Document ID: FDA-2016-D-1692-0001
Agency: fda
Document Type: Notice
Title: Elemental Impurities in Drug Products; Draft Guidance for Industry;
Availability
Posted Date: 2016-07-01T04:00Z

[Federal Register Volume 81, Number 127 (Friday, July 1, 2016)]
[Notices]
[Pages 43211-43212]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-15704]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-1692]

Elemental Impurities in Drug Products; Draft Guidance for 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the availability of a draft guidance for industry entitled ``Elemental 
Impurities in Drug Products.'' This draft guidance provides 
recommendations regarding the control of elemental impurities of human 
drug products marketed in the United States consistent with 
implementation of International Council for Harmonisation (ICH) 
guidance for industry ``Q3D Elemental Impurities.'' This draft guidance 
will also assist manufacturers of compendial drug products in 
responding to the issuance of the United States Pharmacopeia (USP) 
requirement for the control of elemental impurities.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by August 30, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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.''

[[Page 43212]]

    Instructions: All submissions received must include the Docket No. 
FDA-2016-D-1692 for Elemental Impurities in Drug Products. Received 
comments will be placed in the docket and, except for those submitted 
as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    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; or 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 draft guidance document.

FOR FURTHER INFORMATION CONTACT: John Kauffman, Center for Drug 
Evaluation and Research (HFD-920), Food and Drug Administration, 645 S. 
Newstead Ave., St. Louis, MO 63110, 314-539-2168; or Stephen Ripley, 
Center for Biologics Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver 
Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Elemental Impurities in Drug Products.'' This draft guidance 
provides recommendations regarding the control of elemental impurities 
of human drug products marketed in the United States consistent with 
implementation of ICH Q3D. The draft guidance will also assist 
manufacturers of compendial drug products in responding to the issuance 
of the USP requirement for the control of elemental impurities.
    USP introduced new limits and analytical procedures for elemental 
impurities in General Chapters Elemental Impurities--Limits and 
Elemental Impurities--Procedures. Their primary goals are to (1) set 
limits for acceptable levels of elemental impurities in finished drug 
products, and (2) update the methodology used to test for elemental 
impurities in drug products to include modern analytical procedures. 
ICH Q3D contains recommendations for manufacturers of human drugs and 
biologics on applying a risk-based approach to control elemental 
impurities and permitted daily exposure. USP worked closely with ICH to 
align its new General Chapters with ICH Q3D.
    Because elemental impurities pose toxicological concerns and do not 
provide any therapeutic benefit to the patient, their levels in drug 
products should be controlled within acceptable limits. In general, FDA 
recommends that the manufacturer of any U.S. marketed drug product 
follow ICH Q3D recommendations to establish appropriate procedures for 
identifying and controlling elemental impurities in the drug product 
based on risk assessment and product-specific considerations, unless 
the drug product must comply with USP-NF requirements. This draft 
guidance outlines approaches for implementation of USP, and ICH Q3D in 
new and existing products.
    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 elemental 
impurities in drug products. 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. The Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR part 314 for submitting 
NDAs and ANDAs, including supplemental applications and annual reports, 
have been approved under OMB control number 0910-0001. The collections 
of information in 21 CFR part 211 and part 212 (CGMPs) have been 
approved under OMB control numbers 0910-0139 and 0910-0667.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.regulations.gov.

    Dated: June 27, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-15704 Filed 6-30-16; 8:45 am]
 BILLING CODE 4164-01-P