Q3C(R8) Impurities: Guidance for Residual Solvents; International Council for Harmonisation; Guidance for Industry; Availability, 70850-70852 [2021-26889]
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Federal Register / Vol. 86, No. 236 / Monday, December 13, 2021 / Notices
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document (eCTD) hierarchy and is
included in Module 1 of an ANDA
submission.
The cover letter provides an overview
of the submission and helps FDA ensure
that the submission is properly triaged
and assigned to the appropriate
assessors. In an effort to ensure that
submissions are effectively managed by
FDA and acted upon within the
performance review goal dates set by the
Generic Drug User Fee Amendments,
FDA has developed cover letter
attachments to accompany, not replace,
applicants’ cover letters for common
submissions, including controlled
correspondence, original ANDAs and
amendments to ANDAs, as well as
supplements to approved ANDAs.
These cover letter attachments have
been designed as a checklist to reflect
common types of information applicants
are expected to address in their cover
letters. The attachments are intended
both to serve as a useful guide to help
applicants prepare their cover letters,
and to assist FDA in the triage and
management of submissions.
This draft guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The draft guidance, when finalized, will
represent the current thinking of FDA
on ‘‘Cover Letter Attachments for
Controlled Correspondences and ANDA
Submissions.’’ 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. Paperwork Reduction Act of 1995
While this guidance contains no
collection of information, it does refer to
previously approved FDA collections of
information. Therefore, clearance by the
Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501–
3521) is not required for this guidance.
The previously approved collections of
information are subject to review by
OMB under the PRA. The collections of
information in 21 CFR part 314
(including subpart C) for to the content
and format of ANDAs, including
original ANDAs, amendments to
ANDAs, and supplements to approved
ANDAs, submitted by applicants and
approved by FDA have been approved
under OMB control number 0910–0001.
The collections of information for Form
FDA 356h (NDA and ANDA cover letter)
have been approved under OMB control
number 0910–0338.
Applicants submit to FDA controlled
correspondence along with cover letters
related to generic drug development and
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FDA approval. Such submissions have
been approved under OMB control
number 0910–0797. The collections of
information in 21 CFR part 11 for
electronic records and electronic
signatures have been approved under
OMB control number 0910–0303. The
collections of information in 21 CFR
part 211 about the manufacture of the
drug have been approved under OMB
control number 0910–0139.
III. Electronic Access
Persons with access to the internet
may obtain the draft guidance at https://
www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, https://www.fda.gov/
regulatory-information/search-fdaguidance-documents, or https://
www.regulations.gov.
Dated: December 6, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021–26893 Filed 12–10–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2020–D–1301]
Q3C(R8) Impurities: Guidance for
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 a final
guidance for industry entitled ‘‘Q3C(R8)
Impurities: Guidance for Residual
Solvents.’’ The guidance was prepared
under the auspices of the International
Council for Harmonisation (ICH),
formerly the International Conference
on Harmonisation. This guidance
provides recommendations for
permitted daily exposures (PDEs) for
three additional residual solvents: 2Methyltetrahydrofuran, cyclopentyl
methyl ether, and tert-butyl alcohol. The
PDEs were developed according to the
methods for establishing exposure limits
included in the guidance for industry
‘‘Q3C: Impurities Residual Solvents’’
(Q3C guidance). The Q3C PDE levels are
added and revised as new toxicological
data for solvents become available. This
guidance finalizes the draft guidance
entitled ‘‘Q3C(R8) Recommendations for
the Permitted Daily Exposures for Three
Solvents—2-Methyltetrahydrofuran,
SUMMARY:
PO 00000
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Cyclopentyl Methyl Ether, and TertButyl Alcohol—According to the
Maintenance Procedures for the
Guidance Q3C Impurities: Residual
Solvents’’ issued on May 27, 2020.
DATES: The announcement of the
guidance is published in the Federal
Register on December 13, 2021.
ADDRESSES: You may submit either
electronic or written comments on
Agency guidances at any time 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–
2020–D–1301 for ‘‘Q3C(R8) Impurities:
Guidance for Residual Solvents.’’
Received comments will be placed in
the docket and, except for those
submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
E:\FR\FM\13DEN1.SGM
13DEN1
khammond on DSKJM1Z7X2PROD with NOTICES
Federal Register / Vol. 86, No. 236 / Monday, December 13, 2021 / Notices
https://www.regulations.gov or at the
Dockets Management Staff between 9
a.m. and 4 p.m., Monday through
Friday, 240–402–7500.
• 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.govinfo.gov/content/pkg/FR-201509-18/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, 240–402–7500.
You may submit comments on any
guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single
copies of this guidance to the Division
of Drug Information, Center for Drug
Evaluation and Research, 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
VerDate Sep<11>2014
16:50 Dec 10, 2021
Jkt 256001
your requests. The guidance 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 guidance
document.
