A novel “in-line radiolabelling” method for large scale protein labeling: Indian experience

An Iodine-131 radiolabelled chTNT-1/B monoclonal antibody (“Drug Product”) that targets the necrotic core of any solid tumor is currently in clinical trials for the treatment of brain tumors in the USA. Unlike other tumors, brain tumors present special challenges for the development of effective therapies: such as, the maximum volume of drug that can be administered without causing edema or the maximum amount of cations (i.e. sodium and potassium) in the drug that can be tolerated by a patient. Scientists at Peregrine Pharmaceuticals Inc., and their collaborators, have developed a novel approach to manufacture this radiopharmaceutical with the following parameters:

A procedure for radiolabelling chTNT-1/B antibody to produce desired amounts of Drug Product for intratumoral administration to patients within 5 days of radiolabelling;

Keep the volume of final Drug Product to not more than 9 mL per dose;

Ensure that the potency of I-131 labelled chTNT-1/B and the percentage of intact antibody monomer remains stable, in frozen condition, for at least 5 days;

Ensure the free Iodine content remains as low as possible, when the product is frozen for at least 5 days; and

Ensure, not only Drug Product remains stable when thawed 5 days after manufacture, Drug Product remains stable at room temperature for up to 24 hours thereafter.

M/s Peregrine Pharmaceuticals have entered into a collaborative work with BRIT, India for transfer, to BRIT, of Peregrine's scaled-up in-line radiolabelling process for simultaneous production of multiple patient dosages of the Drug Product which brings down the overall production costs compared to conventional radiolabelling methods. M/s Peregrine Pharmaceuticals Inc, USA plans to manufacture the product and carry out clinical trials in India. Presently the process setup and initial batches are being manufactured at BRIT and data is being accumulated for presentation to regulatory authorities.