[Federal Register Volume 80, Number 200 (Friday, October 16, 2015)]
[Notices]
[Pages 62537-62538]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-26361]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2015-D-3474]
Draft Recommendations for the Permitted Daily Exposures for Two
Solvents, Triethylamine and Methylisobutylketone, According to the
Maintenance Procedures for the Guidance Q3C Impurities: Residual
Solvents; International Conference on Harmonisation; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of draft recommendations for a new permitted daily
exposure (PDE) for the residual solvent triethylamine and a revised PDE
for the residual solvent methylisobutylketone, according to the
maintenance procedures for the guidance for industry entitled ``Q3C
Impurities: Residual Solvents.'' The draft recommendations were
prepared under the auspices of the International Conference on
Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH). The document is intended to
recommend acceptable amounts for the listed residual solvents in
pharmaceuticals for the safety of the patient.
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 the
draft recommendations before it begins work on the final
recommendations, submit either electronic or written comments on the
document by December 15, 2015.
ADDRESSES: You may submit comments as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2015-D-3474 for ``Draft Recommendations for the Permitted Daily
Exposures for Two Solvents, Triethylamine and Methylisobutylketone,
According to the Maintenance Procedures for the Guidance Q3C
Impurities: Residual Solvents; International Conference on
Harmonisation; Availability.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at http://www.regulations.gov or at the Division of
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be made publicly available,
you can provide this information on the cover sheet and not in the body
of your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
Submit written requests for single copies of the draft
recommendations to the Division of Drug Information (HFD-240), Center
for Drug Evaluation and Research (CDER), Food and Drug Administration,
10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver
Spring, MD 20993-0002, 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 draft
recommendations may also be obtained by mail by calling CBER at 1-800-
835-4709 or 240-402-8010. See the SUPPLEMENTARY INFORMATION section for
electronic access to the draft recommendations.
FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Timothy J.
McGovern, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6300, Silver
Spring, MD 20993-0002, 240-402-0477.
Regarding the ICH: Michelle Limoli, CBER International Programs,
Food and
[[Page 62538]]
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: Europe, Japan, and North
America. The eight 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; CDER and CBER, FDA; the
Pharmaceutical Research and Manufacturers of America; Health Canada;
and Swissmedic. 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.
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 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.
In June 2015, the ICH Steering Committee agreed that draft
recommendations for a new PDE for the residual solvent triethylamine
and a revised PDE for the residual solvent methylisobutylketone should
be made available for public comment. The draft recommendations are the
product of the Quality Expert Working Group of the ICH. Comments about
this draft will be considered by FDA and the Quality Expert Working
Group.
The draft recommendations provide guidance on the new PDE for the
solvent trimethylamine and the revised PDE for the solvent
methylisobutylketone. In addition, the data used to derive the PDEs are
summarized. The document is intended to recommend acceptable amounts
for the listed residual solvents in pharmaceuticals for the safety of
the patient.
The draft recommendations are being issued consistent with FDA's
good guidance practices regulation (21 CFR 10.115). The draft
recommendations for the solvents trimethylamine and
methylisobutylketone, when finalized, will represent the current
thinking of FDA on this topic. They do not establish any rights for any
person and are 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. 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: October 9, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-26361 Filed 10-15-15; 8:45 am]
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