Small Volume Parenteral Drug Products and Pharmacy Bulk Packages for Parenteral Nutrition: Aluminum Content and Labeling Recommendations; Draft Guidance for Industry; Availability, 75052-75054 [2022-26564]

Download as PDF 75052 Federal Register / Vol. 87, No. 234 / Wednesday, December 7, 2022 / Notices Mary B. Jones, ACF/OPRE Certifying Officer. For further information about IMJUDO (tremelimumab), approved October 23, 2022, go to the ‘‘Drugs@FDA’’ website at https://www.accessdata.fda.gov/scripts/ cder/daf/. [FR Doc. 2022–26542 Filed 12–6–22; 8:45 am] BILLING CODE 4184–82–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Dated: December 1, 2022. Lauren K. Roth, Associate Commissioner for Policy. Food and Drug Administration [FR Doc. 2022–26565 Filed 12–6–22; 8:45 am] BILLING CODE 4164–01–P [Docket No. FDA–2018–N–1262] Notice of Approval of Product Under Voucher: Rare Pediatric Disease Priority Review Voucher AGENCY: DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration, HHS. ACTION: [Docket No. FDA–2022–D–2301] Notice. The Food and Drug Administration (FDA) is announcing the issuance of approval of a product redeeming a priority review voucher. The Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA), authorizes FDA to award priority review vouchers to sponsors of approved rare pediatric disease product applications that meet certain criteria. FDA is required to publish notice of the issuance of priority review vouchers as well as the approval of products redeeming a priority review voucher. FDA has determined that IMJUDO (tremelimumab), approved October 23, 2022, meets the criteria for redeeming a priority review voucher. FOR FURTHER INFORMATION CONTACT: Cathryn Lee, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993–0002, 301–796–1394, email: Cathryn.Lee@fda.hhs.gov. SUMMARY: FDA is announcing the approval of a product redeeming a rare pediatric disease priority review voucher. Under section 529 of the FD&C Act (21 U.S.C. 360ff), which was added by FDASIA, FDA will report the issuance of rare pediatric disease priority review vouchers and the approval of products for which a voucher was redeemed. FDA has determined that IMJUDO (tremelimumab), approved October 23, 2022, meets the redemption criteria. For further information about the Rare Pediatric Disease Priority Review Voucher Program and for a link to the full text of section 529 of the FD&C Act, go to https://www.fda.gov/ForIndustry/ DevelopingProductsforRareDiseases Conditions/RarePediatricDisease PriorityVoucherProgram/default.htm. SUPPLEMENTARY INFORMATION: ddrumheller on DSK6VXHR33PROD with NOTICES Food and Drug Administration VerDate Sep<11>2014 19:54 Dec 06, 2022 Jkt 259001 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. 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: SUMMARY: Electronic Submissions Submit electronic comments in the following way: • Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. PO 00000 Frm 00031 Fmt 4703 Sfmt 4703 Comments submitted electronically, including attachments, to https:// www.regulations.gov 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 https://www.regulations.gov. • 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: • 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. • 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 https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240–402–7500. • 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 E:\FR\FM\07DEN1.SGM 07DEN1 Federal Register / Vol. 87, No. 234 / Wednesday, December 7, 2022 / Notices second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. 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: https:// www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https:// www.regulations.gov 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: ddrumheller on DSK6VXHR33PROD with NOTICES 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 VerDate Sep<11>2014 19:54 Dec 06, 2022 Jkt 259001 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. PO 00000 Frm 00032 Fmt 4703 Sfmt 4703 75053 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 https:// www.fda.gov/media/109951/download) 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 https:// www.fda.gov/media/107626/download) 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 https://www.fda.gov/media/109232/ download) have been approved under OMB control number 0910–0797. III. Electronic Access Persons with access to the internet may obtain the draft guidance at https:// www.fda.gov/drugs/guidancecompliance-regulatory-information/ guidances-drugs, https://www.fda.gov/ regulatory-information/search-fdaguidance-documents, or https:// www.regulations.gov. E:\FR\FM\07DEN1.SGM 07DEN1 75054 Federal Register / Vol. 87, No. 234 / Wednesday, December 7, 2022 / Notices Dated: December 1, 2022. Lauren K. Roth, Associate Commissioner for Policy. public, submit the comment as a written/paper submission and in the manner detailed (see ‘‘Written/Paper Submissions’’ and ‘‘Instructions’’). [FR Doc. 2022–26564 Filed 12–6–22; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2017–D–6580] Homeopathic Drug Products; Guidance for Food and Drug Administration Staff and Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a final guidance for FDA staff and industry entitled ‘‘Homeopathic Drug Products.’’ The guidance describes how FDA intends to prioritize enforcement and regulatory action with regard to drug products, including biological products, labeled as homeopathic and marketed in the United States without the required FDA approval. DATES: The announcement of the guidance is published in the Federal Register on December 7, 2022. ADDRESSES: You may submit either electronic or written comments on Agency guidances at any time as follows: ddrumheller on DSK6VXHR33PROD with NOTICES SUMMARY: Electronic Submissions Submit electronic comments in the following way: • Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https:// www.regulations.gov 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 https://www.regulations.gov. • If you want to submit a comment with confidential information that you do not wish to be made available to the VerDate Sep<11>2014 19:54 Dec 06, 2022 Jkt 259001 Written/Paper Submissions Submit written/paper submissions as follows: • 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. • 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– 2017–D–6580 for ‘‘Homeopathic Drug Products; Guidance for Food and Drug Administration Staff and Industry; Availability.’’ Received comments will be placed in the docket and, except for those submitted as ‘‘Confidential Submissions,’’ publicly viewable at https://regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240–402– 7500. • 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 second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. 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: https:// www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf. PO 00000 Frm 00033 Fmt 4703 Sfmt 4703 Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https:// www.regulations.gov 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 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; or to the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, 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 guidance document. FOR FURTHER INFORMATION CONTACT: Elaine Lippmann, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6238, Silver Spring, MD 20993, 301–796– 3602, Elaine.Lippmann@fda.hhs.gov; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993, 240–402– 7911, Stephen.Ripley@fda.hhs.gov. SUPPLEMENTARY INFORMATION: I. Background In the Federal Register on October 25, 2019 (84 FR 57441), FDA announced the availability of a revised draft guidance for FDA staff and industry entitled ‘‘Drug Products Labeled as Homeopathic.’’ This revised draft guidance was intended to describe how FDA intends to prioritize enforcement and regulatory action with regard to drug products, including biological products, labeled as homeopathic and marketed in the United States without the required FDA approval. After review of the comments received on the revised draft guidance, as well as comments on the original draft guidance published on December 20, 2017, we are issuing this final guidance with minor revisions for clarity and transparency. E:\FR\FM\07DEN1.SGM 07DEN1

Agencies

[Federal Register Volume 87, Number 234 (Wednesday, December 7, 2022)]
[Notices]
[Pages 75052-75054]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-26564]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
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 https://www.regulations.gov.
     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:
     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.
     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 https://www.regulations.gov or at the Dockets 
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
     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

[[Page 75053]]

second copy, which will have the claimed confidential information 
redacted/blacked out, will be available for public viewing and posted 
on https://www.regulations.gov. 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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov 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 
https://www.fda.gov/media/109951/download) 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 https://www.fda.gov/media/107626/download) 
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 https://www.fda.gov/media/109232/download) have been approved under OMB control 
number 0910-0797.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.


[[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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