Aluminum in Large-Volume Injections (LVIs), Small-Volume Injections (SVIs), and Pharmacy Bulk
Packages (PBPs) Used in Parenteral Nutrition (PN) Therapy
2
1. The aluminum content of LVIs used in PN therapy must not exceed 25 mcg/L.
2. The package insert of LVIs used in PN therapy must state that the drug product contains no more than 25 mcg of
aluminum per liter. This information must be contained in the Precautions section of the labeling of all LVIs used in PN
therapy.
3. If the maximum amount of aluminum in SVIs and PBPs is 25 mcg/L or less, instead of stating the exact amount of
aluminum that each contains, as in paragraph (4), the immediate container label for SVIs and PBPs used in the
preparation of PN admixtures or formulations (with exceptions as noted below) may state: “Contains no more than 25
mcg/L of aluminum.” If the SVI or PBP is a lyophilized powder, the immediate container label may state the following:
“When reconstituted in accordance with the package insert instructions, the concentration of aluminum will be no
more than 25 mcg/L.”
4. The maximum level of aluminum at expiry must be stated on the immediate container label of all SVIs and PBPs used
in the preparation of PN admixtures or formulations. The aluminum content must be stated as follows: “Contains no
more than ___ mcg/L of aluminum.” The immediate container label of all SVIs and PBPs that are lyophilized powders
used in the preparation of PN solutions must contain the following statement: “When reconstituted in accordance
with the package insert instructions, the concentration of aluminum will be no more than ___ mcg/L.” This maximum
amount of aluminum must be stated as the highest one of the following three levels:
• The highest level for the batches produced during the past 3 years
• The highest level for the latest 5 batches
• The maximum level in terms of historical levels, but only until completion of production of the first 5 batches.
The package insert for all LVIs, SVIs, and PBPs used in the preparation of PN admixtures or formulations must contain the
following statement in the Warnings section of the labeling:
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged
parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their
kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral
levels of aluminum at greater than 4 to 5 mcg/kg/day, accumulate aluminum at levels associated with central nervous
system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Change to read:
LABELS AND LABELING FOR PRODUCTS IN OTHER CATEGORIES
Labels and Labeling of Liquids and Constituted Products
The labels
1
and labeling state the following information:
1.
In the case of a liquid product, the percentage content of each active moiety or drug substance or the amount of each
active moiety or drug substance in a specified volume.
2. In the case of a product to which a diluent must be added before use, the amount of each active moiety or drug
substance, the name and volume of diluent to be added, the final volume of solution, the concentration after the
diluent is added (e.g., quantity/mL or quantity/5 mL), directions for proper storage of the constituted solution, and an
expiration or BUD (see Expiration Date and Beyond-Use Date).
Amount of Active Moiety or Drug Substance per Dosage Unit
The strength of a drug product is expressed on the container label in terms of micrograms, milligrams, grams, or
percentage of the therapeutically active moiety or drug substance, whichever form is used in the title, unless otherwise
indicated in an individual monograph. Both the active moiety and drug substance names and their equivalent amounts are
then provided on the container label and in the labeling (see Nomenclature á1121ñ, Monograph Naming Policy for Salt Drug
Substances in Drug Products and Compounded Preparations).
Official articles in capsule, tablet, or other dosage forms must be labeled to express the quantity of each active moiety or
drug substance contained in each unit. Unit-dose oral solutions or suspensions (whether supplied as liquid products or as
liquid products that are constituted from solids upon addition of a designated volume of a specific diluent) must be labeled
to express the quantity of each active moiety or drug substance delivered under the conditions prescribed in Deliverable
Volume á698ñ. Official drug products not in unit-dose packaging must be labeled to show the quantity of each active moiety
or drug substance in each milliliter or in each gram, or to express the percentage of each such ingredient (see General
Notices, 8.140 Percentage Concentrations). Exceptions are oral liquids or solids intended to be constituted to yield oral liquids
that, alternatively, can be labeled in terms of each 5-mL portion of the liquid or resulting liquid. Unless otherwise required by
regulation [e.g., over-the-counter (OTC) regulation 21 CFR §201.62(b)] or indicated in a monograph or chapter, declarations
of strength or quantity must be stated only in metric units [see also General Notices, 5.50.10 Units of Potency (Biological)].
2
See 21 CFR §201.323. USP uses the following terms: large-volume injections (LVIs), small-volume injections (SVIs), and parenteral nutrition (PN),
rather than terminology used in 21 CFR §201.323: large-volume parenterals, small-volume parenterals, and total parenteral nutrition.
4 á7ñ Revision Bulletin
Official September 1, 2019
© 2019 The United States Pharmacopeial Convention All Rights Reserved.
C234255-M4908-NL2015, rev. 00 20190830