Notice2022-26564
Small Volume Parenteral Drug Products and Pharmacy Bulk Packages for Parenteral Nutrition: Aluminum Content and Labeling Recommendations; Draft Guidance for Industry; Availability
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Published
December 7, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Small Volume Parenteral Drug Products and Pharmacy Bulk Packages for Parenteral Nutrition: Aluminum Content and Labeling Recommendations." This draft guidance is intended to clarify the key factors in determining the appropriate aluminum content in a small volume parenteral (SVP) drug product and/or a pharmacy bulk package (PBP) intended as a component of parenteral nutrition (PN) and provide FDA's recommendations regarding the concentration of aluminum in SVP drug products and PBPs for PN. Additionally, this guidance is intended to assist applicants in determining the appropriate content and placement of information on aluminum in SVP and PBP human prescription drug product labeling.
Full Text
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<title>Federal Register, Volume 87 Issue 234 (Wednesday, December 7, 2022)</title>
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[Federal Register Volume 87, Number 234 (Wednesday, December 7, 2022)]
[Notices]
[Pages 75052-75054]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-26564]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-D-2301]
Small Volume Parenteral Drug Products and Pharmacy Bulk Packages
for Parenteral Nutrition: Aluminum Content and Labeling
Recommendations; Draft Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a draft guidance for industry entitled ``Small
Volume Parenteral Drug Products and Pharmacy Bulk Packages for
Parenteral Nutrition: Aluminum Content and Labeling Recommendations.''
This draft guidance is intended to clarify the key factors in
determining the appropriate aluminum content in a small volume
parenteral (SVP) drug product and/or a pharmacy bulk package (PBP)
intended as a component of parenteral nutrition (PN) and provide FDA's
recommendations regarding the concentration of aluminum in SVP drug
products and PBPs for PN. Additionally, this guidance is intended to
assist applicants in determining the appropriate content and placement
of information on aluminum in SVP and PBP human prescription drug
product labeling.
DATES: Submit either electronic or written comments on the draft
guidance by February 6, 2023 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance.
ADDRESSES: You may submit comments on any guidance at any time as
follows:
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2022-D-2301 for ``Small Volume Parenteral Drug Products and
Pharmacy Bulk Packages for Parenteral Nutrition: Aluminum Content and
Labeling Recommendations.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The
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second copy, which will have the claimed confidential information
redacted/blacked out, will be available for public viewing and posted
on <a href="https://www.regulations.gov">https://www.regulations.gov</a>. Submit both copies to the Dockets
Management Staff. If you do not wish your name and contact information
to be made publicly available, you can provide this information on the
cover sheet and not in the body of your comments and you must identify
this information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of the draft guidance to
the Division of Drug Information, Center for Drug Evaluation and
Research, Food and Drug Administration, 10001 New Hampshire Ave.,
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one
self-addressed adhesive label to assist that office in processing your
requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document.
FOR FURTHER INFORMATION CONTACT: Thao Vu, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 22, Rm. 5232, Silver Spring, MD 20993-0002, 241-308-2929.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Small Volume Parenteral Drug Products and Pharmacy Bulk
Packages for Parenteral Nutrition: Aluminum Content and Labeling
Recommendations.'' Aluminum, one of the most abundant metallic elements
on earth, occurs naturally in several minerals, ores, oxides, and
silicates. Although humans are exposed to aluminum through drinking
water, foods, and drugs, aluminum's oral bioavailability is poor, so
healthy individuals typically face little risk of toxicity. Despite
that, aluminum toxicity has been documented in medical literature for
more than 30 years, with manifestations that include osteomalacia and
reduced bone mineralization, neurological dysfunction and dialysis
encephalopathy, microcytic hypochromic anemia, and cholestasis.
A long-implicated, major source of aluminum exposure is PN,
resulting from contamination of ingredients. Patients with underlying
renal impairment who receive prolonged courses of PN support are at
greatest risk of exposure to toxic levels of aluminum from PN. Preterm
neonates and infants who often require many days of PN support and have
immature kidneys that are incapable of excreting aluminum efficiently
are at particularly high risk.
Research indicates that patients with renal impairment, including
premature neonates, who receive parenteral levels of aluminum at
greater than 4 to 5 microgram/kilogram/day (mcg/kg/day) accumulate
aluminum at levels associated with central nervous system and bone
toxicity. Because patients with renal impairment, including all preterm
neonates, comprise a major portion of those requiring PN support, we
recommend that the total aluminum exposure (TAE) from PN uniformly
should not exceed 5 mcg/kg/day. To determine TAE, one must consider all
sources of aluminum content in PN, including each large volume
parenteral and each SVP drug product and PBP in PN. This guidance
describes an approach to deriving the recommended aluminum
concentration limit in an SVP drug product for PN, based on the
proposed clinical dose, concentration of drug or dose volume, and the
known or estimated contribution of aluminum from other products in the
PN.
Additionally, this guidance is intended to assist applicants in
determining the appropriate content and placement of information on
aluminum in SVP and PBP human prescription drug product labeling. This
guidance provides recommendations to help ensure that information on
the aluminum content is appropriate and placed in the proper sections
and subsections within the Highlights of Prescribing Information and on
the container label and carton labeling. This will help to assure that
the information is clear and accessible to healthcare practitioners and
includes content that guides the safe and effective use of the drug
product.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the current thinking of FDA on ``Small Volume
Parenteral Drug Products and Pharmacy Bulk Packages for Parenteral
Nutrition: Aluminum Content and Labeling Recommendations.'' It does not
establish any rights for any person and is not binding on FDA or the
public. You can use an alternative approach if it satisfies the
requirements of the applicable statutes and regulations.
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 314 have been approved under OMB control
number 0910-0001. The collections of information in 21 CFR part 312
have been approved under OMB control number 0910-0014. The collections
of information in FDA's guidance entitled ``Formal Meetings Between the
FDA and Sponsors or Applicants of PDUFA Products'' (available at
<a href="https://www.fda.gov/media/109951/download">https://www.fda.gov/media/109951/download</a>) have been approved under OMB
control numbers 0910-0001 and 0910-0429. The collections of information
in 21 CFR 201.56 and 201.57 have been approved under OMB control number
0910-0572. The collections of information in FDA's guidance entitled
``Formal Meetings Between FDA and ANDA Applicants of Complex Products
Under GDUFA'' (available at <a href="https://www.fda.gov/media/107626/download">https://www.fda.gov/media/107626/download</a>)
have been approved under OMB control number 0910-0718. The collections
of information in FDA's guidance entitled ``Controlled Correspondence
Related to Generic Drug Development'' (available at <a href="https://www.fda.gov/media/109232/download">https://www.fda.gov/media/109232/download</a>) have been approved under OMB control
number 0910-0797.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
[[Page 75054]]
Dated: December 1, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-26564 Filed 12-6-22; 8:45 am]
BILLING CODE 4164-01-P
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