[Federal Register Volume 68, Number 51 (Monday, March 17, 2003)]
[Notices]
[Pages 12701-12702]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-6227]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 02N-0496]
Agency Information Collection Activities; Submission for OMB
Review; Comment Request; Aluminum in Large and Small Volume Parenterals
Used in Total Parenteral Nutrition
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing that the
proposed collection of information listed below has been submitted to
the Office of Management and Budget (OMB) for review and clearance
under the Paperwork Reduction Act of 1995 (the PRA).
DATES: Fax written comments on the information collection provisions by
April 16, 2003.
ADDRESSES: Fax written comments on the information collection
provisions to the Office of Information and Regulatory Affairs, OMB,
Attn: Stuart Shapiro, Desk Officer for FDA, FAX 202-395-6974, or
electronically mail comments to [email protected].
FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Information
Resources Management (HFA-250), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-1482.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
Aluminum in Large and Small Volume Parenterals Used in Total Parenteral
Nutrition--21 CFR 201.323 (OMB Control Number 0910-0439)--Extension
FDA is requesting OMB approval under the PRA (44 U.S.C. 3501--3520)
for the labeling requirements for aluminum content in large volume
parenterals (LVPs), small volume parenterals (SVPs), and pharmacy bulk
packages (PBPs) used in total parenteral nutrition (TPN). As explained
in the final rule on aluminum content labeling requirements published
in the Federal Register of January 26, 2000 (65 FR 4103), aluminum
content in parenteral drug products could result in a toxic
accumulation of aluminum in the tissues of individuals receiving TPN
therapy. Research indicates that neonates and patient populations with
impaired kidney function may be at high risk of exposure to unsafe
amounts of aluminum. 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. Generally, when
medication and nutrition are administered orally, the gastrointestinal
tract acts as an efficient barrier to the absorption of aluminum, and
relatively little ingested aluminum actually reaches body tissues.
However, parenterally administered drug products containing aluminum
bypass the protective mechanism of the gastrointestinal tract and
aluminum circulates and is deposited in human tissues.
Aluminum toxicity is difficult to identify in infants because few
reliable techniques are available to evaluate bone metabolism in
premature infants. Techniques used to evaluate the effects of aluminum
on bone in adults cannot be used in premature infants. Although
aluminum toxicity is not commonly detected clinically, it can be
serious in selected patient populations, such as neonates, and may be
more common than is recognized.
FDA amended its regulations to add labeling requirements for
aluminum content in LVPs, SVPs, and PBPs used in TPN. FDA specified an
upper limit of aluminum permitted in LVPs and required applicants to
submit to FDA validated assay methods for determining aluminum content
in parenteral drug products. The agency added these requirements
because of evidence linking the use of parenteral drug products
containing aluminum to morbidity and mortality among patients on TPN
therapy, especially among premature neonates and patients with impaired
kidney function.
The information collection reporting requirements resulting from
this rulemaking are as follows:
21 CFR 201.323(b)--Requires that the package insert of all LVPs
used in TPN therapy state that the drug product
[[Page 12702]]
contains no more than 25 micrograms per liter ([mu]g/L). This
information must be contained in the ``Precautions'' section of the
labeling of all LVPs used in TPN therapy.
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.
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.
21 CFR 201.323(e)--Requires that applicants and manufacturers must
use validated assay methods to determine the aluminum content in
parenteral drug products. The assay methods must comply with current
good manufacturing practice requirements. Applicants must submit to FDA
both validation of the method used and release data for several
batches. Manufacturers of parenteral drug products not subject to an
approved application must make assay methodology available to FDA
during inspections. Holders of pending applications must submit an
amendment to the application.
Compliance with the information collection burdens under
Sec. 201.323(b), (c), and (d) (21 CFR 201.323(b), (c), and (d))
consists of submitting application supplements to FDA containing the
revised labeling for each product. Based on data concerning the number
of applications for LVPs, SVPs, and PBPs used in TPN received by the
agency, FDA estimates that the labeling for approximately 200 products
will be changed under Sec. 201.323(b), (c), and (d). FDA estimates that
it will take approximately 14 hours to prepare and submit to FDA each
labeling change. FDA estimates that approximately 65 respondents will
each submit 1 validated assay method annually under Sec. 201.323(e).
FDA estimates that it will take approximately 14 hours to prepare and
submit to FDA each validated assay.
In the Federal Register of December 19, 2002 (67 FR 77792), the
agency requested comments on the proposed collection of information. No
comments were received.
The burdens can be charted as follows:
Table 1.--Estimated Annual Reporting Burden\1\
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Annual Frequency per
21 CFR Section No. of Respondents Response Total Annual Responses Hours per Response Total Hours
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201.323(b),(c),(d) 200 1 200 14 2,800
201.323(e) 65 1 65 14 910
Total .................... .................... ...................... .................. 3,710
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: March 10, 2003.
William K. Hubbard,
Associate Commissioner for Policy and Planning.
[FR Doc. 03-6227 Filed 3-14-03; 8:45 am]
BILLING CODE 4160-01-S