[Federal Register Volume 71, Number 38 (Monday, February 27, 2006)]
[Notices]
[Pages 9829-9830]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-2727]


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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://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