Phase I Comparability of Recombinant Human Albumin and Human Serum Albumin

Abstract

Recombinant human albumin (rHA) is a highly purified animal-, virus-, and prion-free product developed as an alternative to human serum albumin (HSA), to which it is structurally equivalent. The present investigation compared the safety, tolerability, and pharmacokinetics/pharmacodynamics of rHA with HSA. Two double-blind, randomized trials were performed in healthy volunteers using intramuscular (IM) and intravenous (IV) administration. The IM trial included 500 volunteers, each receiving 5 repeat doses of 5 mg (100 subjects), 15 mg (100 subjects), or 65 mg (300 subjects) of rHA or HSA. Thirty volunteers participated in the IV trial, each receiving ascending doses (10 g, 20 g, and 50 g) of either rHA or HSA. In both trials, all adverse events were recorded and conventionally classified; potential allergic responses were also monitored. Blood samples were taken in both studies to test for IgG or IgE antibodies against test products and potential impurities. For the IV study, pharmacokinetic/pharmacodynamic assessments were performed, including measurement of serum albumin, colloid osmotic pressure, and hematocrit pre- and postinfusion. Nine subjects in the IM study (4 recipients of rHA and 5 of HSA) reported drug-related, potentially allergic events; all but 2 of these were skin related. No serious or potentially allergic events were reported with either product in the IV study. There was no immunological response to either product, and dose level did not influence the study outcomes. Serum albumin, colloid osmotic pressure changes, and hematocrit ratio were as expected, with no differences between rHA and HSA. rHA and HSA exhibited similar safety, tolerability, and pharmacokinetic/pharmacodynamic profiles, with no evidence of any immunological response.

Human serum albumin: From bench to bedside

“…Indeed, even at a rHSA purity of 99.999%, 1 mg of impurities injected by the administration of 100 g of rHSA represents enough contaminating material to elicit an adverse immune response (Ohtani et al, 1998;Kobayashi, 2006). rHSA purified from P. pastoris is structurally identical to plasma-derived HSA (pdHSA) (Ikegaya et al, 1997;Kobayashi, 2006), and has shown comparable safety, tolerability, pharmacokinetics, and pharmacodynamics (Bosse et al, 2005;Kobayashi, 2006). In 2007, rHSA expressed in P. pastoris has been approved as a medicine, and in 2008 this rHSA has been launched in Japan for therapeutic purpose (Murasugi, 2010).…”

Sulfenic acid—A key intermediate in albumin thiol oxidation

“…Recombinant HSA has been successfully produced using different expression systems, most significantly the yeast Pichia pastoris. This recombinant albumin shows comparable safety and efficacy as blood derived albumin [20][21][22]. The availability of recombinant albumin has opened the way to novel pharmaceutical applications, such as a fusion product of albumin and interferon, currently being assessed in phase III clinical trials for the treatment of hepatitis C [19,23].…”

Allergy to human seminal fluid: Cross-reactivity with dog dander

“…Can f 3, dog albumin, which is an important allergen for up to 35% of patients with dog epithelium allergy, has been demonstrated to show IgE cross-reactivity with other serum albumins, such as cat, mouse, chicken, and rat albumin, and significantly with human albumin as well. [16][17][18][19] We identified and characterized by means of MS the responsible allergen in the HSP anaphylactic reaction here studied, and it turned to be the PSA, a kallikrein protein with serine protease activity that is present at levels of 0.5 to 2 mg/ mL in HSP. The possible prostate origin of the HSP allergens, confirmed in our study by means of allergen characterization, was proposed by Levine et al 20 several years ago.…”