Parenteral Drug Products Containing Aluminum as an Ingredient or a Contaminant: Response to Food and Drug Administration Notice of Intent and Request for Information

Abstract

Aluminum remains a significant contaminant of total parenteral nutrition (TPN) solutions and may be elevated in bone, urine, and plasma of infants receiving TPN. Aluminum accumulation in tissues of uremic patients and adult TPN patients has been associated with low-turnover bone disease. Furthermore, aluminum has also been linked with encephalopathy and anemia in uremic patients and with hepatic cholestasis in experimental animals. Because of the toxic effects of aluminum, the Food and Drug Administration (FDA) recently published a notice of intent to set an upper limit of 25 micrograms/L for aluminum in large-volume parenterals and to require manufacturers of small-volume parenterals, such as calcium and phosphate salts, to measure aluminum content and note this content on the package label. The ASCN/A.S.P.E.N. Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions supports these intentions and further urges the FDA to require that cumulative aluminum intake in terms of safe, unsafe, and toxic quantities of aluminum per kilogram be made known to physicians and pharmacists preparing the TPN solutions, to ensure that manufacturers use appropriate control procedures in aluminum measurements, and to employ a standard unit of aluminum measurement.