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 Council for Harmonisation; Guidance for Industry; Availability, 34537-34538 [2017-15537]
Download as PDF
Federal Register / Vol. 82, No. 141 / Tuesday, July 25, 2017 / Notices
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2015–D–3474]
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 Council for
Harmonisation; Guidance for Industry;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of
recommendations for a new permitted
daily exposure (PDE) for the residual
solvent triethylamine and a revised PDE
for the residual solvent
methylisobutylketone. The PDEs were
developed according to the methods for
establishing exposure limits included in
the guidance for industry entitled ‘‘Q3C
Impurities: Residual Solvents.’’ The
recommendations were prepared under
the auspices of the International Council
for Harmonisation (ICH), formerly the
International Conference on
Harmonisation. The document is
intended to recommend acceptable
amounts for the listed residual solvents
in pharmaceuticals for the safety of the
patient.
DATES: Submit either electronic or
written comments on Agency guidances
at any time.
ADDRESSES: You may submit comments
as follows:
mstockstill on DSK30JT082PROD with NOTICES
SUMMARY:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
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
VerDate Sep<11>2014
19:30 Jul 24, 2017
Jkt 241001
comments, that information will be
posted on https://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): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, 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 ‘‘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 Council for
Harmonisation; Guidance for Industry;
Availability.’’ Received comments will
be placed in the docket and, except for
those submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Dockets Management Staff 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
https://www.regulations.gov. Submit
both copies to the Dockets Management
Staff. 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
PO 00000
Frm 00066
Fmt 4703
Sfmt 4703
34537
‘‘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: https://www.gpo.gov/
fdsys/pkg/FR-2015-09-18/pdf/201523389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
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 Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852.
Submit written requests for single
copies of this guidance to the Division
of Drug Information, 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 that office in processing
your requests. The guidance may also be
obtained by mail by calling CBER at
800–835–4709 or 240–402–8010. See
the SUPPLEMENTARY INFORMATION section
for electronic access to the guidance
document.
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: Amanda Roache,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 1176, Silver Spring,
MD 20993–0002, 301–796–4548.
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
E:\FR\FM\25JYN1.SGM
25JYN1
mstockstill on DSK30JT082PROD with NOTICES
34538
Federal Register / Vol. 82, No. 141 / Tuesday, July 25, 2017 / Notices
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 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 for human use
among regulators around the world. The
six founding members of the ICH 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; and the Pharmaceutical
Research and Manufacturers of America.
The Standing Members of the ICH
Association include Health Canada and
Swissmedic. Any party eligible as a
Member in accordance with the ICH
Articles of Association can apply for
membership in writing to the ICH
Secretariat. The ICH Secretariat, which
coordinates the preparation of
documentation, operates as an
international nonprofit organization and
is funded by the Members of the ICH
Association. The ICH Assembly is the
overarching body of the Association and
includes representatives from each of
the ICH members and observers.
In the Federal Register of December
24, 1997 (62 FR 67377), FDA published
a notice announcing the availability of
the ICH guidance for industry entitled
‘‘Q3C Impurities: Residual Solvents.’’
The guidance makes recommendations
as to what amounts of residual solvents
are considered 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 for new
VerDate Sep<11>2014
19:30 Jul 24, 2017
Jkt 241001
solvents and PDEs that 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, available at https://
www.fda.gov/downloads/drugs/
guidancecomplianceregulatory
information/guidances/ucm073395.pdf.
The ‘‘Q3C: Tables and List’’ has been
updated as of January 2017 to include
the recommended PDE for triethylamine
and methylisobutylketone.
In the Federal Register of October 16,
2015 (80 FR 62537), FDA published a
notice announcing the availability of
draft recommendations for the PDEs for
two solvents, trimethylamine and
methylisobutylketone, according to the
maintenance procedures for the
guidance entitled ‘‘Q3C Impurities:
Residual Solvents,’’ available at https://
www.fda.gov/ucm/groups/fdagovpublic/@fdagov-drugs-gen/documents/
document/ucm073394.pdf. The notice
gave interested persons an opportunity
to submit comments by December 15,
2015. After consideration of the
comments received and revisions to the
guidance, a final draft of the
recommendations was submitted to the
ICH Assembly and endorsed by the
regulatory agencies in November 2016.
The guidance provides a new PDE for
the solvent trimethylamine and a
revised PDE for the solvent
methylisobutylketone. In addition, the
data used to derive the PDEs are
summarized. Revisions made to the
final guidance as a result of comments
include a modification of the PDE for
methylisobutylketone from 22.6
milligrams (mg)/day to 45 mg/day based
on reconsideration of the severity of
effects identified in rat studies and the
human relevance of effects identified in
mouse carcinogenicity study. The
recommendation to place
methylisobutylketone into class 2
remains. The ‘‘Q3C: Tables and List’’
has been updated as of January 2017 to
include the recommended PDE for
triethylamine and
methylisobutylketone.
This guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The guidance represents the current
thinking of FDA on ‘‘Q3C Impurities:
Residual Solvents.’’ It does not establish
any rights for any person and is not
binding on FDA or the public. You can
PO 00000
Frm 00067
Fmt 4703
Sfmt 4703
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 https://
www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm, https://
www.fda.gov/BiologicsBloodVaccines/
GuidanceCompliance
RegulatoryInformation/Guidances/
default.htm, or https://
www.regulations.gov.