FOR FURTHER INFORMATION CONTACT:
Regarding the guidance: Timothy
McGovern, Center for Drug Evaluation
and Research, Food and Drug
Administration, Bldg. 22, Rm. 6426,
Silver Spring, MD 20993–0002, 240–
402–0477; or Stephen Ripley, Center for
Biologics Evaluation and Research,
Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 71, Rm.
7301, Silver Spring, MD 20993–0002,
240–402–7911.
Regarding the ICH: Jill Adleberg,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 6364, Silver Spring,
MD 20993–0002, 301–796–5259,
Jill.Adleberg@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled
‘‘Q3C(R8) Impurities: Guideline for
Residual Solvents.’’ The guidance was
prepared under the auspices of ICH. ICH
has the mission of achieving greater
regulatory harmonization worldwide to
ensure that safe, effective, high-quality
medicines are developed, registered,
and maintained in the most resourceefficient manner. By harmonizing the
regulatory requirements in regions
around the world, ICH guidelines have
substantially reduced duplicative
clinical studies, prevented unnecessary
animal studies, standardized the
reporting of important safety
information, standardized marketing
application submissions, and made
many other improvements in the quality
of global drug development and
manufacturing and the products
available to patients.
The six Founding Members of the ICH
are FDA; the Pharmaceutical Research
and Manufacturers of America; the
European Commission; the European
Federation of Pharmaceutical Industries
Associations; the Japanese Ministry of
Health, Labour, and Welfare; and the
Japanese Pharmaceutical Manufacturers
Association. The Standing Members of
the ICH Association include Health
Canada and Swissmedic. Additionally,
the Membership of ICH has expanded to
include other regulatory authorities and
industry associations from around the
world (refer to https://www.ich.org/).
ICH works by involving technical
experts from both regulators and
PO 00000
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70851
industry parties in detailed technical
harmonization work and the application
of a science-based approach to
harmonization through a consensusdriven process that results in the
development of ICH guidelines. The
regulators around the world are
committed to consistently adopting
these consensus-based guidelines,
realizing the benefits for patients and for
industry.
As a Founding Regulatory Member of
ICH, FDA plays a major role in the
development of each of the ICH
guidelines, which FDA then adopts and
issues as guidance for industry. FDA’s
guidance documents do not establish
legally enforceable responsibilities.
Instead, they describe the Agency’s
current thinking on a topic and should
be viewed only as recommendations,
unless specific regulatory or statutory
requirements are cited.
In the Federal Register of May 27,
2020 (85 FR 31785), FDA published a
notice announcing the availability of a
draft guidance entitled ‘‘Q3C(R8)
Recommendations for the Permitted
Daily Exposures for Three Solvents—2Methyltetrahydrofuran, Cyclopentyl
Methyl Ether, and Tert-Butyl Alcohol—
According to the Maintenance
Procedures for the Guidance Q3C
Impurities: Residual Solvents.’’ The
notice gave interested persons an
opportunity to submit comments. In the
Federal Register of June 5, 2020 (85 FR
34638), FDA issued a correction
providing that the date by which to
submit comments was July 27, 2020.
After consideration of the comments
received and revisions to the guideline,
a final draft of the guideline was
submitted to the ICH Assembly and
endorsed by the regulatory agencies in
April 2021.
First published in December 1997, the
Q3C guidance provides
recommendations on the use of less
toxic solvents in the manufacture of
drug substances and dosage forms and
sets pharmaceutical limits for residual
solvents (organic volatile chemicals) in
drug products. Q3C PDE levels are
added and revised as new toxicological
data for solvents become available. As
part of the maintenance process, the
Q3C(R8) guidance provides final PDEs
for three additional residual solvents: 2methyltetrahydrofuran, cyclopentyl
methyl ether, and tert-butyl alcohol.
Additional information regarding
supporting studies was incorporated
into the guidance based on comments
received, but the recommended PDEs
for the three new residual solvents are
identical to those published in the draft
guidance issued on May 27, 2020. This
E:\FR\FM\13DEN1.SGM
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70852
Federal Register / Vol. 86, No. 236 / Monday, December 13, 2021 / Notices
guidance finalizes the guidance issued
on May 27, 2020.
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(R8)
Impurities: Guidance for 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. Paperwork Reduction Act of 1995
While this guidance contains no
collection of information, it does refer to
previously approved FDA collections of
information. Therefore, clearance by the
Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501–
3521) is not required for this guidance.
The previously approved collections of
information are subject to review by
OMB under the PRA. The collections of
information in 21 CFR part 58 have been
approved under OMB control number
0910–0119.
