Sharing Alumninum Content

FDA is asking for feedback on its means of collecting labeling warnings.

Daphne Allen, Editor

Several years after releasing its final rule on aluminum-content labeling requirements, FDA is asking for comments on the collection of such labeling information. FDA requires labeling statements on aluminum content in parenteral drug products because the agency says that toxic accumulation of aluminum can occur in the tissues of individuals receiving total parenteral nutrition (TPN) therapy. The final rule, “Aluminum in Large and Small Volume Parenterals Used in Total Parenteral Nutrition” (21 CFR 201.323), was released in January 2000. It became effective on July 26, 2004.

Written or electronic comments on the collection of labeling requirements for aluminum content in large-volume parenterals (LVPs), small-volume parenterals (SVPs), and pharmacy bulk packages (PBPs) are requested by April 28, 2006.

FDA is posing the following questions:

• Will the proposed collection of information be necessary for the proper performance of FDA’s functions, including whether the information will have practical utility?

• Is FDA’s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used, accurate?

• How can the quality, utility, and clarity of the information to be collected be enhanced?

• How can the burden of the collection of information on respondents, including through the use of automated collection techniques, be minimized?

The agency cites research indicating that “neonates and patient populations with impaired kidney function may be at high risk of exposure to unsafe amounts of aluminum,” FDA writes. “Studies show that aluminum may accumulate in the bone, urine, and plasma of infants receiving TPN. Many drug products used routinely in parenteral therapy may contain levels of aluminum sufficiently high to cause clinical manifestations.”

When drugs and other products are taken orally, the gastrointestinal tract can usually serve as a barrier to aluminum absorption, so aluminum isn’t typically deposited in body tissues. But this barrier is circumvented when drugs containing aluminum are administered parenterally.

FDA updated its regulations to add labeling requirements for aluminum content in LVPs, SVPs, and PBPs used in TPN. It denoted an upper limit of aluminum permitted in LVPs, and it required applicants to submit to FDA-validated assay methods for determining aluminum content in parenteral drug products. Rules for information reporting include:

• Section 201.323(b) (21 CFR 201.323(b)) requires that “the package insert of all large-volume parenterals used in total parenteral nutrition therapy state that the drug product contains no more than 25 micrograms (µg)/liter (L). This information must be contained in the Precautions’ section of the labeling of all LVPs used in TPN therapy.”

• Section 201.323(c) (21 CFR 201.323(c)) requires that “the maximum level of aluminum present at expiry be stated on the immediate container label of all SVP drug products and PBPs used in the preparation of TPN solutions. The aluminum content must be stated as prescribed in the regulation. The immediate container label of all SVP drug products and PBPs that are lyophilized powders used in the preparation of TPN solutions must contain the statement prescribed in the regulation.”

• Section 201.323(d) (21 CFR 201.323(d)) requires that “the package insert for all LVPs, SVPs, and PBPs used in TPN contain a warning statement, prescribed in the regulation, intended for patients with impaired kidney function and for neonates receiving TPN therapy. This information must be contained in the Warnings’ section of the labeling.”

Manufacturers must submit application supplements to FDA containing the revised labeling for each product, and analytical method validation must be submitted under Section 201.323(e). Since the final rule’s publication, FDA has received approximately 100 supplements and analytical method validation from approximately four respondents.

For more information, contact Karen Nelson, Office of Management Programs (HFA-250), FDA, 5600

Fishers Ln., Rockville, MD 20857; 301/827-1482.

Submit electronic comments on the collection of information to:


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