Indium In 111Ibritumomab Tiuxetan Injection
»Ibritumomab Tiuxetan is the immunoconjugate resulting from a stable thiourea covalent bond between the monoclonal antibody Ibritumomab and the linker-chelator tiuxetan [N-[2-bis(carboxymethyl)amino]-3-(p-isothiocyanatophenyl)propyl]-[N-[2-bis(carboxymethyl)amino]-2-(methyl)ethyl)glycine.This chelate provides a high-affinity,conformationally restricted chelation site for Yttrium-90and Indium-111.The approximate molecular weight of Ibritumomab Tiuxetan is 148kD.
Ibritumomab is a murine IgG1kappa monoclonal antibody directed against the CD20antigen,which is found on the surface of normal and malignant Blymphocytes.Ibritumomab is produced in Chinese hamster ovary cells and is composed of two murine gamma 1heavy chains of 445amino acids each and two kappa light chains of 213amino acids each.
Indium In 111Ibritumomab Tiuxetan Injection is a sterile,nonpyrogenic preparation of the immunoconjugate of ibritumomab and tiuxetan that is labeled with 111In and is suitable for intravenous administration.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 111In as the ibritumomab complex,expressed in megabecquerels (or millicuries)per mLat the time indicated in the labeling.It may contain buffers and stabilizers.It contains no antimicrobial agents.Other chemical forms of radioactivity do not exceed 5percent of the total radioactivity.The immunoreactive fraction,as determined by a validated method,is not less than 90percent.
Packaging and storage— Preserve in single-dose containers,and store in a refrigerator for not more than 12hours.[NOTE—Translucent protein particles may develop,which are removed by filtration prior to administration using a 0.22micron low-protein-binding filter.]
Labeling— Label it to include the following in addition to the information specified for LabelingunderInjections á1ñ:the time and date of calibration;the amount of 111In Ibritumomab Tiuxetan as total MBq (or mCi)and concentration of MBq (or mCi)per mLat the time of calibration;the expiration date and time;the storage temperature;and the statement,“Caution—Radioactive Material.”The labeling indicates that,in making dosage calculations,correction is to be made for radioactive decay,and also indicates that the radioactive half-life of 111In is 67.3hours.
Bacterial endotoxins á85ñ— The limit of endotoxin content is not more than 175/VUSP Endotoxin Units per mLof the Injection,when compared with the USP Endotoxin RS,in which Vis the maximum recommended total dose,in mL,at the expiration date or time.
pHá791ñ: between 5.5and 7.5.
Radiochemical purity—
Absorbent: 1-×8-cm instant silica gel strip.
Test solution: the Injection.
Application volume: 10µL.
Developing solvent system: 0.9%sodium chloride solution.
Procedure— Proceed as directed for Thin-Layer Chromatographyunder Chromatography á621ñby ascending chromatography.Determine the distribution of radioactivity on the chromatogram by scanning with a suitable collimated radiochromatogram strip scanner,and determine the percentage of radiochemical purity of the test specimen.Not less than 95%of the In 111activity is present as a band between the RFvalues of 0and 0.1.
Other requirements— It meets the requirements for Radionuclide identificationand Radionuclidic purityunder Indium In 111Chloride Solution.It meets also the requirements under Injections á1ñ,except that the radioactive component may be distributed or dispensed prior to completion of the test for Sterility,the latter test being started on the date of manufacture.
Assay for radioactivity á821ñ— Using a suitable counting assembly (see Selection of a Counting Assembly),determine the total radioactivity,in MBq (or µCi)of the unshielded Injection by use of a calibrated system.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1009
Phone Number:1-301-816-8305