Dealing with a critical national shortage-Approaches to triaging immune globulin supply in pediatric hematology and oncology

• Type of Material: Article
• Authors: Holly J Edington, Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta; Kathryn Sutton, Emory University; Carolyn Bennett, Emory University; Shanmuganathan Chandrakasan, Emory University; Jennifer Sterner-Allison, Childrens Healthcare Atlanta; Sharon Castellino, Emory University
• Language: English
• Date: 2020-04-24
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/pbc.28260
• Title of Journal or Parent Work: PEDIATRIC BLOOD & CANCER
• Volume: 67
• Issue: 7
• Start Page: e28260
• End Page: e28260
• Grant/Funding Information: This study is supported by TL1 Postdoctoral Clinical & Translational Research Training Grant TL1TR002382 and National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: Science & Technology; pediatric use; Life Sciences & Biomedicine; Oncology; CHEMOTHERAPY; Pediatrics; IVIG; LEUKEMIA; INTRAVENOUS IMMUNOGLOBULIN; Hematology; CHILDREN; immunodeficiency; immunomodulation

Abstract

The United States has experienced a shortage of immunoglobulin since late 2018. Both intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG), which originate from a common plasma pool, have been affected. In August 2019, the U.S. Food and Drug Administration (FDA) confirmed the critical nature of the shortage and its impact on patient care.1 Initially the FDA named two manufacturers, Bio Products Laboratory and Baxalta, who could not meet high demands that exceeded manufacturing plans and available inventory.2 An update from the American Society of Hospital Pharmacists in February 2020 stated that 6 of 7 manufacturers could not meet demands; this impacts 9 of 12 commercially available IVIG products and 7 of 8 SCIG products.3 Together this comprises ~90% of the market share of immunoglobulin.4 While the immunoglobulin shortage in 1998 was attributed to a combination of increased demand, manufacturing challenges, and product recalls over a concern for Creutzfeldt-Jakob disease transmission,5 there is no specific attribution for the current shortage. Drivers of increased demand are likely multifactorial (Figure 1). Though adult patients utilize the majority of immunoglobulin products, IVIG and SCIG play a critical role in immunomodulation and immunoglobulin replacement in pediatrics. The half-life of IVIG is generally accepted to be 3–4 weeks, but can vary based on individual pharmacokinetics.6 Dosing for immunomodulation and replacement of secondary hypogammaglobulinemia varies by disease. Additionally, as immunoglobulin G (IgG) norms fluctuate during early childhood and into adulthood, the ideal threshold level for replacement of secondary hypogammaglobulinemia remains elusive.