M9 Biopharmaceutics Classification System-Based Biowaivers; International Council for Harmonisation; Guidance for Industry; Availability, 26054-26056 [2021-09962]
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Federal Register / Vol. 86, No. 90 / Wednesday, May 12, 2021 / Notices
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 September 2020, the ICH Assembly
endorsed the draft guidance entitled
‘‘Q3D(R2)—Guideline for Elemental
Impurities’’ and agreed that the
guidance should be made available for
public comment. The draft guidance is
the product of the Quality Expert
Working Group of the ICH. Comments
about this draft guidance will be
considered by FDA and the Quality
Expert Working Group.
The draft guidance provides guidance
on PDEs for the cutaneous and
transcutaneous routes of administration
and relevant risk assessment
considerations to supplement previous
guidance for the oral, parenteral, and
inhalation routes of administration. In
addition, error corrections to previously
identified PDEs for gold (oral,
parenteral, and inhalation routes), silver
(parenteral route), and nickel
(inhalation route) are provided.
This draft guidance has been left in
the original ICH format. The final
guidance will be reformatted and edited
to conform with FDA’s good guidance
practices regulation (21 CFR 10.115) and
style before publication. The draft
guidance, when finalized, will represent
the current thinking of FDA on
‘‘Q3D(R2)—Guideline for Elemental
Impurities.’’ 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
FDA tentatively concludes that this
draft guidance contains no collection of
information. Therefore, clearance by the
Office of Management and Budget under
the Paperwork Reduction Act of 1995 is
not required.
khammond on DSKJM1Z7X2PROD with NOTICES
III. Electronic Access
Persons with access to the internet
may obtain the draft guidance at https://
www.regulations.gov, https://
www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, or https://
www.fda.gov/vaccines-blood-biologics/
guidance-compliance-regulatory-
VerDate Sep<11>2014
17:58 May 11, 2021
Jkt 253001
information-biologics/biologicsguidances.
Dated: May 7, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for
Policy.
[FR Doc. 2021–10011 Filed 5–11–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–D–3614]
M9 Biopharmaceutics Classification
System-Based Biowaivers;
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 ‘‘M9
Biopharmaceutics Classification
System-Based Biowaivers.’’ The
guidance was prepared under the
auspices of the International Council for
Harmonisation of Technical
Requirements for Pharmaceuticals for
Human Use (ICH), formerly the
International Conference on
Harmonisation of Technical
Requirements for Registration of
Pharmaceuticals for Human Use. The
guidance provides recommendations to
support the biopharmaceutics
classification of drug substances and the
Biopharmaceutics Classification System
(BCS)-based waiver of the in vivo
bioequivalence (BE) study requirement
for certain drug products. The guidance
is intended to avoid or reduce the need
for human BE trials based on extensive
in vitro characterization of the drug
substance and drug product properties.
The guidance replaces the existing FDA
guidance issued December 26, 2017,
entitled ‘‘Waiver of In Vivo
Bioavailability and Bioequivalence
Studies for Immediate-Release Solid
Oral Dosage Forms Based on a
Biopharmaceutics Classification
System.’’ The guidance also finalizes the
draft ICH guidance, ‘‘M9
Biopharmaceutics Classification
System-Based Biowaivers,’’ issued on
October 26, 2018.
DATES: The announcement of the
guidance is published in the Federal
Register on May 12, 2021.
SUMMARY:
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You may submit either
electronic or written comments on
Agency guidances at any time as
follows:
ADDRESSES:
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–
2018–D–3614 for ‘‘M9
Biopharmaceutics Classification
System-Based Biowaivers.’’ 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, 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
E:\FR\FM\12MYN1.SGM
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khammond on DSKJM1Z7X2PROD with NOTICES
Federal Register / Vol. 86, No. 90 / Wednesday, May 12, 2021 / Notices
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
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: Mehul Mehta,
VerDate Sep<11>2014
17:58 May 11, 2021
Jkt 253001
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 2178, Silver Spring,
MD 20993–0002, 301–796–1573; 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.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled ‘‘M9
Biopharmaceutics Classification
System-Based Biowaivers.’’ 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
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
PO 00000
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26055
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 October 26,
2018 (83 FR 54107), FDA published a
notice announcing the availability of a
draft guidance entitled ‘‘M9
Biopharmaceutics Classification
System-Based Biowaivers.’’ The notice
gave interested persons an opportunity
to submit comments by January 24,
2019.
