80 FR 24257 - Guidance for Industry on Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 83 (April 30, 2015)

Page Range		24257-24258
FR Document		2015-10063

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product.'' This guidance is intended to provide sponsors with an overview of analytical factors that are relevant to assessing whether a proposed product and the reference product are highly similar for the purpose of submitting a marketing application through an abbreviated licensure pathway. This guidance finalizes the draft guidance issued in February 2012.

Federal Register, Volume 80 Issue 83 (Thursday, April 30, 2015)

[Federal Register Volume 80, Number 83 (Thursday, April 30, 2015)]
[Notices]
[Pages 24257-24258]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2015-10063]

[[Page 24257]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0602]

Guidance for Industry on Quality Considerations in Demonstrating
Biosimilarity of a Therapeutic Protein Product to a Reference Product;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a guidance for industry entitled ``Quality
Considerations in Demonstrating Biosimilarity of a Therapeutic Protein
Product to a Reference Product.'' This guidance is intended to provide
sponsors with an overview of analytical factors that are relevant to
assessing whether a proposed product and the reference product are
highly similar for the purpose of submitting a marketing application
through an abbreviated licensure pathway. This guidance finalizes the
draft guidance issued in February 2012.

DATES: Submit either electronic or written comments on Agency guidances
at any time.

ADDRESSES: 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, 10903 New Hampshire Ave., Bldg.
51, Rm. 2201, Silver Spring, MD 20993-0002 or the Office of
Communication, Outreach and Development (HFM-40), Center for Biologics
Evaluation and Research (CBER), Food and 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. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.
Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Sandra Benton, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6340, Silver Spring, MD 20993-0002, 301-
796-1042, 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.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry
entitled ``Quality Considerations in Demonstrating Biosimilarity of a
Therapeutic Protein Product to a Reference Product.'' This guidance is
intended to provide sponsors with an overview of analytical factors
that are relevant to assessing whether a proposed product and the
reference product are highly similar for the purpose of submitting a
marketing application through the abbreviated licensure pathway under
section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C.
262(k)). Although the 351(k) pathway applies generally to biological
products, this guidance focuses on therapeutic protein products.
The Biologics Price Competition and Innovation Act of 2009 was
enacted as part of the Patient Protection and Affordable Care Act (Pub.
L. 111-148) on March 23, 2010, created an abbreviated licensure pathway
under section 351(k) of the PHS Act for biological products
demonstrated to be biosimilar to or interchangeable with a reference
product. Under this abbreviated licensure pathway, FDA will license a
proposed biological product submitted under section 351(k) of the PHS
Act if FDA ``determines that the information submitted in the
application . . . is sufficient to show that the biological product . .
. is biosimilar to the reference product . . .'' and the 351(k)
applicant (or other appropriate person) consents to an inspection of
the facility that is the subject of the application (i.e., a facility
in which the proposed biological product is manufactured, processed,
packed, or held).\1\
---------------------------------------------------------------------------

\1\ Section 7002(a)(2) of the Affordable Care Act, adding
section 351(k)(3) of the PHS Act (citing section 351(a)(2)(C) of the
PHS Act).
---------------------------------------------------------------------------

All product applications should contain a complete and thorough
chemistry, manufacturing, and controls section that provides the
necessary and appropriate information, including, but not limited to,
characterization, adventitious agent safety, process controls, and
specifications, for the product to be adequately reviewed.\2\ This
guidance describes important factors for consideration when assessing
whether a proposed product and the reference product are highly
similar, including:
---------------------------------------------------------------------------

\2\ For CMC requirements for submission of a marketing
application, applicants should consult current regulations, the
guidance for industry for the ``Submission of Chemistry,
Manufacturing, and Controls Information for a Therapeutic
Recombinant DNA-Derived Product or a Monoclonal Antibody Product for
In-Vivo Use,'' and other applicable FDA guidance documents.
---------------------------------------------------------------------------

