[Federal Register Volume 84, Number 99 (Wednesday, May 22, 2019)]
[Notices]
[Pages 23569-23571]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-10667]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-2102]


Development of Therapeutic Protein Biosimilars: Comparative 
Analytical Assessment and Other Quality-Related Considerations; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled 
``Development of Therapeutic Protein Biosimilars: Comparative 
Analytical Assessment and Other Quality-Related Considerations.'' This 
draft guidance describes the Agency's recommendations on the design and 
evaluation of comparative analytical studies intended to support a 
demonstration that a proposed therapeutic protein product is biosimilar 
to a reference product licensed under the Public Health Service Act 
(PHS Act). Additionally, this draft guidance is intended to provide 
recommendations to sponsors on the scientific and technical information 
for the chemistry, manufacturing, and controls (CMC) portion of a 
marketing application for a proposed product submitted under the PHS 
Act. This draft guidance revises the guidance entitled ``Quality 
Considerations in Demonstrating Biosimilarity of a Therapeutic Protein 
Product to a Reference Product'' that was published on April 30, 2015.

DATES: Submit either electronic or written comments on the draft 
guidance by July 22, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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

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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-2019-D-2102 for ``Development of Therapeutic Protein Biosimilars: 
Comparative Analytical Assessment and Other Quality-Related 
Considerations.'' 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 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. 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 draft guidance for industry 
entitled ``Development of Therapeutic Protein Biosimilars: Comparative 
Analytical Assessment and Other Quality-Related Considerations.'' This 
draft guidance describes the Agency's recommendations on the design and 
evaluation of comparative analytical studies intended to support a 
demonstration that a proposed therapeutic protein product is biosimilar 
to a reference product licensed under section 351(a) of the PHS Act (42 
U.S.C. 262(a)). Additionally, this draft guidance is intended to 
provide recommendations to sponsors on of the scientific and technical 
information for the CMC portion of a marketing application for a 
proposed product submitted under section 351(k) of the PHS Act. 
Although the 351(k) pathway applies generally to biological products, 
this guidance focuses on therapeutic protein products.
    The Biologics Price Competition and Innovation Act of 2009 was 
enacted as part of the Patient Protection and Affordable Care Act (Pub. 
L. 111-148) on March 23, 2010, and 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, among other things, FDA determines that the information 
submitted in the application is sufficient to show that the biological 
product is biosimilar to the reference product.
    In the Federal Register of February 15, 2012 (77 FR 8884), FDA 
announced the availability of the draft guidance entitled ``Quality 
Considerations in Demonstrating Biosimilarity to a Reference Protein 
Product.'' FDA received a number of comments on the draft guidance. In 
response to these comments, FDA provided further clarification on the 
general principles described through a final guidance entitled 
``Quality Considerations in Demonstrating Biosimilarity of a 
Therapeutic Protein Product to a Reference Product,'' which was 
announced in the Federal Register of April 30, 2015 (80 FR 24257).
    In the Federal Register of September 22, 2017 (82 FR 44425), FDA 
announced the availability of the draft guidance entitled ``Statistical 
Approaches to Evaluate Analytical Similarity.'' FDA received a number 
of comments on the draft guidance. Comments submitted to the docket 
addressed a range of issues that could impact the cost and efficiency 
of biosimilar development, including the number of reference product 
lots the draft guidance would have recommended that biosimilar 
developers sample in their evaluation of high similarity and the 
statistical methods for this evaluation. After considering the public 
comments that FDA received, FDA determined it would withdraw the draft 
guidance to give further consideration to the scientific and regulatory 
issues involved. FDA announced the withdrawal of the draft

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guidance on June 21, 2018, with the intention of issuing future draft 
guidance on the evaluation of analytical data to support a 
demonstration that a proposed biosimilar product is highly similar to a 
reference product.
    This draft guidance revises the guidance issued on April 30, 2015. 
FDA has adjusted the title of this draft guidance to more clearly 
communicate that this draft guidance includes the Agency's 
recommendations on the design and evaluation of comparative analytical 
studies intended to support a demonstration that a proposed therapeutic 
protein product is biosimilar to a reference product. In addition to 
editorial and clarifying edits, the draft guidance includes a section 
that fulfills the Biosimilar User Fee Act II commitment to publish a 
revised draft or final guidance, describing statistical considerations 
for the analysis of analytical similarity data intended to support a 
demonstration of ``highly similar'' for biosimilar biological products 
within 18 months after the close of the public comment period for the 
withdrawn guidance, ``Statistical Approaches to Evaluate Analytical 
Similarity.''
    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 ``Development 
of Therapeutic Protein Biosimilars: Comparative Analytical Assessment 
and Other Quality-Related Considerations.'' 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, which are not expected to change 
as a result of the guidance. 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 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 
(BLA) under section 351(a) of the PHS Act, which is covered under part 
601 (21 CFR part 601) and approved under OMB control number 0910-0338; 
and (4) a BLA under section 351(k), which is covered under part 601 and 
approved under OMB control number 0910-0719.

III. Electronic Access

    Persons with access to the internet may obtain the draft 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 16, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-10667 Filed 5-21-19; 8:45 am]
 BILLING CODE 4164-01-P