[Federal Register Volume 82, Number 11 (Wednesday, January 18, 2017)]
[Notices]
[Pages 5579-5580]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-01042]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-D-0154]


Considerations in Demonstrating Interchangeability With a 
Reference Product; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled 
``Considerations in Demonstrating Interchangeability With a Reference 
Product.'' This guidance is intended to assist sponsors in 
demonstrating that a proposed therapeutic protein product (proposed 
interchangeable product or proposed product) is interchangeable with a 
reference product for the purposes of submitting a marketing 
application or supplement under the Public Health Service Act (PHS 
Act). This guidance is one in a series of guidances that FDA has 
developed to implement the Biologics Price Competition and Innovation 
Act of 2009 (BPCI Act).

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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by March 20, 2017.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2017-D-0154 for ``Considerations in Demonstrating 
Interchangeability With a Reference Product; Draft Guidance for 
Industry; Availability.'' Received comments will be placed in the 
docket and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at https://www.regulations.gov or at the Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    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, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; or to the 
Office of Communication, Outreach and Development, 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.

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 draft guidance for industry 
entitled ``Considerations in Demonstrating Interchangeability With a 
Reference Product.'' This guidance is intended to assist sponsors in 
demonstrating that a proposed therapeutic protein product (proposed 
interchangeable product or proposed product) is interchangeable with a 
reference product for the purposes of submitting a marketing 
application or supplement under section 351(k) of the PHS Act (42 
U.S.C. 262(k)). The BPCI Act amends the PHS Act and other statutes to 
create an

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abbreviated licensure pathway in section 351(k) 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 Of 2010 (Affordable Care 
Act) (Pub. L. 111-148)).
    Section 351(k) of the PHS Act sets forth the requirements for an 
application for a proposed biosimilar product and an application or a 
supplement for a proposed interchangeable product. Specifically, 
section 351(k)(4) provides that upon review of an application submitted 
under section 351(k), or any supplement to such an application, FDA 
will determine the biological product to be interchangeable with the 
reference product if FDA determines that the information submitted in 
the application (or supplement) is sufficient to show that the 
biological product is biosimilar to the reference product and can be 
expected to produce the same clinical result as the reference product 
in any given patient; and for a biological product that is administered 
more than once to an individual, the risk in terms of safety or 
diminished efficacy of alternating or switching between use of the 
biological product and the reference product is not greater than the 
risk of using the reference product without such alternation or switch. 
Section 351(i) of the PHS Act states that the term interchangeable or 
interchangeability, in reference to a biological product that is shown 
to meet the standards described in subsection 351(k)(4), means that the 
biological product may be substituted for the reference product without 
the intervention of the health care provider who prescribed the 
reference product.
    This guidance gives an overview of important scientific 
considerations in demonstrating interchangeability, including:
     The data and information needed to support a demonstration 
of interchangeability;
     Considerations for the design and analysis of a switching 
study or studies to support a demonstration of interchangeability;
     Recommendations regarding the use of U.S.-licensed 
reference products in a switching study or studies; and
     Considerations for developing presentations, container 
closure systems, and delivery device constituent parts for proposed 
interchangeable products.
    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 current thinking of FDA on topics 
sponsors should consider when seeking to demonstrate that a proposed 
therapeutic protein product is interchangeable with a reference 
product. It does not establish any rights for any person and is not 
binding on FDA or the public.

II. Topics for Comment

    In addition to comment on the draft guidance, we also invite 
general comments on interchangeability, including comments on 
regulation of an interchangeable product over its lifecycle, as well as 
comments on the following topics:
    1. Since the mid-1990s, FDA has approved manufacturing changes for 
biological products based on data from comparability assessments 
comparing the pre-change and post-change product using comparative 
analytical, and, when necessary, animal and/or clinical (e.g., 
pharmacokinetic, immunogenicity) studies. A demonstration of 
comparability between pre- and post-change product supports a 
determination that the safety and efficacy profile remains the same for 
the product. With respect to interchangeable products, are there 
considerations in addition to comparability assessments that FDA should 
consider in regulating post-approval manufacturing changes of 
interchangeable products? Your comments should include the scientific 
rationale and justification for your recommendations, as well as 
recommendations for processes and systems (including key logistics) to 
implement your recommendations.
    2. As explained in the guidance ``Considerations in Demonstrating 
Interchangeability With a Reference Product,'' FDA expects that 
sponsors seeking an interchangeability determination will submit data 
and information to support a showing that the proposed interchangeable 
product can be expected to produce the same clinical result as the 
reference product in all of the reference product's licensed conditions 
of use. How, if at all, should the Agency consider conditions of use 
that are licensed for the reference product after an interchangeable 
product has been licensed? Your comments should include the scientific 
rationale and justification for your recommendations, as well as 
recommendations for processes and systems (including key logistics) to 
implement your recommendations.

III. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. 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 under 21 CFR part 312 have been approved 
under OMB control number 0910-0014; the collections of information 
under 21 CFR part 601 have been approved under OMB control number 0910-
0338; and the collections of information under section 351(k) of the 
PHS Act have been approved under OMB control number 0910-0719.

IV. Electronic Access

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

    Dated: January 12, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-01042 Filed 1-17-17; 8:45 am]
 BILLING CODE 4164-01-P