Dated: July 18, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning,
Legislation, and Analysis.
[FR Doc. 2017–15537 Filed 7–24–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2015–D–3235]
M4E(R2): The Common Technical
Document—Efficacy; International
Council for Harmonisation; Guidance
for Industry; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a
guidance entitled ‘‘M4E(R2): The CTD—
Efficacy.’’ The guidance was prepared
under the auspices of the International
Council for Harmonisation (ICH),
formerly the International Conference
on Harmonisation. The guidance revises
the ICH guidance ‘‘M4E: The CTD—
Efficacy’’ (M4E guidance). The revised
guidance standardizes the presentation
of benefit-risk information in regulatory
submissions, providing greater
specificity on the format and structure
of benefit-risk information. This
revision is intended to facilitate
communication among regulators and
industry.
SUMMARY:
Submit either electronic or
written comments on Agency guidance’s
at any time.
ADDRESSES: You may submit comments
as follows:
DATES:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
E:\FR\FM\25JYN1.SGM
25JYN1
Agencies
[Federal Register Volume 82, Number 141 (Tuesday, July 25, 2017)]
[Notices]
[Pages 34537-34538]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-15537]
[[Page 34537]]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2015-D-3474]
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 Council for Harmonisation; Guidance for
Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of recommendations for a new permitted daily exposure
(PDE) for the residual solvent triethylamine and a revised PDE for the
residual solvent methylisobutylketone. The PDEs were developed
according to the methods for establishing exposure limits included in
the guidance for industry entitled ``Q3C Impurities: Residual
Solvents.'' The recommendations were prepared under the auspices of the
International Council for Harmonisation (ICH), formerly the
International Conference on Harmonisation. The document is intended to
recommend acceptable amounts for the listed residual solvents in
pharmaceuticals for the safety of the patient.
DATES: Submit either electronic or written comments on Agency guidances
at any time.
ADDRESSES: You may submit comments as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, 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 ``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 Council for Harmonisation; Guidance for
Industry; Availability.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at https://www.regulations.gov or at the Dockets
Management Staff 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 https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.
Submit written requests for single copies of this guidance to the
Division of Drug Information, 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 that office in processing
your requests. The guidance may also be obtained by mail by calling
CBER at 800-835-4709 or 240-402-8010. See the SUPPLEMENTARY INFORMATION
section for electronic access to the guidance document.
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: Amanda Roache, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 1176, Silver Spring, MD 20993-0002, 301-796-4548.
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
[[Page 34538]]
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 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
for human use among regulators around the world. The six founding
members of the ICH 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; and the Pharmaceutical
Research and Manufacturers of America. The Standing Members of the ICH
Association include Health Canada and Swissmedic. Any party eligible as
a Member in accordance with the ICH Articles of Association can apply
for membership in writing to the ICH Secretariat. The ICH Secretariat,
which coordinates the preparation of documentation, operates as an
international nonprofit organization and is funded by the Members of
the ICH Association. The ICH Assembly is the overarching body of the
Association and includes representatives from each of the ICH members
and observers.
In the Federal Register of December 24, 1997 (62 FR 67377), FDA
published a notice announcing the availability of the ICH guidance for
industry entitled ``Q3C Impurities: Residual Solvents.'' The guidance
makes recommendations as to what amounts of residual solvents are
considered 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 for new
solvents and PDEs that 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, available at https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073395.pdf. The ``Q3C: Tables and List'' has been updated as of
January 2017 to include the recommended PDE for triethylamine and
methylisobutylketone.
In the Federal Register of October 16, 2015 (80 FR 62537), FDA
published a notice announcing the availability of draft recommendations
for the PDEs for two solvents, trimethylamine and methylisobutylketone,
according to the maintenance procedures for the guidance entitled ``Q3C
Impurities: Residual Solvents,'' available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm073394.pdf. The notice gave interested persons an opportunity to
submit comments by December 15, 2015. After consideration of the
comments received and revisions to the guidance, a final draft of the
recommendations was submitted to the ICH Assembly and endorsed by the
regulatory agencies in November 2016.
The guidance provides a new PDE for the solvent trimethylamine and
a revised PDE for the solvent methylisobutylketone. In addition, the
data used to derive the PDEs are summarized. Revisions made to the
final guidance as a result of comments include a modification of the
PDE for methylisobutylketone from 22.6 milligrams (mg)/day to 45 mg/day
based on reconsideration of the severity of effects identified in rat
studies and the human relevance of effects identified in mouse
carcinogenicity study. The recommendation to place methylisobutylketone
into class 2 remains. The ``Q3C: Tables and List'' has been updated as
of January 2017 to include the recommended PDE for triethylamine and
methylisobutylketone.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Q3C Impurities: Residual Solvents.'' It
does not establish any rights for any person and is 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
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
https://www.regulations.gov.
Dated: July 18, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-15537 Filed 7-24-17; 8:45 am]
BILLING CODE 4164-01-P