Expression System
Manufacturing Process
Assessment of Physiochemical Properties
Functional Activities
Receptor Binding and Immunochemical Properties
Impurities
Reference Product and Reference Standards
Finished Drug Product
Stability
In the Federal Register of February 15, 2012 (77 FR 8884), FDA
announced the availability of the draft guidance entitled ``Quality
Considerations in Demonstrating Biosimilarity to a Reference Protein
Product'' dated February 2012. FDA received a number of comments on the
draft guidance. In response to these comments, this guidance provides
further clarification on general principles on topics including, but
not limited to, the use of comparative analytical data to provide the
foundation for a biosimilar development program, the timing of
submission of analytical similarity data, the appropriate number of
lots needed, and the type of bridging data needed when sponsors use a
non-U.S.-licensed comparator product in certain studies. The guidance
provides additional clarification on the factors for consideration in
assessing whether a proposed product is highly similar to the reference
product. This guidance finalizes the draft guidance issued in February
2012.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
Agency's current thinking on quality considerations in demonstrating
biosimilarity of a therapeutic protein product to a reference product.
It does not create or confer any rights for or on any person and does
not operate to bind FDA or the public. An alternative approach may be
used if such approach satisfies the requirements of the applicable
statutes and regulations.

II. Comments

Interested persons may submit either electronic comments regarding
this document to http://www.regulations.gov or written comments to the
Division of Dockets Management (see ADDRESSES). It

[[Page 24258]]

is only necessary to send one set of comments. Identify comments with
the docket number found in brackets in the heading of this document.
Received comments may be seen in the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to
the docket at http://www.regulations.gov.

III. The Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of
information found in FDA regulations, which are not expected to change
as a result of the guidance. These collections of information are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The
collections of information related to the submission of: (1) An
investigational new drug application, which is covered under 21 CFR
part 312 and approved under OMB control number 0910-0014; (2) a new
drug application, which is covered under 21 CFR 314.50 and approved
under OMB control number 0910-0001; (3) a biologics license application
(BLA) under section 351(a) of the PHS Act, which is covered under part
601 (21 CFR part 601) and approved under OMB control number 0910-0338;
and (4) a BLA under section 351(k), which is covered under part 601 and
approved under OMB control number 0910-0719.

IV. Electronic Access

Persons with access to the Internet may obtain the document at
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm, or http://www.regulations.gov.

Dated: April 24, 2015.
Peter Lurie,
Associate Commissioner for Public Health Strategy and Analysis.
[FR Doc. 2015-10063 Filed 4-29-15; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 80, No. 83 / Thursday, April 30, 2015 / Notices 24257

