[Federal Register Volume 85, Number 44 (Thursday, March 5, 2020)]
[Notices]
[Pages 12930-12932]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-04537]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-4750]


The ``Deemed To Be a License'' Provision of the Biologics Price 
Competition and Innovation Act: Questions and Answers; Guidance for 
Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled ``The 
`Deemed To Be a License' Provision of the BPCI Act: Questions and 
Answers.'' This guidance is intended to provide answers to common 
questions about FDA's implementation of the statutory provision under 
which an application for a biological product approved under the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) as of March 23, 2020, 
will be deemed to be a license for the biological product under the 
Public Health Service Act (PHS Act) on March 23, 2020. This guidance 
also describes FDA's compliance policy for the labeling of biological 
products that will be the subject of deemed biologics license 
applications (BLAs). This guidance is intended to facilitate planning 
for the March 23, 2020, transition date and provide further clarity 
regarding the Agency's implementation of this statutory provision. This 
guidance finalizes the draft guidance of the same title issued on 
December 12, 2018.

DATES: The announcement of the guidance is published in the Federal 
Register on March 5, 2020.

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-2015-D-4750 for ``The `Deemed To Be a License' Provision of the 
BPCI Act: Questions and Answers.'' 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

[[Page 12931]]

``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.govinfo.gov/content/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. 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: Janice Weiner, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6270, Silver Spring, MD 20993-0002, 301-
796-3475, Janice.Weiner@fda.hhs.gov; or Stephen Ripley, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7268, Silver Spring, MD 20993-0002, 
240-402-7911, Stephen.Ripley@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``The `Deemed to be a License' Provision of the BPCI Act: 
Questions and Answers.'' This guidance is intended to provide answers 
to common questions about FDA's implementation of the ``transition'' 
provision of the Biologics Price Competition and Innovation Act of 2009 
(BPCI Act) under which an application for a biological product approved 
under section 505 of the FD&C Act (21 U.S.C. 355) as of March 23, 2020, 
will be deemed to be a license for the biological product under section 
351 of the PHS Act (42 U.S.C. 262) on March 23, 2020 (``the transition 
date''). This guidance also describes FDA's compliance policy for the 
labeling of biological products that will be the subject of deemed 
BLAs. This guidance is intended to facilitate planning for the 
transition date and provide further clarity regarding the Agency's 
implementation of this statutory provision.
    Although the majority of therapeutic biological products have been 
licensed under section 351 of the PHS Act, some protein products 
historically have been approved under section 505 of the FD&C Act. On 
March 23, 2010, the BPCI Act was enacted as part of the Patient 
Protection and Affordable Care Act (Pub. L. 111-148). The BPCI Act 
clarified the statutory authority under which certain protein products 
will be regulated by amending the definition of a ``biological 
product'' in section 351(i) of the PHS Act to include a ``protein 
(except any chemically synthesized polypeptide),'' and describing 
procedures for submission of a marketing application for certain 
``biological products.'' Section 605 of the Further Consolidated 
Appropriations Act, 2020 (Pub. L. 116-94), further amended the 
definition of a ``biological product'' in section 351(i) of the PHS Act 
to remove the parenthetical ``(except any chemically synthesized 
polypeptide)'' from the statutory category of ``protein.'' In the 
Federal Register of February 21, 2020, FDA issued a final rule that 
amends its regulation that defines ``biological product'' to 
incorporate changes made by the BPCI Act and the Further Consolidated 
Appropriations Act, 2020, and to provide its interpretation of the 
statutory term ``protein'' (85 FR 10057). This rule is effective on 
March 23, 2020. FDA also has previously stated its interpretation of 
the statutory term ``protein'' in the amended definition of 
``biological product'' (see FDA's draft guidance for industry entitled 
``New and Revised Draft Q&As on Biosimilar Development and the BPCI Act 
(Revision 2)'' (December 2018), available on FDA's website at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs (``Biosimilar Q&A Draft Guidance'')).\1\
---------------------------------------------------------------------------

    \1\ FDA also described its interpretation of the statutory term 
``chemically synthesized polypeptide'' in the Biosimilar Q&A Draft 
Guidance and the proposed rule entitled ``Definition of the Term 
`Biological Product' '' (83 FR 63817, December 12, 2018); however, 
this interpretation is no longer necessary to our interpretation of 
the statutory term ``biological product'' in light of the amendment 
made by section 605 of the Further Consolidated Appropriations Act, 
2020.
---------------------------------------------------------------------------