Dated: December 6, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021–26889 Filed 12–10–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2021–N–1287]
Actavis LLC, et al.; Withdrawal of
Approval of Six Abbreviated New Drug
Applications
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
III. Electronic Access
Persons with access to the internet
may obtain the guidance at https://
khammond on DSKJM1Z7X2PROD with NOTICES
www.regulations.gov, https://
www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, https://www.fda.gov/
regulatory-information/search-fdaguidance-documents, or https://
www.fda.gov/vaccines-blood-biologics/
guidance-compliance-regulatoryinformation-biologics/biologicsguidances.
Notice.
The Food and Drug
Administration (FDA or Agency) is
SUMMARY:
Application No.
Drug
ANDA 202603 ...........
Methoxsalen Capsules, 10 milligrams (mg) ...........
ANDA 205274 ...........
Amoxicillin Tablets, 125 mg and 250 mg ...............
ANDA 205513 ...........
Carisoprodol Tablets, 250 mg and 350 mg ............
ANDA 206410 ...........
ANDA 207536 ...........
ANDA 208227 ...........
Itraconazole Capsules, 100 mg ..............................
Flucytosine Capsules, 250 mg and 500 mg ...........
Dutasteride Capsules, 0.5 mg ................................
Therefore, approval of the
applications listed in the table, and all
amendments and supplements thereto,
is hereby withdrawn as of January 12,
2022. Approval of each entire
application is withdrawn, including any
strengths and dosage forms
inadvertently missing from the table.
Introduction or delivery for introduction
into interstate commerce of products
without approved new drug
applications violates section 301(a) and
(d) of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 331(a) and (d)).
Drug products that are listed in the table
that are in inventory on January 12,
2022, may continue to be dispensed
until the inventories have been depleted
or the drug products have reached their
VerDate Sep<11>2014
16:50 Dec 10, 2021
Jkt 256001
Approval is withdrawn as of
January 12, 2022.
DATES:
FOR FURTHER INFORMATION CONTACT:
Martha Nguyen, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 1676,
Silver Spring, MD 20993–0002, 240–
402–6980, Martha.Nguyen@fda.hhs.gov.
The
applicants listed in the table have
informed FDA that these drug products
are no longer marketed and have
requested that FDA withdraw approval
of the applications under the process
described in § 314.150(c) (21 CFR
314.150(c)). The applicants have also,
by their requests, waived their
opportunity for a hearing. Withdrawal
of approval of an application or
abbreviated application under
§ 314.150(c) is without prejudice to
refiling.
SUPPLEMENTARY INFORMATION:
Applicant
Actavis LLC, (an indirect, wholly owned subsidiary of Teva Pharmaceuticals USA, Inc.), 400 Interpace Pkwy., Bldg. A, Parsippany, NJ 07054.
Hikma Pharmaceuticals LLC, 1809 Wilson Rd., Columbus, OH
43228.
Strides Pharma Global Pte. Limited, U.S. Agent, Strides Pharma
Inc., 2 Tower Center Blvd., Suite 1102, East Brunswick, NJ
08816.
Do.
Do.
Do.
expiration dates or otherwise become
violative, whichever occurs first.
Dated: December 7, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021–26892 Filed 12–10–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Single-Source Supplement for Title X
Services in Texas
Office of Population Affairs,
Office of the Assistant Secretary for
Health, Office of the Secretary,
Department of Health and Human
Services (HHS).
AGENCY:
PO 00000
withdrawing approval of six abbreviated
new drug applications (ANDAs) from
multiple applicants. The applicants
notified the Agency in writing that the
drug products were no longer marketed
and requested that the approval of the
applications be withdrawn.
Frm 00039
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ACTION:
Notice.
The Office of Population
Affairs (OPA) announces the award of a
single-source supplement to provide
Title X family planning services in
Texas to Women’s Health and Family
Planning Association of Texas (d.b.a.
Every Body Texas). The supplement
will enable Every Body Texas to expand
provision of emergency contraception
and other family planning services to
clients across the state of Texas to
address the anticipated increased
demand for family planning services
following passage of TX SB8.
DATES: December 13, 2021.
FOR FURTHER INFORMATION CONTACT:
Jessica Swafford Marcella, Deputy
Assistant Secretary for Population
SUMMARY:
E:\FR\FM\13DEN1.SGM
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]]>Agencies
[Federal Register Volume 86, Number 236 (Monday, December 13, 2021)]
[Notices]
[Pages 70850-70852]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-26889]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-1301]
Q3C(R8) Impurities: Guidance for 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 a final guidance for industry entitled ``Q3C(R8)
Impurities: Guidance for Residual Solvents.'' The guidance was prepared
under the auspices of the International Council for Harmonisation
(ICH), formerly the International Conference on Harmonisation. This
guidance provides recommendations for permitted daily exposures (PDEs)
for three additional residual solvents: 2-Methyltetrahydrofuran,
cyclopentyl methyl ether, and tert-butyl alcohol. The PDEs were
developed according to the methods for establishing exposure limits
included in the guidance for industry ``Q3C: Impurities Residual
Solvents'' (Q3C guidance). The Q3C PDE levels are added and revised as
new toxicological data for solvents become available. This guidance
finalizes the draft guidance entitled ``Q3C(R8) Recommendations for the
Permitted Daily Exposures for Three Solvents--2-Methyltetrahydrofuran,
Cyclopentyl Methyl Ether, and Tert-Butyl Alcohol--According to the
Maintenance Procedures for the Guidance Q3C Impurities: Residual
Solvents'' issued on May 27, 2020.