DEPARTMENT OF HEALTH AND Biologics Evaluation and Research, This guidance describes important
HUMAN SERVICES Food and Drug Administration, 10903 factors for consideration when assessing
New Hampshire Ave., Bldg. 71, Rm. whether a proposed product and the
Food and Drug Administration 7301, Silver Spring, MD 20993–0002, reference product are highly similar,
[Docket No. FDA–2011–D–0602] 240–402–7911. including:
SUPPLEMENTARY INFORMATION: • Expression System
Guidance for Industry on Quality • Manufacturing Process
I. Background • Assessment of Physiochemical
Considerations in Demonstrating
Biosimilarity of a Therapeutic Protein FDA is announcing the availability of Properties
Product to a Reference Product; a guidance for industry entitled • Functional Activities
Availability ‘‘Quality Considerations in • Receptor Binding and
Demonstrating Biosimilarity of a Immunochemical Properties
AGENCY: Food and Drug Administration, Therapeutic Protein Product to a • Impurities
HHS. Reference Product.’’ This guidance is • Reference Product and Reference
ACTION: Notice. intended to provide sponsors with an Standards
overview of analytical factors that are • Finished Drug Product
SUMMARY: The Food and Drug relevant to assessing whether a • Stability
Administration (FDA) is announcing the proposed product and the reference In the Federal Register of February
availability of a guidance for industry product are highly similar for the 15, 2012 (77 FR 8884), FDA announced
entitled ‘‘Quality Considerations in purpose of submitting a marketing the availability of the draft guidance
Demonstrating Biosimilarity of a application through the abbreviated entitled ‘‘Quality Considerations in
Therapeutic Protein Product to a licensure pathway under section 351(k) Demonstrating Biosimilarity to a
Reference Product.’’ This guidance is of the Public Health Service Act (PHS Reference Protein Product’’ dated
intended to provide sponsors with an Act) (42 U.S.C. 262(k)). Although the February 2012. FDA received a number
overview of analytical factors that are 351(k) pathway applies generally to of comments on the draft guidance. In
relevant to assessing whether a biological products, this guidance response to these comments, this
proposed product and the reference focuses on therapeutic protein products. guidance provides further clarification
product are highly similar for the The Biologics Price Competition and on general principles on topics
purpose of submitting a marketing Innovation Act of 2009 was enacted as including, but not limited to, the use of
application through an abbreviated part of the Patient Protection and comparative analytical data to provide
licensure pathway. This guidance Affordable Care Act (Pub. L. 111–148) the foundation for a biosimilar
finalizes the draft guidance issued in on March 23, 2010, created an development program, the timing of
February 2012. abbreviated licensure pathway under submission of analytical similarity data,
DATES: Submit either electronic or section 351(k) of the PHS Act for the appropriate number of lots needed,
written comments on Agency guidances biological products demonstrated to be and the type of bridging data needed
at any time. biosimilar to or interchangeable with a when sponsors use a non-U.S.-licensed
ADDRESSES: Submit written requests for reference product. Under this comparator product in certain studies.
single copies of this guidance to the abbreviated licensure pathway, FDA The guidance provides additional
Division of Drug Information, Center for will license a proposed biological clarification on the factors for
Drug Evaluation and Research, Food product submitted under section 351(k) consideration in assessing whether a
and Drug Administration, 10903 New of the PHS Act if FDA ‘‘determines that proposed product is highly similar to
Hampshire Ave., Bldg. 51, Rm. 2201, the information submitted in the the reference product. This guidance
Silver Spring, MD 20993–0002 or the application . . . is sufficient to show finalizes the draft guidance issued in
Office of Communication, Outreach and that the biological product . . . is February 2012.
Development (HFM–40), Center for biosimilar to the reference product . . .’’ This guidance is being issued
Biologics Evaluation and Research and the 351(k) applicant (or other consistent with FDA’s good guidance
(CBER), Food and Administration, appropriate person) consents to an practices regulation (21 CFR 10.115).
10903 New Hampshire Ave., Bldg. 71, inspection of the facility that is the The guidance represents the Agency’s
Rm. 3128, Silver Spring, MD 20993– subject of the application (i.e., a facility current thinking on quality
0002. Send one self-addressed adhesive in which the proposed biological considerations in demonstrating
label to assist that office in processing product is manufactured, processed, biosimilarity of a therapeutic protein
your requests. See the SUPPLEMENTARY packed, or held).1 product to a reference product. It does
INFORMATION section for electronic
All product applications should not create or confer any rights for or on
access to the guidance document. contain a complete and thorough any person and does not operate to bind
Submit electronic comments on the chemistry, manufacturing, and controls FDA or the public. An alternative
guidance to http://www.regulations.gov. section that provides the necessary and approach may be used if such approach
Submit written comments to the appropriate information, including, but satisfies the requirements of the
Division of Dockets Management (HFA– not limited to, characterization, applicable statutes and regulations.
305), Food and Drug Administration, adventitious agent safety, process
controls, and specifications, for the II. Comments
5630 Fishers Lane, Rm. 1061, Rockville,
MD 20852. product to be adequately reviewed.2 Interested persons may submit either
mstockstill on DSK4VPTVN1PROD with NOTICES

