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Notice

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

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Information about this document as published in the Federal Register.

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AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

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.

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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.

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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.Start Printed 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.

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Dated: September 4, 2015.

Leslie Kux,

Associate Commissioner for Policy.

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[FR Doc. 2015-22835 Filed 9-9-15; 8:45 am]

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