[Federal Register Volume 77, Number 36 (Thursday, February 23, 2012)]
[Notices]
[Pages 10754-10755]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-4164]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-N-0327]
International Conference on Harmonisation; Final Recommendation
for the Revision of the Permitted Daily Exposure for the Solvent Cumene
According to the Maintenance Procedures for the Guidance Q3C
Impurities: Residual Solvents; 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 final recommendation for the revision of the
permitted daily exposure (PDE) for the solvent cumene according to the
maintenance procedures for the guidance for industry entitled ``Q3C
Impurities: Residual Solvents.'' The recommendation was prepared under
the auspices of the International Conference on Harmonisation of
Technical Requirements for Registration of Pharmaceuticals for Human
Use (ICH).
DATES: Submit either electronic or written comments on Agency guidances
at any time.
ADDRESSES: Submit written requests for single copies of the
recommendation to the Division of Drug Information (HFD-240), Center
for Drug Evaluation and Research, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002,
or the Office of Communication, Outreach and Development (HFM-40),
Center for Biologics Evaluation and Research (CBER), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448. Send one
self-addressed adhesive label to assist the office in processing your
requests. The draft recommendation may also be obtained by mail by
calling CBER at 1-800-835-4709 or 301-827-1800. See the SUPPLEMENTARY
INFORMATION section for electronic access to the draft recommendation.
Submit electronic comments on the recommendation 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 Q3C Guidance
David Jacobson-Kram, Center for Drug Evaluation and Research, Food
and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 6488,
Silver Spring, MD 20993, 301-796-0175.
Regarding the ICH
Michelle Limoli, Office of International Programs, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 32, rm. 3506, Silver
Spring, MD 20993-0002, 301-796-4600.
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.
In 1999, ICH instituted a Q3C maintenance agreement and formed a
maintenance Expert Working Group (Q3C EWG). The agreement provided for
the reconsideration of solvent PDEs and allowed for minor changes to
the tables and list that include the existing PDEs. The agreement also
provided that new solvents and PDEs could be added to the tables and
list based on adequate toxicity data. In the Federal Register of
February 12, 2002 (67 FR 6542), FDA briefly described the process for
proposing future revisions to the PDEs. In the same notice, the Agency
announced its decision to delink the tables and list from the Q3C
guidance and create a stand alone document entitled ``Q3C--Tables and
List'' to facilitate making changes recommended by ICH.
II. Revised PDE for Cumene
In the Federal Register of July 20, 2010 (75 FR 42098), FDA
published a notice announcing the availability of a draft
recommendation for the revision of the PDE for cumene according to the
ICH maintenance procedures. The notice gave interested persons an
opportunity to submit comments by September 20, 2010.
After consideration of the comments received and revisions to the
guidance, a final draft of the recommendation was submitted to the ICH
Steering Committee and endorsed by the three participating regulatory
Agencies in February 2011.
The final recommendation addresses the safety classification of
cumene. When the Q3C guidance was published in 1997 (62 FR 67377,
December 24, 1997), cumene was listed as a class 3
[[Page 10755]]
solvent (i.e., a solvent with low toxicity). The Q3C EWG reviewed new
toxicity data derived from a carcinogenicity study performed by the
National Toxicology Program. The new data suggest a positive systemic
carcinogenic effect, and this observation raises the toxicity
associated with this solvent. The final recommendation is that cumene
be placed into class 2. A PDE of 0.7 milligrams per day and a
concentration limit of 70 parts per million are being declared for this
solvent. The analysis and recommendation are available for review on
the Internet (see section V of this document on electronic access). The
final recommendation is also available from the Division of Drug
Information (see ADDRESSES). The Agency will revise the tables in the
guidance ``Q3C--Tables and List'' to reflect the ICH final
recommendation for cumene.
The final recommendation for the solvent cumene is being issued
consistent with FDA's good guidance practices regulation (21 CFR
10.115). The revised PDE for the solvent cumene contained in the
revised guidance ``Q3C--Tables and List'' represents the Agency's
current thinking on this topic. It does not create or confer any rights
for or on any person and does not operate to bind FDA or the public. An
alternative approach may be used if such approach satisfies the
requirements of the applicable statutes and regulations.
III. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. 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. The recommendation and received comments may be seen in
the Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
IV. Electronic Access
Persons with access to the Internet may obtain the Q3C guidance
documents at http://www.regulations.gov, http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
http://www.fda.gov/;BiologicsBlood;Vaccines/
GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
Information on the Q3C maintenance process as well as proposals,
data analysis, and draft and final recommendations for revisions to the
tables and list are available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm125820.htm.
Dated: February 16, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-4164 Filed 2-22-12; 8:45 am]
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