[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