[Federal Register: February 27, 2006 (Volume 71, Number 38)]
[Notices]
[Page 9829-9830]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27fe06-65]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2006N-0080]
Agency Information Collection Activities; Proposed Collection;
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 an
opportunity for public comment on the proposed collection of certain
information by the agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension of an existing collection of
information, and to allow 60 days for public comment in response to the
notice. This notice solicits comments on 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).
DATES: Submit written or electronic comments on the collection of
information by April 28, 2006.
ADDRESSES: Submit electronic comments on the collection of information
to: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. Submit written comments on
the collection of information to the Division of Dockets Management
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: Karen Nelson, Office of Management
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-1482.
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal
agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed collection
of information set forth in this document.
With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
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 for the labeling
requirements for aluminum content in LVPs, SVPs, and PBPs used in TPN.
As explained in the final rule on aluminum content labeling
requirements published in the Federal Register of January 26, 2000 (65
FR 4103) (the January 2000, final rule), 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
[[Page 9830]]
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 are as follows:
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 (microg)/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.
Section 201.323(e) (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) consists of submitting application supplements
to FDA containing the revised labeling for each product, and analytical
method validation must be submitted under Sec. 201.323(e). During the
period since the publication of the January 2000, final rule, FDA has
received approximately 100 supplements and analytical method validation
from approximately four respondents. Because the final rule was
effective on July 26, 2004, FDA expects to receive fewer submissions
per year. FDA estimates that it will take approximately 14 hours to
prepare and submit to FDA each submission.
FDA estimates the burden of this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
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No. of Annual Frequency per Total Annual Hours per
21 CFR Section Respondents Response Responses Response Total Hours
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201.323(b),(c),(d) 4 1.25 5 14 70
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201.323(e) 4 1.25 5 14 70
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Total 140
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\1\There are no capital costs or operating and maintenance costs associated with this collection.
Dated: February 21, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-2727 Filed 2-24-06; 8:45 am]
BILLING CODE 4160-01-S