electronic comments regarding this
FOR FURTHER INFORMATION CONTACT: 1 Section 7002(a)(2) of the Affordable Care Act,
document to http://www.regulations.gov
Sandra Benton, Center for Drug adding section 351(k)(3) of the PHS Act (citing
or written comments to the Division of
Evaluation and Research, Food and section 351(a)(2)(C) of the PHS Act).
Dockets Management (see ADDRESSES). It
2 For CMC requirements for submission of a
Drug Administration, 10903 New
marketing application, applicants should consult
Hampshire Ave., Bldg. 51, Rm. 6340, current regulations, the guidance for industry for Recombinant DNA-Derived Product or a
Silver Spring, MD 20993–0002, 301– the ‘‘Submission of Chemistry, Manufacturing, and Monoclonal Antibody Product for In-Vivo Use,’’
796–1042, or Stephen Ripley, Center for Controls Information for a Therapeutic and other applicable FDA guidance documents.

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24258 Federal Register / Vol. 80, No. 83 / Thursday, April 30, 2015 / Notices

is only necessary to send one set of DEPARTMENT OF HEALTH AND 7301, Silver Spring, MD 20993–0002,
comments. Identify comments with the HUMAN SERVICES 240–402–7911.
docket number found in brackets in the SUPPLEMENTARY INFORMATION:
heading of this document. Received Food and Drug Administration
I. Background
comments may be seen in the Division [Docket No. FDA–2011–D–0605]
of Dockets Management between 9 a.m. FDA is announcing the availability of
and 4 p.m., Monday through Friday, and Scientific Considerations in a guidance for industry entitled
will be posted to the docket at http:// Demonstrating Biosimilarity to a ‘‘Scientific Considerations in
www.regulations.gov. Reference Product; Guidance for Demonstrating Biosimilarity to a
Industry; Availability Reference Product.’’ This guidance is
III. The Paperwork Reduction Act of intended to assist sponsors in
1995 AGENCY: Food and Drug Administration, demonstrating that a proposed
HHS. therapeutic protein product is
This guidance refers to previously ACTION: Notice. ‘‘biosimilar’’ 1 to a reference product for
approved collections of information the purpose of submitting a marketing
found in FDA regulations, which are not SUMMARY: The Food and Drug application through the abbreviated
expected to change as a result of the Administration (FDA) is announcing the licensure pathway under section 351(k)
guidance. These collections of availability of a guidance for industry of the Public Health Service Act (PHS
information are subject to review by the entitled ‘‘Scientific Considerations in Act) (42 U.S.C. 262(k)).
Office of Management and Budget Demonstrating Biosimilarity to a The Biologics Price Competition and
(OMB) under the Paperwork Reduction Reference Product.’’ This guidance is Innovation Act of 2009 (BPCI Act),
Act of 1995 (44 U.S.C. 3501–3520). The intended to assist sponsors in enacted as part of the Affordable Care
collections of information related to the demonstrating that a proposed Act (Pub. L. 111–148) on March 23,
submission of: (1) An investigational therapeutic protein product is 2010, created an abbreviated licensure
biosimilar to a reference product for the pathway under section 351(k) of the
new drug application, which is covered
purpose of submitting a marketing PHS Act for biological products
under 21 CFR part 312 and approved
application through an abbreviated demonstrated to be biosimilar to, or
under OMB control number 0910–0014; licensure pathway. This guidance gives interchangeable with, a reference
(2) a new drug application, which is an overview of FDA’s approach to product. Under this abbreviated
covered under 21 CFR 314.50 and determining biosimilarity. licensure pathway, FDA will license a
approved under OMB control number proposed biological product submitted
DATES: Submit either electronic or
0910–0001; (3) a biologics license under section 351(k) of the PHS Act if
written comments on Agency guidances
application (BLA) under section 351(a) at any time. FDA ‘‘determines that the information
of the PHS Act, which is covered under submitted in the application . . . is
