Technetium Tc 99m Albumin Aggregated Injection

Albumins,blood serum,metastable technetium-99labeled.
»Technetium Tc 99m Albumin Aggregated Injection is a sterile,aqueous suspension of Albumin Human that has been denatured to produce aggregates of controlled particle size that are labeled with 99mTc.It is suitable for intravenous administration.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 99mTc as aggregated albumin expressed in megabecquerels (microcuries or millicuries)per mLat the time indicated in the labeling.It may contain antimicrobial,reducing,chelating,and stabilizing agents,buffers,and nonaggregated albumin human.Other chemical forms of radioactivity do not exceed 10percent of the total radioactivity.Its production and distribution are subject to federal regulations (see Biologics á1041ñand Radioactivity á821ñ).
Packaging and storage— Preserve in single-dose or in multiple-dose containers,at a temperature between 2and 8.
Labeling— Label it to include the following,in addition to the information specified for Labelingunder Injections á1ñ:the time and date of calibration;the amount of 99mTc as aggregated albumin expressed as total megabecquerels (millicuries or microcuries)and concentration as megabecquerels (microcuries or millicuries)per mLat the time of calibration;the expiration date;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 99mTc is 6.0hours.In addition,the labeling states that it is not to be used if clumping of the albumin is observed and directs that the container be agitated before the contents are withdrawn into a syringe.
Particle size— Shake the Injection well,and determine the dimension of not less than 100particles of a representative test specimen,using a suitable counting chamber,such as a hemacytometer grid,by optical microscopy.Not less than 90.0%of the observed aggregated particles have a diameter between 10µm and 90µm,and none of the observed particles have a diameter greater than 150µm.
Bacterial endotoxins á85ñ— The limit of endotoxin content is not more than 175/VUSP Endotoxin Unit 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 3.8and 8.0.
Radiochemical purity— Place a measured volume of Injection,appropriately diluted,such that it provides a count rate of about 20,000counts per minute,about 25mm from one end of a 25-×300-mm strip of chromatographic paper (see Chromatography á621ñ),and allow to dry.Develop the chromatogram over a period of about 3to 4hours by ascending chromatography,using dilute methanol (7in 10),and air-dry.Determine the radioactivity distribution by scanning the chromatogram with a suitable collimated radiation detector.Not less than 90%of the total radioactivity is found as aggregated albumin (at the point of application).
Place a measured volume of Injection in a centrifuge tube,and determine the net radioactivity in a suitable counting assembly.Centrifuge at approximately 2000rpm for 5to 10minutes.Separate the supernatant by aspiration,and determine its net radioactivity in a suitable counting assembly.Determine the percentage of radioactivity in the supernatant taken by the formula:
100(A/B),
in which Ais the net radioactivity,in counts per minute,in the supernatant aliquot,and Bis the total radioactivity,in counts per minute,in the tube prior to centrifugation.Not more than 10.0%of the radioactivity is found in the supernatant,which contains soluble and dispersed radiochemical impurities,following centrifugation.
Protein concentration—
Test preparation— Transfer 2.0mLof Injection to a suitable centrifuge tube,and centrifuge at about 2000rpm for 5to 10minutes.Decant the supernatant,and add 2.0mLof Sodium Chloride Injection to wash the centrifuged aggregate.Centrifuge again at 2000rpm for 5to 10minutes,decant the supernatant,and add 2.0mLof Sodium Chloride Injection.
Standard preparation— To a second test tube add 2.0mLof a solution containing 2.0mg of Albumin Human per mLin 0.9percent sodium chloride solution.
Procedure— To a third test tube add 2.0mLof Sodium Chloride Injection to provide a blank.To each of the three tubes containing the Test preparation,Standard preparation,and blank,add 4.0mLof biuret reagent TS,mix,and allow to stand for 30minutes,accurately timed,for maximum color development.Additional mixing or slight heating may be required to dissolve the aggregated albumin completely,but the Test preparation,Standard preparation,and blank are to be treated identically.Determine the absorbances of the solutions from the Test preparationand the Standard preparationin 1-cm cells at the wavelength of maximum absorbance at about 540nm,with a suitable spectrophotometer,against the blank.Calculate the quantity,in mg,of aggregated albumin in each mLof the Injection taken by the formula:
2(AU/AS),
in which AUand ASare the absorbances of the solutions from the Test preparationand the Standard preparation,respectively.The protein concentration is not more than 1mg,as aggregated albumin,per 37MBq (1mCi)of Tc 99m at the time of administration.
Biological distribution— Inject intravenously between 0.075MBq and 0.75MBq (2µCi and 20µCi)of Injection,in a volume not exceeding 0.2mL,into the caudal vein of each of three 20-to 25-g mice.[NOTE—Other animal species,such as Sprague-Dawley rats (weighing 100g to 175g),may be used.]Five to 10minutes after the injection,sacrifice the animals,and carefully remove the liver and lungs of each by dissection.Place each organ and the remaining carcass in separate,suitable counting containers,and determine the radioactivity,in counts per minute,in each container with an appropriate detector,using the same counting geometry.Determine the percentage of radioactivity in the liver and the lungs taken by the formula:
100(A/B),
in which Ais the net radioactivity,in counts per minute,in the organ,and Bis the total radioactivity,in counts per minute,in the lungs,liver,and carcass.Not less than 80.0%of the radioactivity is found in the lungs,and not more than 5.0%of the radioactivity is found in the liver,in not less than two of the animals.
Other requirements— It meets the requirements of the tests for Radionuclide identificationand Radionuclidic purityunder Sodium Pertechnetate Tc 99m Injection.It meets the requirements under Injections á1ñ,except that it may be distributed or dispensed prior to completion of the test for Sterility,the latter test being started on the day of final manufacture,and except that it is not subject to the recommendation on Volume in Container.
Assay for radioactivity á821ñ— Using a suitable counting assembly (see Selection of a Counting Assembly),determine the radioactivity,in MBq (µCi)per mL,of 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 1850
Phone Number:1-301-816-8305