Document ID: FDA-2013-D-1156-0032
Agency: fda
Document Type: Notice
Title: Q3D(R2)—Guideline for Elemental Impurities; International Council for Harmonisation; Guidance for Industry; Availability
Posted Date: 2022-09-15T04:00Z

[Federal Register Volume 87, Number 178 (Thursday, September 15, 2022)]
[Notices]
[Pages 56683-56684]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-19997]

[[Page 56683]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-D-1156]

Q3D(R2)--Guideline for Elemental Impurities; International 
Council for Harmonisation; 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 final guidance for industry entitled ``Q3D(R2) 
Guideline for Elemental Impurities.'' The guidance was prepared under 
the auspices of the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH), 
formerly the International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use. The 
guidance revises the guidance for industry ``Q3D(R1) Elemental 
Impurities'' issued in March 2020 to provide Permissible Daily 
Exposures (PDEs) for the cutaneous and transcutaneous routes of 
administration. It also provides relevant risk assessment 
considerations to supplement previous guidance for the oral, 
parenteral, and inhalation routes of administration. The guidance is 
intended to provide recommendations for acceptable amounts of the 
listed elemental impurities for pharmaceutical products and for 
conducting risk assessments.

DATES: The announcement of the guidance is published in the Federal 
Register on September 15, 2022.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances 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-2013-D-1156 for ``Q3D(R2) Guideline for Elemental Impurities.'' 
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 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 this 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 the Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), 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. The guidance may also be obtained by mail by calling 
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: 
    Regarding the guidance: Timothy McGovern, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6426, Silver Spring, MD 20993-0002, 240-
402-0477.
    Regarding the ICH: Jill Adleberg, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-5259.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Q3D(R2) Guideline for Elemental Impurities.'' The guidance 
was prepared under the auspices of ICH. ICH has the mission of 
achieving greater regulatory harmonization worldwide to ensure that 
safe, effective, high-quality medicines are developed, registered, and

[[Page 56684]]

maintained in the most resource-efficient manner. By harmonizing the 
regulatory requirements in regions around the world, ICH guidelines 
have substantially reduced duplicative clinical studies, prevented 
unnecessary animal studies, standardized the reporting of important 
safety information, standardized marketing application submissions, and 
made many other improvements in the quality of global drug development 
and manufacturing and the products available to patients.
    The six Founding Members of the ICH are FDA; the Pharmaceutical 
Research and Manufacturers of America; the European Commission; the 
European Federation of Pharmaceutical Industries Associations; the 
Japanese Ministry of Health, Labour, and Welfare; and the Japanese 
Pharmaceutical Manufacturers Association. The Standing Members of the 
ICH Association include Health Canada and Swissmedic. Additionally, the 
Membership of ICH has expanded to include other regulatory authorities 
and industry associations from around the world (https://www.ich.org/).
    ICH works by involving technical experts from both regulators and 
industry parties in detailed technical harmonization work and the 
application of a science-based approach to harmonization through a 
consensus-driven process that results in the development of ICH 
guidelines. The regulators around the world are committed to 
consistently adopting these consensus-based guidelines, realizing the 
benefits for patients and for industry.
    As a Founding Regulatory Member of ICH, FDA plays a major role in 
the development of each of the ICH guidelines, which FDA then adopts 
and issues as guidance for industry. FDA's guidance documents do not 
establish legally enforceable responsibilities. Instead, they describe 
the Agency's current thinking on a topic and should be viewed only as 
recommendations, unless specific regulatory or statutory requirements 
are cited.
    In September 2020, the ICH Assembly endorsed the draft guideline 
entitled ``Q3D(R2) Guideline for Elemental Impurities'' and agreed that 
the guideline should be made available for public comment. The draft 
guideline is the product of the Q3D(R2) Working Group of the ICH. In 
the Federal Register of May 12, 2021 (85 FR 26052), FDA published a 
notice announcing the availability of the draft guidance. The notice 
gave interested persons an opportunity to submit comments by June 11, 
2021. After consideration of the comments received and revisions to the 
guideline, a final draft of the guideline was submitted to the ICH 
Assembly and endorsed by the regulatory agencies on April 26, 2022.
    The guidance revises the guidance for industry ``Q3D(R1) Elemental 
Impurities'' issued in March 2020 to provide PDEs for the cutaneous and 
transcutaneous routes of administration. It also provides relevant risk 
assessment considerations to supplement previous guidance for the oral, 
parenteral, and inhalation routes of administration and corrects errors 
to previously identified PDEs for gold (oral, parenteral, and 
inhalation routes), silver (parenteral route), and nickel (inhalation 
route). The final guidance is intended to provide recommendations for 
acceptable amounts of the listed elemental impurities for 
pharmaceutical products and for conducting risk assessments.
    This guidance represents the current thinking of FDA on ``Q3D(R2) 
Guideline for Elemental Impurities.'' 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 relating to good laboratory practice have been approved 
under OMB control number 0910-0119. The collections of information 
pertaining to current good manufacturing practice have been approved 
under OMB control number 0910-0139. The collections of information for 
new drug applications and biologics license applications have been 
approved under OMB control numbers 0910-0001 and 0910-0338, 
respectively.

III. Electronic Access

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

    Dated: September 9, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-19997 Filed 9-14-22; 8:45 am]
BILLING CODE 4164-01-P