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 agency
members in November 2019.
The guidance provides
recommendations to support the
biopharmaceutics classification of drug
substances and the BCS-based waiver of
the in vivo BE study requirement for
drug products. The BCS-based
biowaiver approach is intended to
reduce the need for in vivo
bioequivalence studies. In vivo
bioequivalence studies may be waived if
an assumption of equivalence in in vivo
performance can be justified by
satisfactory in vitro data. The BCS is a
scientific approach based on the
aqueous solubility and intestinal
permeability characteristics of the drug
substance or substances. The BCS
categorizes drug substances into one of
four BCS classes as follows:
• Class I: High solubility, high
permeability
• Class II: Low solubility, high
permeability
• Class III: High solubility, low
permeability
• Class IV: Low solubility, low
permeability
In vivo BE studies are needed to
demonstrate lack of impact of
significant formulation changes on a
drug’s bioavailability during its
development, for post approval line
extensions, and when developing a
generic product. Utilizing the critical
properties of the drug substance and the
drug product, and applying the BCS
framework, extensive in vitro studies
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Federal Register / Vol. 86, No. 90 / Wednesday, May 12, 2021 / Notices
can support the waiver of the in vivo BE
requirement for certain drug products.
Following the public consultation
period, clarifications were made to the
guidance based on the comments
received.
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 ‘‘M9
Biopharmaceutics Classification
System-Based Biowaivers.’’ 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.
khammond on DSKJM1Z7X2PROD with NOTICES
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. However, this
final guidance refers to previously
approved FDA collections of
information. The previously approved
collections of information are subject to
review by OMB under the PRA. The
following collections of information
have been approved under OMB control
number 0910–0001:
• Submitting under 21 CFR 314.50
content and format of new drug
applications, including the
pharmacokinetics and bioavailability
sections.
• Submitting under 21 CFR 314.70
postapproval changes.
• Submitting under 21 CFR 314.94
content and format of abbreviated new
drug applications.
The collections of information for
submitting under 21 CFR 312.23
information about pharmacokinetics
and biological disposition of the drug
has been approved under OMB control
number 0910–0014.
III. Electronic Access
Persons with access to the internet
may obtain the guidance at https://
www.regulations.gov, https://
www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm, or https://
www.fda.gov/BiologicsBloodVaccines/
GuidanceComplianceRegulatory
Information/Guidances/default.htm.
Dated: May 6, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for
Policy.
[FR Doc. 2021–09962 Filed 5–11–21; 8:45 am]
BILLING CODE 4164–01–P
VerDate Sep<11>2014
17:58 May 11, 2021
Jkt 253001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–D–4524]
S11 Nonclinical Safety Testing in
Support of Development of Pediatric
Pharmaceuticals; 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 ‘‘S11
Nonclinical Safety Testing in Support of
Development of Pediatric
Pharmaceuticals.’’ The guidance was
prepared under the auspices of the
International Council for Harmonisation
of Technical Requirements for
Registration of Pharmaceuticals for
Human Use (ICH), formerly the
International Conference on
Harmonisation of Technical
Requirements for Registration of
Pharmaceuticals for Human Use. The
guidance recommends international
standards for the nonclinical safety
studies recommended to support the
development of pediatric medicines.
The guidance provides a weight of
evidence approach to determine when
nonclinical toxicity studies may be
recommended in juvenile animals. If
such studies are recommended, the
guidance provides appropriate study
designs. The guidance is intended to
promote harmonization of
recommendations for such studies and
should facilitate the timely conduct of
pediatric clinical trials and reduce the
use of animals in accordance with the
3R (replace/reduce/refine) principles.
Tissue engineered products, gene and
cellular therapies, and vaccines are
excluded from the scope of this
guidance. The guidance replaces the
draft guidance issued on February 1,
2019.
SUMMARY:
The announcement of the
guidance is published in the Federal
Register on May 12, 2021.
