[Federal Register Volume 77, Number 31 (Wednesday, February 15, 2012)]
[Notices]
[Pages 8883-8884]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-3552]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Draft Guidance for Industry on Scientific Considerations in 
Demonstrating Biosimilarity 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availability of a draft guidance for industry entitled ``Scientific 
Considerations in Demonstrating Biosimilarity to a Reference Product.'' 
This draft guidance is intended to assist sponsors in demonstrating 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 This draft guidance gives an 
overview of FDA's approach to determining biosimilarity.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by April 16, 2012.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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, Food and Drug Administration, 
1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov.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 (HFM-17), Food and Drug Administration, 1401 Rockville Pike, 
Suite 200N, Rockville, MD 20852-1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Scientific Considerations in Demonstrating Biosimilarity to 
a Reference Product.'' This draft 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), Public Law 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, 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 draft 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 draft 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 therapeutic protein product 
and the reference product with respect to structure, function, animal 
toxicity, human pharmacokinetics and pharmacodynamics, clinical 
immunogenicity, and clinical safety and effectiveness;
     The totality-of-the-evidence approach that FDA will use to 
review applications for biosimilar products; and
     General scientific principles in conducting comparative 
structural and functional analysis, animal testing, human 
pharmacokinetics and pharmacodynamics studies, clinical immunogenicity 
assessment, and clinical safety and effectiveness studies (including 
clinical study design issues).
    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 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

[[Page 8884]]

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 to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. 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.

III. The Paperwork Reduction Act

    This draft 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). In particular, the draft guidance refers to information 
collections related to the submission of 351(k) application. In 
accordance with the PRA, FDA is soliciting public comment, in a 
separate document published elsewhere in this issue of the Federal 
Register (see ``Agency Information Collection Activities: Proposed 
Collection; Comment Request; General Licensing Provisions; Section 
351(k) Biosimilar Applications'') on the information collection 
associated with the submission of a 351(k) application. FDA will also 
seek OMB approval for this information collection.
    In addition, this draft guidance references other information 
collections that are already approved by OMB and are not expected to 
change as a result of the draft 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 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, which is covered under 
21 CFR part 601 and approved under OMB control number 0910-0338; and 
(4) labeling, which is covered under 21 CFR 201.57 and approved under 
OMB control number 0910-0572.

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: February 9, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-3552 Filed 2-14-12; 8:45 am]
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