
[Federal Register Volume 79, Number 150 (Tuesday, August 5, 2014)]
[Notices]
[Pages 45448-45450]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-18169]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-D-1165]


Draft Guidance for Industry on Reference Product Exclusivity for 
Biological Products Filed Under Section 351(a) of the Public Health 
Service Act; 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availability of a draft guidance for industry entitled ``Reference 
Product Exclusivity for Biological Products Filed Under Section 351(a) 
of the PHS Act.'' This draft guidance is intended to assist sponsors 
developing biological products, sponsors holding biologics license 
applications (BLAs), and other interested parties in providing 
information and data that will help the Agency determine the date of 
first licensure for a reference product under 351(k)(7)(C) of the 
Public Health Service Act (PHS Act), as added by the Biologics Price 
Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act amends 
the PHS Act and other statutes to create an abbreviated licensure 
pathway for biological products shown to be biosimilar to, or 
interchangeable with, an FDA-licensed biological reference product.

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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by October 6, 2014. Submit either electronic or written 
comments concerning the proposed collection of information by October 
6, 2014.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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 
Office of Communication, Outreach and Development (HFM-40), Center for 
Biologics Evaluation and Research, 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 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, 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 draft guidance for industry 
entitled ``Reference Product Exclusivity for Biological Products Filed 
Under Section 351(a) of the PHS Act.'' This draft guidance is intended 
to assist sponsors who are developing biological products, sponsors of 
BLAs, and other interested parties in providing information that will 
help the Agency determine the date of first licensure for a reference 
product under 351(k)(7)(C) of the Public Health Service Act (PHS Act) 
as added by the Biologics Price Competition and Innovation Act of 2009 
(BPCI Act).
    The BPCI Act amends the PHS Act and other statutes to create an 
abbreviated licensure pathway for biological products shown to be 
biosimilar to, or interchangeable with, an FDA-licensed biological 
reference product (see sections 7001 through 7003 of the Patient 
Protection and Affordable Care Act (Pub. L. 111-148)). Section 
351(k)(7) of the PHS Act, entitled ``Exclusivity for Reference 
Product,'' describes reference product exclusivity, the period of time 
in which a 351(k) sponsor is not permitted to submit and FDA is not 
permitted to license a 351(k) application that references a reference 
product, the single biological product licensed under section 351(a) of 
the PHS Act against which a biological product is evaluated in a 351(k) 
application. Under this section, exclusivity for the reference product 
is described in terms

[[Page 45449]]

of a prohibition on acceptance or approval of an application for a 
biosimilar or interchangeable product for a period of time starting 
from the date of first licensure. Specifically, approval of a 351(k) 
application may not be made effective until 12 years after the date of 
first licensure of the reference product which under the statute 
excludes the date of licensure of supplements and certain other 
applications. A 351(k) application for a biosimilar or interchangeable 
biological product cannot be submitted for review until 4 years after 
the date on which the reference product was first licensed under 
section 351(a) of the PHS Act.
    Determining the date of first licensure for a reference product, in 
turn, determines whether a particular biological product qualifies for 
a period of exclusivity under 351(k)(7) of the PHS Act and the date on 
which such exclusivity, if any, will expire. Making this determination 
can present unique challenges given the requirements of section 
351(k)(7) of the PHS Act. These are made more acute because of the 
scientific and technical complexities that may be associated with the 
larger and typically more complex structures of biological products as 
compared with small molecule drugs, as well as the processes by which 
such biological products are made. Therefore, the 351(a) applicant may 
provide information to FDA, such as that described in this guidance or 
other relevant information, to assist FDA with its analysis of the date 
of first licensure for a biological product under section 351(k)(7) of 
the PHS Act.
    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 determining 
the date of first licensure for biological products filed under section 
351(a) of the PHS Act. 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. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal Agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information they 
conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 
60-day notice in the Federal Register concerning each proposed 
collection of information before submitting the collection to OMB for 
approval. To comply with this requirement, FDA is publishing notice of 
the proposed collection of information set forth in this document.
    This draft guidance also refers to previously approved collections 
of information found in FDA regulations. The collections of information 
in 21 CFR 314.50 and 21 CFR part 601 (BLA) have been approved under OMB 
control numbers 0910-0001 and 0910-0338, respectively. The general 
licensing provisions under section 351(k) (biosimilar applications) of 
the BPCI Act have been approved under OMB control number 0910-0719.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Draft Guidance for Industry on Reference Product Exclusivity 
for Biological Products Filed Under Section 351(a) of the PHS Act.
    Description of Respondents: Respondents to the proposed collection 
of information include sponsors developing biological products and 
sponsors holding BLAs.
    Burden Estimate: The draft guidance proposes a new collection of 
information by requesting information and data from sponsors to assist 
FDA in determining the date of first licensure for a reference product 
filed under section 351(a) of the PHS Act described under section 
351(k)(7) of the PHS Act as added by the BPCI Act. The proposed 
collection of information includes information that would describe and 
explain how a proposed product is structurally the same as or different 
from any previously licensed biological product, along with supporting 
information that describes how such modification results in a change in 
safety, purity, or potency of the product. FDA recommends that the 
sponsor include information as described in the draft guidance at the 
time the 351(a) application is submitted or, in the case of a 
previously approved 351(a) application, as a supplement to the 
application. Alternatively, this information may be submitted as an 
amendment to the 351(a) application. A summary of the recommended 
information includes the following: (1) A list of all licensed 
biological products that are structurally related to the biological 
product that is the subject of the 351(a) application being considered; 
(2) of those licensed biological products identified in item 1, the 
identification of the products for which the sponsor or one of the 
sponsor's affiliates, including any licensors, predecessors in 
interest, successors in interest, or related entities, are the current 
or previous license holder; (3) description of the structural 
differences between the proposed product and any products identified in 
item 2; and (4) description of the change in safety, purity, and/or 
potency between the proposed product and any products identified in 
item 2. The proposed collection of information also includes any other 
information and data that would assist FDA in making a determination of 
the date of first licensure for biological products and BLAs as 
described under section 351(k)(7) of the PHS Act. FDA estimates the 
burden of this collection of information as follows:

[[Page 45450]]



                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                       Number of                         Average
        Reporting activity            Number of      responses per     Total annual    burden per    Total hours
                                     respondents       respondent       responses       response
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Information for Determination of               10                1               10           150         1,500
 the Date of First Licensure.....
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    As indicated in table 1 of this document, FDA estimates that it 
will receive a total of approximately 10 requests annually for 
determination of the date of first licensure of a 351(a) product under 
351(k)(7) of the PHS Act. The average burden per response (hours) is 
based on FDA experience with similar information collection 
requirements.

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: July 29, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-18169 Filed 8-4-14; 8:45 am]
BILLING CODE 4164-01-P


