80 FR 62537 - 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

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 200 (October 16, 2015)

Page Range		62537-62538
FR Document		2015-26361

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.

Federal Register, Volume 80 Issue 200 (Friday, October 16, 2015)

[Federal Register Volume 80, Number 200 (Friday, October 16, 2015)]
[Notices]
[Pages 62537-62538]
From the Federal Register Online [www.thefederalregister.org]
[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]
BILLING CODE 4164-01-P

62538 Federal Register / Vol. 80, No. 200 / Friday, October 16, 2015 / Notices

Drug Administration, 10903 New reliable and more relevant toxicity data BiologicsBloodVaccines/
Hampshire Ave., Bldg. 71, Rm. 7212, were brought to the attention of the GuidanceCompliance
Silver Spring, MD 20993–0002, 301– group and the modified PDE could RegulatoryInformation/Guidances/
796–8377. result in a revision of the tables and list. default.htm.
SUPPLEMENTARY INFORMATION: In 1999, ICH instituted a Q3C Dated: October 9, 2015.
maintenance agreement and formed a
I. Background Leslie Kux,
maintenance EWG (Q3C EWG). The
In recent years, many important agreement provided for the revisitation Associate Commissioner for Policy.
initiatives have been undertaken by of solvent PDEs and allowed for minor [FR Doc. 2015–26361 Filed 10–15–15; 8:45 am]
regulatory authorities and industry changes to the tables and list that BILLING CODE 4164–01–P
associations to promote international include the existing PDEs. The
harmonization of regulatory agreement also provided that new
requirements. FDA has participated in solvents and PDEs could be added to the DEPARTMENT OF HEALTH AND
many meetings designed to enhance tables and list based on adequate HUMAN SERVICES
harmonization and is committed to toxicity data. In the Federal Register of
February 12, 2002 (67 FR 6542), FDA Food and Drug Administration
seeking scientifically based harmonized
technical procedures for pharmaceutical briefly described the process for
development. One of the goals of proposing future revisions to the PDE. [Docket No. FDA–2015–N–3403]
harmonization is to identify and then In the same notice, the Agency
Clarifying Current Roles and
reduce differences in technical announced its decision to delink the
Responsibilities Described in the
requirements for drug development tables and list from the Q3C guidance
and create a stand-alone document Coordinated Framework for the
among regulatory agencies.
ICH was organized to provide an entitled ‘‘Q3C: Tables and List’’ to Regulation of Biotechnology and
opportunity for tripartite harmonization facilitate making changes recommended Developing a Long-Term Strategy for
initiatives to be developed with input by ICH. the Regulation of the Products of
from both regulatory and industry In June 2015, the ICH Steering Biotechnology; Public Meeting
representatives. FDA also seeks input Committee agreed that draft AGENCY: Food and Drug Administration,
from consumer representatives and recommendations for a new PDE for the HHS.
others. ICH is concerned with residual solvent triethylamine and a
ACTION: Notice of public meeting.
harmonization of technical revised PDE for the residual solvent
requirements for the registration of methylisobutylketone should be made SUMMARY: Under the auspices of the
pharmaceutical products among three available for public comment. The draft National Science and Technology
regions: Europe, Japan, and North recommendations are the product of the Council, the Food and Drug
America. The eight ICH sponsors are the Quality Expert Working Group of the Administration (FDA or the Agency),
European Commission; the European ICH. Comments about this draft will be along with the Office of Science and
Federation of Pharmaceutical Industries considered by FDA and the Quality Technology Policy (OSTP), the
Associations; the Japanese Ministry of Expert Working Group. Environmental Protection Agency
Health, Labour, and Welfare; the The draft recommendations provide (EPA), and the United States
Japanese Pharmaceutical Manufacturers guidance on the new PDE for the solvent Department of Agriculture (USDA), is
Association; CDER and CBER, FDA; the trimethylamine and the revised PDE for announcing a public meeting, to be held
Pharmaceutical Research and the solvent methylisobutylketone. In on October 30, 2015, to discuss the
Manufacturers of America; Health addition, the data used to derive the memorandum entitled, ‘‘Modernizing
Canada; and Swissmedic. The ICH PDEs are summarized. The document is the Regulatory System for
Secretariat, which coordinates the intended to recommend acceptable Biotechnology Products,’’ issued by the
preparation of documentation, is amounts for the listed residual solvents Executive Office of the President (EOP)
provided by the International in pharmaceuticals for the safety of the in July 2015. The purpose of the
Federation of Pharmaceutical patient. meeting is to inform the public about
Manufacturers Associations (IFPMA). The draft recommendations are being the activities described in the July 2015
The ICH Steering Committee includes issued consistent with FDA’s good memorandum; invite oral comments
representatives from each of the ICH guidance practices regulation (21 CFR from interested parties; and provide
sponsors and the IFPMA, as well as 10.115). The draft recommendations for information about how to submit
observers from the World Health the solvents trimethylamine and written comments, data, or other
Organization. methylisobutylketone, when finalized,
In the Federal Register of December information to the docket.
will represent the current thinking of
24, 1997 (62 FR 67377), FDA published DATES: See section II, ‘‘How to
FDA on this topic. They do not establish
the ICH guidance for industry entitled any rights for any person and are not Participate in the Public Meeting’’ in the
‘‘Q3C Impurities: Residual Solvents.’’ SUPPLEMENTARY INFORMATION section of
binding on FDA or the public. You can
The guidance makes recommendations use an alternative approach if it satisfies this document for the date and time of
as to what amounts of residual solvents the requirements of the applicable the public meeting, closing dates for
are considered to be toxicologically statutes and regulations. advance registration, and information
acceptable for some residual solvents. on deadlines for submitting either
Upon issuance in 1997, the text and II. Electronic Access electronic or written comments to FDA’s
srobinson on DSK5SPTVN1PROD with NOTICES

appendix 1 of the guidance contained Persons with access to the Internet Division of Dockets Management.
several tables and a list of solvents may obtain the document at http:// Comments may be submitted in writing
categorizing residual solvents by www.regulations.gov, http:// until November 13, 2015.
toxicity, classes 1 through 3, with class www.fda.gov/Drugs/ ADDRESSES: See section II, ‘‘How to
1 being the most toxic. The ICH Quality GuidanceCompliance Participate in the Public Meeting’’ in the
Expert Working Group (EWG) agreed RegulatoryInformation/Guidances/ SUPPLEMENTARY INFORMATION section of
that the PDE could be modified if default.htm, or http://www.fda.gov/ this document.

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Document Created: 2015-12-14 15:23:51
Document Modified: 2015-12-14 15:23:51

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
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.
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.
FR Citation		80 FR 62537

80 FR 62537 - 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

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 200 (October 16, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration