Shortfall in immune globulin supplies looms
Supplies of immune globulin products are shrinking nationwide, and no one knows why. The Food & Drug Administration is investigating the problem, while health-care professionals try to prioritize patients and locate alternatives. There are shortages of both intravenously injected (IVIG) and intramuscularly injected (IMIG) immune globulin products, although the IVIG shortage is more acute--and more mysterious. Officials and industry believe the IMIG shortage, caused by production delays, is temporary, and they are concentrating instead on the IVIG shortfall.
"We still don't have any indication of the severity of the IVIG shortage," said Jason Bablek, director of regulatory affairs for the International Plasma Products Industry Association in Washington, D. C. Bablek believes a major reason could be the increasing use of IVIG. "Basically, it's just being used more than it can be produced at the moment." IVIG is indicated for a range of immunorelated diseases but has enjoyed off-label popularity for more than 50 other conditions, including chronic fatigue syndrome and several neurological disorders.
Other factors for the IVIG shortage may be production delays among the nation's six manufacturers, as well as recalls fueled by fears over the spread of Creuzfeldt-Jakob disease (CJD). In 1997, the FDA ordered more than a dozen recalls of IVIG products after learning of donors with CJD or at risk for developing it, even though "there is no scientific proof that CJD can be transmitted through blood or blood products," according to Bablek. Manufacturers willingly comply with the FDA's conservative policy "just in case."
Until the extent and causes of the shortage are known, it's anyone's guess when it will be over. But there may be a silver lining for one manufacturer. MedImmune Inc., of Gaithersburg, Md., said recent studies have shown its CytoGam (cytomegalovirus [CMV] immune globulin intravenous [human]) to be comparable to IVIG therapy for a number of conditions. CytoGam is indicated for attenuation of primary CMV disease associated with kidney transplantation.
Medimmune's director of medical information, Robert J. Fuentes, Pharm.D., said that as the shortage becomes more severe, more practitioners are substituting CytoGam--despite its significantly higher cost. "Our sales almost quadrupled for December." He has been deluged with calls from hospital R.Ph.s and others asking about IVIG/CytoGam comparisons. At press time, Fuentes said that demand was continuing to rise and that all orders after Jan. 6 would be on a one-month backorder.
While the IVIG shortage appears to have been sudden, problems with the nation's IMIG supply are more chronic. "There's been a shortage of IMIG in this country now for over two years. [The level of] production is such that by the time a particular lot is ready, we've pretty much exhausted the supply of the previous lot," explained Beth Bell, M.D., M.P.H., medical epidemiologist at the hepatitis branch of the Centers for Disease Control & Prevention.
Supplies of IMIG nationwide shrank while manufacturers focused on producing IVIG products, which are less painful and have faster absorption rates. But IMIG remains the only product with a label indication for treating hepatitis A food poisoning. Demand for the product has not fallen in proportion to production decreases. The current shortage began after the larger of the nation's two remaining IMIG manufacturers, the state-owned Michigan Biologic Products Institute, in Lansing, interrupted production temporarily to conduct equipment maintenance. Bell downplayed recent press reports that the shortage was at a critical level. "To my knowledge, I haven't heard about any instances where people were unable to locate immune globulin."
The Council of State & Territorial Epidemiologists (CSTE), working with the CDC, recently advised state health professionals to prioritize use of IMIG for postexposure prophylaxis following exposure to hepatitis A. Facilities that have exhausted their immune globulin supplies for this use are advised to contact state health departments, which are now inventorying statewide supplies.
If IMIG is not available, the CDC's Web site suggests health-care providers, "at physician discretion," consider using tetanus immune globulin instead--but only as treatment for the highest-priority cases involving postexposure hepatitis A therapy. CDC feels the latest IMIG product shortage is temporary, with normal inventory levels to be restored within weeks.
A possible fix for the chronic IMIG shortfall may be in the works. Jimmy Hendricks, spokesman for Centeon LLC, said the FDA is reviewing the firm's NDA for Gammar-PIM, a pasteurized version of IMIG. According to an article in The Wall Street Journal, Jay Epstein, M.D., director of the FDA's Office of Blood Research & Review, said the agency will consider a fast-track approval for the product, which could significantly reduce the chance of future shortages.