    The BPCI Act requires that a marketing application for a 
``biological product'' (that previously could have been submitted under 
section 505 of the FD&C Act) must be submitted under section 351 of the 
PHS Act; this requirement is subject to certain exceptions during a 10-
year transition period ending on March 23, 2020 (see section 7002(e)(1) 
to (3) and (e)(5) of the BPCI Act). On March 23, 2020, an approved 
application for a biological product under section 505 of the FD&C Act 
shall be deemed to be a license for the biological product under 
section 351 of the PHS Act (see section 7002(e)(4) of the BPCI Act).\2\
---------------------------------------------------------------------------

    \2\ Section 607 of the Further Consolidated Appropriations Act, 
2020, amended section 7002(e)(4) of the BPCI Act to provide that FDA 
will continue to review an application for a biological product 
under section 505 of the FD&C Act after March 23, 2020, so long as 
that application was submitted under section 505 of the FD&C Act, is 
filed not later than March 23, 2019, and is not approved as of March 
23, 2020. If such an application is approved under section 505 of 
the FD&C Act before October 1, 2022, it will be deemed to be a 
license for the biological product under section 351 of the PHS Act 
upon approval (see section 7002(e)(4)(B)(iii) and (vi) of the BPCI 
Act).
---------------------------------------------------------------------------

    In the Federal Register of December 12, 2018 (83 FR 63894), FDA 
invited comment on the preliminary list of approved applications for 
biological products under the FD&C Act that will be affected by the 
transition provision (``Preliminary List'') (available on FDA's website 
at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/deemed-be-license-provision-bpci-act). FDA explained that 
if an application holder or other person believes that an approved new 
drug application (NDA) should be added to the list or should not be 
included on the list, the application holder or other person should 
submit a comment to the public docket established for this Q&A guidance 
and the list. FDA posted updates to the Preliminary List on September 
23, 2019, and January 15, 2020.
    In the Federal Register of December 12, 2018, FDA also invited 
comment on the factors that FDA should consider in determining whether 
a combination product composed of a biological product constituent part 
and a drug constituent part will be subject to the transition 
provision. However, FDA did not receive any substantive comments on 
this topic. The current Preliminary List includes a small number of 
drug-biologic combination products and complex mixtures assigned to the 
Center for Drug Evaluation and Research, which reflects the Agency's 
current thinking that the approved NDAs for these products are 
appropriately subject

[[Page 12932]]

to the transition provision. FDA's evaluation of each of these approved 
NDAs for drug-biologic combination products or complex mixtures was 
informed by a general consideration of the factors used to determine 
the appropriate marketing application type for antibody-drug conjugates 
(see FDA's guidance for industry entitled ``Questions and Answers on 
Biosimilar Development and the BPCI Act'' (December 2018), available on 
FDA's website at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs).
    To ensure that the Agency considers any additional comments on the 
list before the statutory transition date, the January 2020 update to 
the Preliminary List recommended that application holders or other 
interested persons submit either electronic or written comments no 
later than February 19, 2020.
    This guidance finalizes the draft guidance entitled ``The `Deemed 
to be a License' Provision of the BPCI Act: Questions and Answers'' 
issued on December 12, 2018 (83 FR 63894). FDA considered comments 
received on the draft guidance as the guidance was finalized. Changes 
from the draft to the final guidance include: (1) Providing information 
on updating the listing information for the biological product in FDA's 
electronic Drug Registration and Listing System between March 23, 2020, 
and June 30, 2020; (2) clarifying that, in the absence of other changes 
made by the application holder that would require a new National Drug 
Code (NDC) number, biological products approved under the FD&C Act will 
retain their current NDC number after the NDA is deemed to be a BLA; 
(3) providing information on establishment standards for ``non-
specified biological products'' that are the subject of deemed BLAs; 
(4) clarifying the process for submitting followup reports on or after 
March 23, 2020, for any initial field alert report submitted before 
March 23, 2020; and (5) clarifying certain aspects of FDA's compliance 
policy for the labeling of biological products that are the subject of 
deemed BLAs. In addition, technical changes were made for consistency 
with the revisions to the PHS Act and the BPCI Act enacted in sections 
605 and 607 of the Further Consolidated Appropriations Act, 2020, and 
editorial changes were made to improve clarity.
    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 ``The `Deemed To Be a License' Provision of 
the BPCI Act: Questions and Answers.'' 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.

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. 3501-3521). The 
collections of information in 21 CFR part 314 have been approved under 
0910-0001; the collections of information in 21 CFR parts 601 and 610 
have been approved under 0910-0338; the collections of information in 
21 CFR 600.80 through 600.90 have been approved under 0910-0308; and 
the collections of information in 21 CFR 201.56, 201.57, and 201.80 
have been approved under 0910-0572. In addition, the collections of 
information for applications submitted under section 351(k) of the PHS 
Act have been approved under 0910-0719.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs or https://www.regulations.gov.

    Dated: March 2, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-04537 Filed 3-4-20; 8:45 am]
 BILLING CODE 4164-01-P


