Standardization of a method for freeze-drying of antibodies as ready to use therapeutic radiopharmaceuticals

Abstract

Monoclonal antibodies (mAbs) are currently assessed as a significant and growing class of drugs of biological origin. The goal of our investigation was to introduce and standardize an available protocol for freeze-drying a formulation of conjugated antibody as a ready-to-use radiopharmaceutical product with therapeutic potential and to assess the stability and integrity of the obtained product. For that purpose, we introduced a shortened two-day protocol for freeze-drying of rituximab-1B4M-DTPA immunoconjugate and compared the appearance of the freeze-dried product with the products of a previously reported three-day freeze-drying protocol. The qualitative assessment of the final product was performed by infrared spectroscopy of the freeze-dried cake powders, measurement of the reconstitution times of the freeze-dried cakes and comparison of gel filtration profiles of obtained products. Considering the obtained results, we can conclude that the two days freeze-drying protocol is superior to the three days protocol based on the time and energy saved. More studies on the optimization and control of the critical freeze-drying process parameters and the critical formulation attributes are also encouraged, as well as the optimization of the conjugation and labelling protocols. None of the freeze-drying protocols produced detectable fragments. The product appearance, reconstitution times and opacity on reconstitution were similar and also the ATR/FTIR spectra demonstrating that the two freeze drying protocols yield products of similar quality.