoxin Tests were reviewed and approved internally following standard practices.

Results: Three (3) doses of sterile ⁶⁸Ga-PSMA were produced in a single day by a single operator with an average activity concentration of 6.0 mCi/mL and average radiochemical purity of 97.1 %; average synthesis time was 12 min. No ⁶⁸Ge breakthrough was observed based on MCA analysis. BET test for this product was validated at a dilution factor of 1:40. All key quality control requirements tested were met including Filter integrity test, Appearance, Radiochemical Identity and Purity, pH, Radionuclidic Identification, Bacterial Endotoxin and Sterility.

Conclusions: Sterile doses of ⁶⁸Ga-PSMA-HBED can be produced and tested using the GalliaPharm Pharmaceutical GMP grade ⁶⁸Ge/⁶⁸Ga generator coupled with the Modular-Lab eazy system, and the workflow can be integrated in a commercial ¹⁸F-radio pharmacy. Research Support: None