Safety of L-proline as a stabilizer for immunoglobulin products

Abstract

Privigen^® (immune globulin intravenous [human], 10% liquid) and Hizentra^® (immune globulin subcutaneous [human], 20% liquid) are stabilized by proline. The clinical implications of administering proline-containing immunoglobulin products to patients with defects of proline metabolism have not been addressed; Privigen and Hizentra are contraindicated in these patients. Some patients with chromosome 22q11.2 deletion syndrome have elevated proline levels; however, only 3–4% of patients also have an immunodeficiency that requires IgG therapy. This review summarizes the evidence related to the safety and pharmacokinetics of proline assessed in Privigen and Hizentra preclinical and clinical studies, and subsequent implications for patients with defects in proline metabolism. Clinical data indicate that proline does not accumulate after Privigen or Hizentra treatment and is not associated with adverse events. There is no evidence to suggest that patients with defects of proline metabolism would be affected by transient elevations in plasma proline following Privigen and/or Hizentra treatment.

Keywords::

• 22q11.2 deletion syndrome
• hyperprolinemia
• intravenous immunoglobulin
• pharmacokinetics
• proline
• proline metabolism
• safety
• subcutaneous immunoglobulin

Financial & competing interests disclosure

JB Hagan has previously served as an Investigator for CSL Behring. RL Wasserman has served as a Consultant and/or an Investigator for Baxter Bioscience, CSL Behring, Talecris and Biotest. JS Baggish, MO Spycher, M Berger and E Lohrmann are employees of CSL Behring. KE Sullivan has served as a Consultant for the Immune Deficiency Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Medical writing and editorial assistance was provided by Erin P Scott, PhD, of Complete Publication Solutions, LLC. This assistance was funded by CSL Behring.