[Federal Register Volume 75, Number 138 (Tuesday, July 20, 2010)]
[Notices]
[Pages 42098-42099]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-17618]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-N-0327]
International Conference on Harmonisation; Draft 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 draft 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 draft recommendation was prepared
under the auspices of the International Conference on Harmonisation of
Technical Requirements for Registration of Pharmaceuticals for Human
Use (ICH).
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 recommendation before it begins work on the final recommendation,
submit either electronic or written comments on the document by
September 20, 2010.
ADDRESSES: Submit written requests for single copies of the draft
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, suite 200N, 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 draft 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 guidance: David Jacobson-Kram, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Silver Spring, MD 20993, 301-796-0175.
Regarding the ICH: Michelle Limoli, Office of International
Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-4480.
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
[[Page 42099]]
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 the Federal Register of December 24, 1997 (62 FR 67377), FDA
published the ICH guidance for industry entitled ``Q3C Impurities:
Residual Solvents.'' The guidance makes recommendations as to what
amounts of residual solvents are considered safe in pharmaceuticals.
The guidance recommends use of less toxic solvents and describes levels
considered to be toxicologically acceptable for some residual solvents.
Upon issuance in 1997, the text and appendix 1 of the guidance
contained several tables and a list of solvents categorizing residual
solvents by toxicity, classes 1 through 3, with class 1 being the most
toxic. The ICH Quality Expert Working Group (EWG) agreed that the PDE
could be modified if reliable and more relevant toxicity data were
brought to the attention of the group and the modified PDE could result
in a revision of the tables and list.
In 1999, ICH instituted a Q3C maintenance agreement and formed a
maintenance EWG (Q3C EWG). The agreement provided for the revisitation
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 PDE. 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. Draft Recommendation to Revise the PDE for Cumene
In March 2010, the ICH Steering Committee agreed that a draft
recommendation to revise the PDE for the solvent cumene should be made
available for public comment. The draft recommendation is the product
of the Q3C EWG of the ICH. Comments about this draft will be considered
by FDA and the Q3C EWG.
The draft recommendation addresses the safety classification of
cumene. When the Q3C guidance was published in 1997, cumene was listed
as a class 3 solvent (i.e., a solvent with low toxicity). The Q3C EWG
has 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. In March 2010, the ICH Steering
Committee was briefed on the results of the Q3C EWG's analysis. The
recommendation was to move cumene from class 3 into class 2. The
analysis and draft recommendation are available for review on the
Internet (see section IV of this document).
This draft recommendation is being issued consistent with FDA's
good guidance practices regulation (21 CFR 10.115). The draft
recommendation for the solvent cumene, when finalized, will represent
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. It is no
longer necessary to send two copies of mailed comments. Identify
comments with the docket number found in brackets in the heading of
this document. The draft 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 to Documents and the Maintenance Procedures
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/BiologicsBloodVaccines/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: July 9, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-17618 Filed 7-19-10; 8:45 am]
BILLING CODE 4160-01-S