
[Federal Register Volume 80, Number 83 (Thursday, April 30, 2015)]
[Notices]
[Pages 24258-24259]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-10062]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0605]


Scientific Considerations in Demonstrating Biosimilarity to a 
Reference Product; Guidance for Industry; 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 ``Scientific 
Considerations in Demonstrating Biosimilarity to a Reference Product.'' 
This guidance is intended to assist sponsors in demonstrating that a 
proposed therapeutic protein product is biosimilar to a reference 
product for the purpose of submitting a marketing application through 
an abbreviated licensure pathway. This guidance gives an overview of 
FDA's approach to determining biosimilarity.

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

ADDRESSES: Submit written requests for single copies of the 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 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. 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 ``Scientific Considerations in Demonstrating Biosimilarity to 
a Reference Product.'' This guidance is intended to assist sponsors in 
demonstrating that a proposed therapeutic protein product is 
``biosimilar'' \1\ to a reference product 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)).
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    \1\ In section 7002(b)(3) of the Patient Protection and 
Affordable Care Act (Affordable Care Act), Pub. L. 111-148, 
``biosimilar'' or ``biosimilarity'' means ``that the biological 
product is highly similar to the reference product notwithstanding 
minor differences in clinically inactive components,'' and that 
``there are no clinically meaningful differences between the 
biological product and the reference product in terms of the safety, 
purity, and potency of the product.''
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    The Biologics Price Competition and Innovation Act of 2009 (BPCI 
Act), enacted as part of the 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).\2\ The 
guidance gives an overview of FDA's approach to determining 
biosimilarity. FDA intends to consider the totality of the evidence 
submitted in a 351(k) application and is recommending that sponsors use 
a stepwise approach in their development of biosimilar products. The 
guidance discusses important scientific considerations in demonstrating 
biosimilarity, including:
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    \2\ 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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     A stepwise approach to demonstrating biosimilarity, which 
can include a comparison of the proposed product and the reference 
product with

[[Page 24259]]

respect to structure, function, animal toxicity, human pharmacokinetics 
(PK) and pharmacodynamics (PD), clinical immunogenicity, and clinical 
safety and effectiveness;
     The totality-of-the-evidence approach that FDA will use to 
review applications for biosimilar products, consistent with a 
longstanding Agency approach to evaluation of scientific evidence; and
     General scientific principles in conducting comparative 
structural analyses, functional assays, animal testing, human PK and PD 
studies, clinical immunogenicity assessment, and comparative clinical 
trials (including clinical study design issues).
    In the Federal Register of February 15, 2012 (77 FR 8883), FDA 
announced the availability of the draft guidance of the same title 
dated February 2012. FDA received a number of comments on the draft 
guidance. In response to these comments, FDA provides further 
clarification of the scientific considerations applicable to the 
conduct of comparative structural analysis, functional assays, animal 
studies, and clinical testing. The final guidance also provides 
additional information on clinical trial design and selection of study 
endpoint and population. It also explains FDA's current thinking on 
when a comparative clinical trial may not be needed. In addition, 
editorial changes were made to improve clarity. The guidance announced 
in this notice finalizes and replaces the draft guidance dated 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 scientific considerations in demonstrating 
biosimilarity 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 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 describes information collection provisions that are 
subject to review by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520). 
This guidance references information collections that are already 
approved by OMB and are not expected to change as a result of the 
guidance. This includes information collections related to the 
submission of: (1) An investigational new drug application, which is 
covered under 21 CFR part 312 and approved under OMB Control No. 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 under section 351(a) of the PHS Act, which is 
covered under 21 CFR part 601 and approved under OMB control number 
0910-0338; and (4) a biologics license application under section 351(k) 
of the PHS Act, which is covered under 21 CFR 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. 2015-10062 Filed 4-29-15; 8:45 am]
BILLING CODE 4164-01-P


