80 FR 54566 - International Conference on Harmonisation; Guidance on Q3D Elemental Impurities; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 175 (September 10, 2015)

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled ``Q3D Elemental Impurities.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance establishes permitted daily exposures for 24 elements in drug products based on evaluation of toxicity data. Permitted daily exposures are provided for each element by three routes of administration--oral, parenteral and inhalation. The guidance also provides for a risk-based approach to assessing the likelihood that elemental impurities with established permitted daily exposures will be present in a pharmaceutical product. The guidance is intended to provide a harmonized approach to control of elemental impurities in pharmaceutical products in order to avoid the uncertainty and duplication of work that results from different requirements in different ICH regions.

[Federal Register Volume 80, Number 175 (Thursday, September 10, 2015)]
[Notices]
[Pages 54566-54567]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-22835]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


International Conference on Harmonisation; Guidance on Q3D 
Elemental Impurities; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance entitled ``Q3D Elemental Impurities.'' The 
guidance was prepared under the auspices of the International 
Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use (ICH). The guidance establishes 
permitted daily exposures for 24 elements in drug products based on 
evaluation of toxicity data. Permitted daily exposures are provided for 
each element by three routes of administration--oral, parenteral and 
inhalation. The guidance also provides for a risk-based approach to 
assessing the likelihood that elemental impurities with established 
permitted daily exposures will be present in a pharmaceutical product. 
The guidance is intended to provide a harmonized approach to control of 
elemental impurities in pharmaceutical products in order to avoid the 
uncertainty and duplication of work that results from different 
requirements in different ICH regions.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of the guidance to 
the Division of Drug Information (HFD-240), Center for Drug Evaluation 
and Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993, 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 the office in processing 
your requests. The guidance may also be obtained by mail by calling 
CBER at 1-800-835-4709 or 240-402-7800. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.
    Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: John Kauffman, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
645 S. Newstead Ave., St. Louis, MO 63110, 314-539-2168;
    Regarding the ICH: Michelle Limoli, CBER International Programs, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
7212, Silver Spring, MD 20993-0002, 301-796-8377.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for tripartite 
harmonization initiatives to be developed with input from both 
regulatory and industry representatives. FDA also seeks input from 
consumer representatives and others. ICH is concerned with 
harmonization of technical requirements for the registration of 
pharmaceutical products among three regions: The European Union, Japan, 
and the United States. The six ICH sponsors are the European 
Commission; the European Federation of Pharmaceutical Industries 
Associations; the Japanese Ministry of Health, Labour, and Welfare; the 
Japanese Pharmaceutical Manufacturers Association; the Centers for Drug 
Evaluation and Research and Biologics Evaluation and Research, FDA; and 
the Pharmaceutical Research and Manufacturers of America. The ICH 
Secretariat, which coordinates the preparation of documentation, is 
provided by the International Federation of Pharmaceutical 
Manufacturers Associations (IFPMA).
    The ICH Steering Committee includes representatives from each of 
the ICH sponsors and the IFPMA, as well as observers from the World 
Health Organization, Health Canada, and the European Free Trade Area.

[[Page 54567]]

    In the Federal Register of October 23, 2013 (78 FR 63219), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``Q3D Elemental Impurities.'' The notice gave interested 
persons an opportunity to submit comments by December 23, 2013.
    After consideration of the comments received and revisions to the 
guidance, a final draft of the guidance was submitted to the ICH 
Steering Committee and endorsed by the three participating regulatory 
agencies on December 16, 2014.
    The guidance establishes permitted daily exposures for 24 elements 
in drug products and provides for a risk-based approach to assessing 
the likelihood that elemental impurities with established permitted 
daily exposures will be present in a pharmaceutical product. In 
response to comments on the draft guidance, several changes were made 
to the final guidance including clarifying the scope, reevaluation of 
some permitted daily exposures based on new toxicology data, 
simplification of the classification scheme for elemental impurities, 
and clarifying the examples to illustrate certain concepts within the 
guidance.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on Q3D elemental impurities. It does 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. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

III. Electronic Access

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

    Dated: September 4, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-22835 Filed 9-9-15; 8:45 am]
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