DATES: The announcement of the guidance is published in the Federal
Register on December 13, 2021.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time 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-2020-D-1301 for ``Q3C(R8) Impurities: Guidance for Residual
Solvents.'' Received comments will be placed in the docket and, except
for those submitted as ``Confidential Submissions,'' publicly viewable
at
[[Page 70851]]
https://www.regulations.gov or at the Dockets Management Staff between
9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
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.govinfo.gov/content/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, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
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 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT:
Regarding the guidance: Timothy McGovern, Center for Drug
Evaluation and Research, Food and Drug Administration, Bldg. 22, Rm.
6426, Silver Spring, MD 20993-0002, 240-402-0477; or Stephen Ripley,
Center for Biologics Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver
Spring, MD 20993-0002, 240-402-7911.
Regarding the ICH: Jill Adleberg, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-5259,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Q3C(R8) Impurities: Guideline for Residual Solvents.'' The
guidance was prepared under the auspices of ICH. ICH has the mission of
achieving greater regulatory harmonization worldwide to ensure that
safe, effective, high-quality medicines are developed, registered, and
maintained in the most resource-efficient manner. By harmonizing the
regulatory requirements in regions around the world, ICH guidelines
have substantially reduced duplicative clinical studies, prevented
unnecessary animal studies, standardized the reporting of important
safety information, standardized marketing application submissions, and
made many other improvements in the quality of global drug development
and manufacturing and the products available to patients.
The six Founding Members of the ICH are FDA; the Pharmaceutical
Research and Manufacturers of America; the European Commission; the
European Federation of Pharmaceutical Industries Associations; the
Japanese Ministry of Health, Labour, and Welfare; and the Japanese
Pharmaceutical Manufacturers Association. The Standing Members of the
ICH Association include Health Canada and Swissmedic. Additionally, the
Membership of ICH has expanded to include other regulatory authorities
and industry associations from around the world (refer to https://www.ich.org/).
ICH works by involving technical experts from both regulators and
industry parties in detailed technical harmonization work and the
application of a science-based approach to harmonization through a
consensus-driven process that results in the development of ICH
guidelines. The regulators around the world are committed to
consistently adopting these consensus-based guidelines, realizing the
benefits for patients and for industry.
As a Founding Regulatory Member of ICH, FDA plays a major role in
the development of each of the ICH guidelines, which FDA then adopts
and issues as guidance for industry. FDA's guidance documents do not
establish legally enforceable responsibilities. Instead, they describe
the Agency's current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory requirements
are cited.
In the Federal Register of May 27, 2020 (85 FR 31785), FDA
published a notice announcing the availability of a draft guidance
entitled ``Q3C(R8) Recommendations for the Permitted Daily Exposures
for Three Solvents--2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether,
and Tert-Butyl Alcohol--According to the Maintenance Procedures for the
Guidance Q3C Impurities: Residual Solvents.'' The notice gave
interested persons an opportunity to submit comments. In the Federal
Register of June 5, 2020 (85 FR 34638), FDA issued a correction
providing that the date by which to submit comments was July 27, 2020.
After consideration of the comments received and revisions to the
guideline, a final draft of the guideline was submitted to the ICH
Assembly and endorsed by the regulatory agencies in April 2021.
First published in December 1997, the Q3C guidance provides
recommendations on the use of less toxic solvents in the manufacture of
drug substances and dosage forms and sets pharmaceutical limits for
residual solvents (organic volatile chemicals) in drug products. Q3C
PDE levels are added and revised as new toxicological data for solvents
become available. As part of the maintenance process, the Q3C(R8)
guidance provides final PDEs for three additional residual solvents: 2-
methyltetrahydrofuran, cyclopentyl methyl ether, and tert-butyl
alcohol. Additional information regarding supporting studies was
incorporated into the guidance based on comments received, but the
recommended PDEs for the three new residual solvents are identical to
those published in the draft guidance issued on May 27, 2020. This
[[Page 70852]]
guidance finalizes the guidance issued on May 27, 2020.
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(R8) Impurities: Guidance for 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. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 58 have been approved under OMB control
number 0910-0119.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.
Dated: December 6, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021-26889 Filed 12-10-21; 8:45 am]
BILLING CODE 4164-01-P
