[Federal Register Volume 84, Number 93 (Tuesday, May 14, 2019)]
[Notices]
[Pages 21342-21344]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-10001]


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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; 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 final guidance for industry entitled 
``Considerations in Demonstrating Interchangeability With a Reference 
Product.'' This guidance is intended to

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assist sponsors in demonstrating that a proposed therapeutic protein 
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: The guidance was posted to the Agency's website on May 10, 2019.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time 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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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.'' 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 Dockets Management Staff 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 Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    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, 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 guidance document.

FOR FURTHER INFORMATION CONTACT: Sandra Benton, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 6522, 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 ``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) 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)).
    Section 351(k) of the PHS Act sets forth the requirements for an 
application for a proposed biosimilar product and for 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 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

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biological product that is shown to meet the standards described in 
section 351(k)(4), means that the biological product may be substituted 
for the reference product without the intervention of the healthcare 
provider who prescribed the reference product.
    This guidance gives an overview of important scientific 
considerations in demonstrating interchangeability with a reference 
product, including:
     The data and information recommended to support a 
demonstration of interchangeability
     Considerations for the design and analysis of a switching 
study or studies to support a demonstration of interchangeability
     Considerations regarding the comparator product in a 
switching study or studies
     Abbreviated considerations for developing presentations, 
container closure systems, and delivery device constituent parts for 
proposed interchangeable products
    This guidance finalizes the draft guidance issued on January 18, 
2017. Changes made to the guidance took into consideration the comments 
received. FDA provided changes to clarify its recommendations for 
demonstrating interchangeability with the reference product. FDA 
intends to provide more detailed recommendations on the data and 
information recommended to support the proposed interchangeable 
product's presentation and related issues in a separate guidance.
    In the Federal Register of January 18, 2017 (82 FR 5579), FDA 
announced the availability of the draft guidance for industry 
``Considerations in Demonstrating Interchangeability With a Reference 
Product.'' FDA requested comment on the following questions: (1) Are 
there considerations in addition to comparability assessments that FDA 
should consider in regulating post-approval manufacturing changes of 
interchangeable products and (2) 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. The comments 
submitted in response to these questions are being considered; FDA will 
address these topics in future guidance, as appropriate.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Considerations in Demonstrating 
Interchangeability With a Reference Product.'' It does not establish 
any rights for any person and is not binding on FDA or the public. You 
can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations. This guidance is not subject to 
Executive Order 12866.

II. Paperwork Reduction Act of 1995

    This 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.

III. Electronic Access

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

    Dated: May 10, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-10001 Filed 5-10-19; 11:15 am]
 BILLING CODE 4164-01-P