Detection of residual biocides in antibody drug conjugates for ImmunoPET imaging

Abstract

Antibody drug conjugates are comprised of monoclonal antibodies conjugated to a small molecule drug to combine the targeted delivery of the antibody with the mechanism of action of the small molecule component. One class of antibody drug conjugates is used in ImmunoPET and combines the selectivity of the antibody with a positron emission tomography imaging agent that enables imaging tumors based on binding of the antibody. As the positron emission tomography imaging reagents are limited by their radioactive half-life, they are prepared at a single patient GMP quality scale with limited advance notification of when a patient requires the dose. One aspect of this single batch manufacture is using PD-10 columns to purify the ImmunoPET agent from the excess radioactive material used in the manufacturing process. These columns are kept in a storage solution containing biocides, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, which prevent microbial growth in the column but could also adversely affect the patient if injected. We have developed a validatable HPLC-UV/MS method for the detection of biocides in formulated ImmunoPET drug product samples and formulation buffer. This method enables the demonstration of the clearance of biocides in the columns prior to use and quantitation of any residual biocides present in the drug product.