[Federal Register Volume 71, Number 101 (Thursday, May 25, 2006)]
[Notices]
[Pages 30143-30144]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-7984]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2006N-0080]


Agency Information Collection Activities; Submission for Office 
of Management and Budget 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 a 
proposed collection of information 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 collection of information by June 
26, 2006.

ADDRESSES: OMB is still experiencing significant delays in the regular 
mail, including first class and express mail, and messenger deliveries 
are not being accepted. To ensure that comments on the information 
collection are received, OMB recommends that written comments be faxed 
to the Office of Information and Regulatory Affairs, OMB, Attn: Fumie 
Yokota, Desk Officer for FDA, FAX: 202-395-6974.

FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Management 
Programs (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) (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

[[Page 30144]]

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 are as follows:
    Section 201.323(b) (21 CFR 201.323(b)) requires that the package 
insert of all LVPs used in TPN 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.
    In the Federal Register of February 27, 2006 (71 FR 9829), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received.
    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       Total Annual        Hours per
                    21 CFR Section                         Respondents         per Response          Responses           Response         Total Hours
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201.323(b), (c), and (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 of information.


    Dated: May 18, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-7984 Filed 5-24-06; 8:45 am]
BILLING CODE 4160-01-S