Intravenous Immune Globulin Shortage: Experience at a Large Children's Hospital

The current shortage of immune globulin for intravenous use (IVIG) is being attributed to several events, including an increase in off-label use, and intense Food and Drug Administration (FDA) scrutiny of product lots and manufacturing facility upgrades that result in temporary production halts.1 Additionally, there has been an increase in product recall or failure to release product because donors at risk for Creutzfeldt-Jakob disease have been identified.2 Although transmission of Creutzfeldt-Jakob disease by blood products has not been established, the FDA has recalled IVIG lots with perceived risk of contamination. This shortage has caused sufficient concern among patients and their providers to capture congressional attention.2During a recent meeting of the Health and Human Services Advisory Committee on Blood Safety and Availability, it was recommended that a systematic appraisal of off-label uses of IVIG be undertaken.3 This may assist in alleviating product shortages by discouraging use in inappropriate patient populations and by establishing priorities among approved indications. Another recommendation from that meeting was to sell product directly to hospitals and pharmacies, eliminating product handling and potential price gouging by third-party suppliers. Meanwhile, the shortage of IVIG nationwide continues and most tertiary care hospitals, especially those caring for seriously ill children, are affected.Texas Children's Hospital (TCH) is a 456-bed freestanding pediatric teaching institution affiliated with Baylor College of Medicine in Houston, Texas. Our medical staff provides primary care yearly for approximately 200 infants and children requiring administration of IVIG for serious or life-threatening medical conditions. These include primary immunodeficiency disorders, Kawasaki disease, idiopathic thrombocytopenic purpura, bone marrow transplantation, and cytopenias resulting from high-dose chemotherapy for malignancy.4 Patients with neurologic (eg, Guillain-Barré syndrome with ascending paralysis), hematologic (eg, lymphoblastic leukemia), or immunologic (eg, human immunodeficiency virus type 1) conditions, and acute bacterial infection (eg, group A β-hemolytic streptococcal myositis or necrotizing cellulitis) also may benefit from IVIG therapy.5,6To provide for the aforementioned conditions, our hospital pharmacy has for the past few years dispensed approximately 2000 g of IVIG per month. In October 1997 our stock of IVIG was decreasing rapidly, and the contracted IVIG product could no longer be supplied. We were able to secure 200 g of an off-contract product. Inquires were made, and it became apparent that there was a nationwide shortage of IVIG, that this shortage would be prolonged, and that accommodating use of 2000 g of IVIG per month would be problematic.An IVIG Task Force had been constituted earlier in the year. Anticipating a problem with the supply to our hospital, the membership of the Task Force was increased to ensure representation of key IVIG users, including physicians from the allergy and immunology, hematology and oncology, infectious diseases, neurology and general medicine services. Legal counsel and pharmacy representatives also participated. In addition to initiatives involving the medical staff, we began to seek alternative (off contract) sources of IVIG. We turned to manufacturers from whom we currently purchase other blood products. We also worked closely with local pharmaceutical sales representatives to develop relationships and assure their assistance in acquisition of IVIG. Furthermore, we identified sources of IVIG through specialty wholesalers and brokers via networking with other pharmacists in freestanding children's hospitals. IVIG either was not available or it was available at an exorbitant price.The Task Force was asked by the Pharmacy and Therapeutics Committee to determine whether patients would receive IVIG on a first-come, first-serve basis or whether IVIG would be prescribed in conformity with specific guidelines developed for its use. The Task Force agreed to create guidelines for use of IVIG at TCH and to develop a preprinted IVIG order form. IVIG would be dispensed only to patients with the following conditions:Patients who required routine monthly infusions of IVIG were required to have a serum immunoglobulin G concentration of <400 mg/dL documented before receiving an IVIG infusion. Furthermore, a list of those patients was forwarded to the pharmacy to estimate the quantity of IVIG needed per month. In the event that IVIG was not available, the patient was contacted before a scheduled clinic visit.In addition, the Task Force discussed the use of Cytogam and Respigam. Based on a review of the literature, it was determined that these specific antibody-enriched IVIG products could be used, as available, in place of standard IVIG for patients who did not meet the established guidelines criteria.5 When receiving an IVIG order, the pharmacist ascertained whether the listed indication met one of those included in the guidelines. If the indication was not listed, the pharmacist called the ordering physician to appraise him/her of the failure to meet established criteria, to discuss the need for IVIG and to suggest the possible substitution of Cytogam. If the ordering physician insisted on the use of standard IVIG for the patient, the pharmacist informed the physician of the need to obtain approval either from the director of the pharmacy or the chair of the Pharmacy and Therapeutics Committee.In December 1997 the hospital's medical staff was provided with the guidelines for IVIG use. The pharmacists were educated as to the rationale for the guidelines and the procedure for assessing appropriate use before dispensing the product. It soon became evident that the availability of Cytogam also was limited. In February 1998, the Task Force met and decided that patients ineligible for IVIG could not receive Cytogam as a substitution. For the purposes of dispensing IVIG in accordance with criteria, all IVIG products were considered therapeutically equivalent in recognition of the fact that the supply of a specific product might be limited.The medical staff was very responsive to the guidelines and, as a result, our supply of IVIG has met the need of all eligible patients. Since implementation of these guidelines, our use of IVIG has decreased by 90% and the number of patients treated with IVIG has decreased from approximately 17 to 8 per month (almost 50%; Fig 1 and Table 1). Since January 1998, our hospital also has provided IVIG for all patients with primary immunodeficiency disorders, including 10 new patients who were unable to secure IVIG through their usual care provider. Only 4 patients who did not meet guideline criteria were authorized to receive IVIG after peer review by the chair of the Pharmacy and Therapeutics Committee (Table 1).Our next steps are to determine our projected use of IVIG in the coming year and to consider whether our current guidelines for use of this product might include additional indications. Our work with the IVIG Task Force and the Pharmacy and Therapeutics Committee before the IVIG shortage enabled us to move quickly toward developing a consensus that would ensure that whatever supply of IVIG was on hand was provided to the patients with the greatest medical need. Our restriction of IVIG use during this product shortage has enabled us to dispense this product for our patients who require monthly infusions as well as for those having medical conditions for which IVIG is FDA-approved.