The Food and Drug Administration (FDA) is issuing this notice in order to update an earlier correspondence and revise our previous advice regarding the safety of albumin administration in critically ill patients. This action is being taken following FDA’s review of recent studies on the safety of albumin, and is consistent with recommendations made on March 17, 2005 by members of the Blood Products Advisory Committee (BPAC).  In May 2004, the New England Journal of Medicine published the SAFE study, the largest randomized controlled trial to date to have addressed the safety of albumin (N Engl J Med 2004;350:2247-56). In this trial, 6997 critically ill subjects were randomized to receive either 4% albumin or normal saline for the treatment of hypovolemia.  The results indicated that for patients in the general ICU population requiring fluid resuscitation, the mortality rate of those who receive albumin is the same as for those who receive saline (relative risk of mortality 0.99; 95% confidence interval: 0.91, 1.09). Secondary analyses of pre-specified subgroups of patients with ARDS, severe sepsis, and trauma were consistent overall with this finding. Two additional findings deserve mention. First, results of an exploratory analysis of trauma patients with concomitant traumatic brain injury showed increased mortality in the albumin treatment arm (relative risk of mortality 1.36; 95% confidence interval 0.99, 1.86). Second, a higher survival rate was observed in the albumin treated patients with severe sepsis, but since this finding was not statistically significant (p=0.09), its clinical significance remains uncertain.