Scientific Publications by FDA Staff

Vox Sang 2011 Jul;101(1):83-9

An international collaborative study to establish the WHO 1st international standard for alpha-1-antitrypsin.

Thelwell C, Marszal E, Rigsby P, Longstaff C

Background and Objectives. The aim was to establish the 1st International Standard (IS) for alpha-1-antitrypsin (AAT) to standardise potency assignment of therapeutic products, calibrated in moles and mg active AAT in line with product labelling practice. Assigning total protein and antigen values to the IS was also investigated. Materials and Methods¿ The active concentration of four candidate AAT preparations was determined in an international collaborative study by inhibition of trypsin (calibrated by active-site titration). Total protein and antigen content were determined for each candidate using local methods and in-house standards, and a common AAT preparation. The total protein content of the IS was also determined by amino acid analysis. Potency determination of recombinant and transgenic materials against the IS was investigated in a follow-up study. Results¿ Data analysis for potency determination indicated no statistical difference between any of the candidates, or between the results for recombinant and plasma-derived products. Total protein content of the IS determined by amino acid analysis was consistent with the potency value. The variability in the total protein and antigen results for the other candidates was reduced when the data were recalculated relative to the IS. Conclusions¿ Candidate C (05/162) was established by the WHO Expert Committee on Biological Standardization (ECBS) in 2006 as the WHO 1st IS for AAT with a potency of 243¿nmoles (12·4¿mg) active inhibitor per ampoule. In 2008, ECBS approved the IS for potency determination of recombinant material and assigned a total protein and antigen value of 12·4 mg.