[Federal Register Volume 80, Number 83 (Thursday, April 30, 2015)]
[Notices]
[Pages 24257-24258]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-10063]



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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.

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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draft guidance issued in February 2012.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\
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    \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).
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    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:
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    \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.
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     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

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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