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Objective: This study assessed whether trials to investigate the effect of hepatic impairment on the pharmacokinetics of therapeutic proteins (TPs), which are conducted for small molecule drugs, are necessary. Methods: The product labeling for 91 TPs that have been approved by the US Food and Drug Administration were reviewed. A PubMed search was also conducted to identify completed studies that assessed the effect of hepatic impairment on the pharmacokinetics of TPs. Biologic License Applica-tions were subsequently reviewed to gather further descriptions of the trials conducted in patients with hepatic impairment and data analyses. Results: No dedicated pharmacokinetics trials were conducted in patients with hepatic impairment for these approved TPs, but subgroup (n = 2 [2.2%]) or population (n = 5 [5.5%]) pharmacokinetic analyses were performed for 7 TPs. The pharmaco-kinetics of these proteins were not affected by the hepatic dysfunction, with the exception that the clearance of drotrecogin alfa seemed 25% higher in patients with hepatic impairment than in patients without hepatic impairment; however, no dose re-duction was recommended. Thus, the effect of hep-atic impairment on the pharmacokinetics of TPs is unclear based on the limited analyses completed to date. Conclusions: A dedicated pharmacokinetics trial for TPs in patients with hepatic impairment is not necessary. Recognizing that the data are very limited, it would be important to continue collecting phar-macokinetic data of TP in patients with hepatic impairment and using population pharmacokinetic analyses to evaluate the effect of hepatic impairment on the pharmacokinetics of TP. (Clin Ther. 2013;35:1444-1451) Published by Elsevier HS Jour-nals, Inc. [ABSTRACT FROM AUTHOR]