ADDRESSES: You may submit either
electronic or written comments on
Agency guidances at any time as
follows:
DATES:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
PO 00000
Frm 00059
Fmt 4703
Sfmt 4703
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–
2018–D–4524 for ‘‘S11 Nonclinical
Safety Testing in Support of
Development of Pediatric
Pharmaceuticals.’’ 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, 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
E:\FR\FM\12MYN1.SGM
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]]>Agencies
[Federal Register Volume 86, Number 90 (Wednesday, May 12, 2021)]
[Notices]
[Pages 26054-26056]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-09962]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-D-3614]
M9 Biopharmaceutics Classification System-Based Biowaivers;
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 ``M9
Biopharmaceutics Classification System-Based Biowaivers.'' The guidance
was prepared under the auspices of the International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human
Use (ICH), formerly the International Conference on Harmonisation of
Technical Requirements for Registration of Pharmaceuticals for Human
Use. The guidance provides recommendations to support the
biopharmaceutics classification of drug substances and the
Biopharmaceutics Classification System (BCS)-based waiver of the in
vivo bioequivalence (BE) study requirement for certain drug products.
The guidance is intended to avoid or reduce the need for human BE
trials based on extensive in vitro characterization of the drug
substance and drug product properties. The guidance replaces the
existing FDA guidance issued December 26, 2017, entitled ``Waiver of In
Vivo Bioavailability and Bioequivalence Studies for Immediate-Release
Solid Oral Dosage Forms Based on a Biopharmaceutics Classification
System.'' The guidance also finalizes the draft ICH guidance, ``M9
Biopharmaceutics Classification System-Based Biowaivers,'' issued on
October 26, 2018.
DATES: The announcement of the guidance is published in the Federal
Register on May 12, 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-2018-D-3614 for ``M9 Biopharmaceutics Classification System-Based
Biowaivers.'' 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, 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
[[Page 26055]]
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: Mehul Mehta,
Center for Drug Evaluation and Research, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 51, Rm. 2178, Silver Spring, MD 20993-
0002, 301-796-1573; 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.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``M9 Biopharmaceutics Classification System-Based
Biowaivers.'' 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 October 26, 2018 (83 FR 54107), FDA
published a notice announcing the availability of a draft guidance
entitled ``M9 Biopharmaceutics Classification System-Based
Biowaivers.'' The notice gave interested persons an opportunity to
submit comments by January 24, 2019.
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 agency members in November
2019.
The guidance provides recommendations to support the
biopharmaceutics classification of drug substances and the BCS-based
waiver of the in vivo BE study requirement for drug products. The BCS-
based biowaiver approach is intended to reduce the need for in vivo
bioequivalence studies. In vivo bioequivalence studies may be waived if
an assumption of equivalence in in vivo performance can be justified by
satisfactory in vitro data. The BCS is a scientific approach based on
the aqueous solubility and intestinal permeability characteristics of
the drug substance or substances. The BCS categorizes drug substances
into one of four BCS classes as follows:
Class I: High solubility, high permeability
Class II: Low solubility, high permeability
Class III: High solubility, low permeability
Class IV: Low solubility, low permeability
In vivo BE studies are needed to demonstrate lack of impact of
significant formulation changes on a drug's bioavailability during its
development, for post approval line extensions, and when developing a
generic product. Utilizing the critical properties of the drug
substance and the drug product, and applying the BCS framework,
extensive in vitro studies
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can support the waiver of the in vivo BE requirement for certain drug
products.
Following the public consultation period, clarifications were made
to the guidance based on the comments received.
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 ``M9 Biopharmaceutics Classification System-
Based Biowaivers.'' 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. However, this final guidance refers to previously approved
FDA collections of information. The previously approved collections of
information are subject to review by OMB under the PRA. The following
collections of information have been approved under OMB control number
0910-0001:
Submitting under 21 CFR 314.50 content and format of new
drug applications, including the pharmacokinetics and bioavailability
sections.
Submitting under 21 CFR 314.70 postapproval changes.
Submitting under 21 CFR 314.94 content and format of
abbreviated new drug applications.
The collections of information for submitting under 21 CFR 312.23
information about pharmacokinetics and biological disposition of the
drug has been approved under OMB control number 0910-0014.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
https://www.regulations.gov, https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
Dated: May 6, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-09962 Filed 5-11-21; 8:45 am]
BILLING CODE 4164-01-P