ADDRESSES: Submit written requests for
part 601 (21 CFR part 601) and sufficient to show that the biological
single copies of the guidance to the
approved under OMB control number product is biosimilar to the reference
Division of Drug Information, Center for
0910–0338; and (4) a BLA under section product. . . .’’ and the 351(k) applicant
Drug Evaluation and Research, Food
351(k), which is covered under part 601 and Drug Administration, 10001 New (or other appropriate person) consents
and approved under OMB control Hampshire Ave., Hillandale Building, to an inspection of the facility that is the
number 0910–0719. 4th Floor, Silver Spring, MD 20993– subject of the application (i.e., a facility
0002, or Office of Communication, in which the proposed biological
IV. Electronic Access product is manufactured, processed,
Outreach, and Development, Center for
Persons with access to the Internet Biologics Evaluation and Research packed, or held).2 The guidance gives an
may obtain the document at either (CBER), Food and Drug Administration, overview of FDA’s approach to
http://www.fda.gov/Drugs/Guidance 10903 New Hampshire Ave., Bldg. 71, determining biosimilarity. FDA intends
Rm. 3128, Silver Spring, MD 20993– to consider the totality of the evidence
ComplianceRegulatoryInformation/
0002. Send one self-addressed adhesive submitted in a 351(k) application and is
Guidances/default.htm, http://www.fda.
label to assist that office in processing recommending that sponsors use a
gov/BiologicsBloodVaccines/Guidance
your requests. See the SUPPLEMENTARY stepwise approach in their development
ComplianceRegulatoryInformation/ of biosimilar products. The guidance
default.htm, or http:// INFORMATION section for electronic
access to the guidance document. discusses important scientific
www.regulations.gov. considerations in demonstrating
Submit electronic comments on the
Dated: April 24, 2015. guidance to http://www.regulations.gov. biosimilarity, including:
Peter Lurie, • A stepwise approach to
Submit written comments to the
demonstrating biosimilarity, which can
Associate Commissioner for Public Health Division of Dockets Management (HFA–
include a comparison of the proposed
Strategy and Analysis. 305), Food and Drug Administration,
product and the reference product with
[FR Doc. 2015–10063 Filed 4–29–15; 8:45 am] 5630 Fishers Lane, Rm. 1061, Rockville,
BILLING CODE 4164–01–P MD 20852. 1 In section 7002(b)(3) of the Patient Protection
FOR FURTHER INFORMATION CONTACT: and Affordable Care Act (Affordable Care Act), Pub.
Sandra Benton, Center for Drug L. 111–148, ‘‘biosimilar’’ or ‘‘biosimilarity’’ means
‘‘that the biological product is highly similar to the
mstockstill on DSK4VPTVN1PROD with NOTICES

Evaluation and Research, Food and
reference product notwithstanding minor
Drug Administration, 10903 New differences in clinically inactive components,’’ and
Hampshire Ave., Bldg. 51, Rm. 6340, that ‘‘there are no clinically meaningful differences
Silver Spring, MD 20993–0002, 301– between the biological product and the reference
796–1042, or Stephen Ripley, Center for product in terms of the safety, purity, and potency
of the product.’’
Biologics Evaluation and Research, 2 Section 7002(a)(2) of the Affordable Care Act,
Food and Drug Administration, 10903 adding section 351(k)(3) of the PHS Act (citing
New Hampshire Ave., Bldg. 71, Rm. section 351(a)(2)(C) of the PHS Act).

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Document Created: 2018-02-21 10:14:50
Document Modified: 2018-02-21 10:14:50

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
Dates		Submit either electronic or written comments on Agency guidances at any time.
Contact		Sandra Benton, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6340, Silver Spring, MD 20993-0002, 301- 796-1042, 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.
FR Citation		80 FR 24257

80 FR 24257 - Guidance for Industry on Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 83 (April 30, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration