[Federal Register Volume 83, Number 143 (Wednesday, July 25, 2018)]
[Proposed Rules]
[Pages 35154-35157]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-15859]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 15

[Docket No. FDA-2018-N-2689]


Facilitating Competition and Innovation in the Biological 
Products Marketplace; Public Hearing; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing a public hearing on FDA's approach to enhancing competition 
and innovation in the biological products marketplace, including by 
facilitating greater availability of biosimilar and interchangeable 
products.

DATES: The public hearing will be held on Tuesday, September 4, 2018, 
from 9 a.m. to 5 p.m. The public hearing may be extended or may end 
early, depending on the level of public participation. Persons seeking 
to attend or to present at the public hearing must register by Tuesday, 
August 14, 2018. Section III provides attendance and registration 
information. Electronic or written comments will be accepted after the 
public hearing until Friday, September 21, 2018.

ADDRESSES: The public hearing will be held at the FDA White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room 
(Rm. 1503A), Silver Spring, MD 20993-0002. Entrance for public hearing 
participants (non-FDA employees) is through Building 1, where routine 
security check procedures will be performed. For parking and security 
information, please refer to https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    You may submit comments as follows. Please note that late, untimely 
filed comments will not be considered. Electronic comments must be 
submitted on or before Friday, September 21, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of Friday, September 21, 2018. 
Comments received by mail/hand delivery/courier (for written/paper 
submissions) will be considered timely if they are postmarked or the 
delivery service acceptance receipt is on or before that date.

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-2018-N-2689 for ``Facilitating Competition and Innovation in the 
Biological Products Marketplace; Public Hearing; Request for 
Comments.'' Received comments, those filed in a timely manner (see 
ADDRESSES), 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

[[Page 35155]]

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.

FOR FURTHER INFORMATION CONTACT: Allison Hoffman, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 1, Rm. 1314, Silver 
Spring, MD 20993, 301-796-9203, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    The Biologics Price Competition and Innovation Act of 2009 (BPCI 
Act) amended the Public Health Service Act (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. The BPCI Act was intended to balance 
innovation and consumer interests. The abbreviated licensure pathway, 
in section 351(k) of the PHS Act, allows an applicant (a ``351(k) 
applicant'') to rely, in part, on FDA's previous determination of 
safety and effectiveness for the reference product for approval. The 
BPCI Act provides, among other things, exclusivity periods for certain 
biological products licensed in ``stand alone'' applications under 
section 351(a) of the PHS Act.
    As the marketplace of biological products continues to expand and 
evolve, FDA expects that increased availability of biosimilars and 
interchangeable products will result in more competition and create 
savings for patients and the healthcare system. At the same time, we 
recognize that there are challenges to the rapid growth of this 
marketplace. For instance, although FDA has approved 11 marketing 
applications for biosimilars as of July 1, 2018, FDA is aware that the 
majority of biosimilars licensed by FDA have not yet been marketed and 
are not available to patients.
    Although such delays in the market entry of an approved biosimilar 
are outside FDA's control, we remain focused on FDA's critical role in 
increasing the availability of biosimilars and interchangeable 
products. Recognizing that this is a crucial time in the emergence of 
the marketplace of biosimilar and interchangeable products, FDA 
recently developed a Biosimilars Action Plan. This Plan focuses on four 
key areas: (1) Improving the efficiency of the biosimilar and 
interchangeable product development and approval process; (2) 
maximizing scientific and regulatory clarity for the biosimilar product 
development community; (3) developing effective communications to 
improve understanding of biosimilars among patients, clinicians, and 
payors; and (4) supporting market competition by reducing gaming of FDA 
requirements or other attempts to unfairly delay competition.
    FDA's Biosimilars Action Plan builds on the Agency's substantial 
progress, to date, implementing the approval pathway for biosimilar and 
interchangeable products. For example, FDA has issued guidance for 
industry on numerous scientific and regulatory issues related to the 
development of proposed biosimilar and interchangeable products. FDA 
also created the Biosimilar Product Development (BPD) Program to 
facilitate the rapid development of biosimilar and interchangeable 
products. Through enrollment in this program, FDA provides detailed, 
product-specific advice to manufacturers. As of July 1, 2018, 68 
programs were enrolled in the BPD Program and FDA had received meeting 
requests to discuss the development of biosimilars for 31 different 
reference products.
    FDA has also prioritized its efforts to provide useful information 
about licensed biological products to the public. FDA publishes the 
Purple Book: Lists of Licensed Biological Products with Reference 
Product Exclusivity and Biosimilarity or Interchangeability Evaluations 
\1\ to provide information on licensed biological products, including 
information on exclusivity for reference products and on whether a 
product has been demonstrated to be biosimilar to, or interchangeable 
with, a reference product. Another FDA priority is the development of 
educational materials for patients, healthcare providers, and other 
stakeholders to increase knowledge about biological products, including 
biosimilar and interchangeable products. For example, FDA launched an 
educational campaign in October 2017 to promote understanding by 
healthcare providers of biosimilar and interchangeable products and how 
these products can help patients (see, https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580435.htm).
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    \1\https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm411418.htm.
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    As FDA continues working to implement the BPCI Act, FDA welcomes 
input from the public on how the Agency can enhance its efforts to 
increase access by patients to state-of-the-art, lifesaving treatment 
options by encouraging innovation and competition in the biological 
products marketplace. FDA will hold a public hearing on September 4, 
2018, from 9 a.m. to 5 p.m., to provide an opportunity for all 
interested stakeholders to submit comments.
    The format of the hearing involves presentations from the public. 
The Agency will not be inviting specific presenters; rather, with this 
document, FDA is soliciting presentations from interested stakeholders. 
FDA also invites interested persons to submit written comments to the 
docket on the topics described in section II.

II. Purpose and Scope of the Public Hearing

    FDA is soliciting input from the public on how to facilitate 
greater availability of biosimilar and interchangeable products while 
retaining the balance between competition and innovation that Congress 
intended to achieve under the BPCI Act. FDA is holding a public hearing 
to receive information and comments from a broad group of stakeholders, 
including patients,

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researchers, healthcare providers, manufacturers, interested industry, 
professional organizations, and the public. The Agency has determined 
that a public hearing is the most appropriate way to ensure public 
engagement.
    FDA welcomes any relevant information that stakeholders wish to 
share. FDA is particularly interested in stakeholder input on how the 
Agency can achieve the following goals:
     Facilitate the efficient development of biosimilar and 
interchangeable products using state-of-the-art science;
     Develop information resources, as well as scientific or 
regulatory tools, to streamline the development of biosimilar and 
interchangeable products;
     Enhance the efficiency of FDA review of marketing 
applications for biosimilar and interchangeable products;
     Provide additional scientific or regulatory clarity 
regarding FDA's regulation of biological products, including FDA's 
review and approval of marketing applications for biological products;
     Increase healthcare provider, patient, and payor 
understanding of biological products, including biosimilar and 
interchangeable products; and
     Support market competition by addressing attempts to game 
FDA requirements or otherwise delay market entry of competing 
biological products.
    FDA is also interested in stakeholder input on the following 
questions about additional steps FDA can take, within its statutory 
authority, related to the Agency's regulation of biological products:
    1. FDA is aware that many of the biosimilar products that have been 
licensed by FDA are not yet marketed and available to patients. What 
can FDA do to help biosimilars and interchangeable products reach 
patients more quickly after these products are licensed?
    2. FDA uses the Purple Book to provide information about biological 
products licensed under section 351 of the PHS Act. What additional 
information or features could be incorporated into the Purple Book to 
make it more useful to stakeholders, including patients, healthcare 
providers, pharmacists, and manufacturers?
    3. FDA expects that the number of licensed biosimilar and 
interchangeable products will continue to increase in the coming years. 
In many, if not most, cases, FDA anticipates that multiple products 
will be licensed as biosimilar to, or interchangeable with, a given 
reference product. What additional steps can FDA take to facilitate the 
evolution of the biosimilar and interchangeable product marketplace? 
What can FDA do to ensure that confidence in these products among 
patients, healthcare providers, pharmacists, and other stakeholders 
will continue to grow?
    4. Extensive analytical characterization of the proposed biosimilar 
product and the reference product serves as the foundation for a 
demonstration of biosimilarity. FDA recognizes that obtaining and 
testing multiple lots of the reference product adds to the costs of 
developing a biosimilar product. What can FDA do to help reduce 
development costs arising from analytical studies of the reference 
product without compromising FDA's robust scientific standards for 
licensure of products under section 351(k) of the PHS Act? FDA is 
particularly interested in stakeholder comments on (1) the number of 
lots of each product (the proposed biosimilar product and the reference 
product) that should be used in analytical studies submitted to support 
licensure of a proposed biosimilar product; and (2) how a 351(k) 
applicant should account for and evaluate any observed variability in 
analytical attributes among lots of the reference product or the 
proposed biosimilar product.
    5. A 351(k) applicant may, with adequate scientific justification, 
use a non-U.S.-licensed comparator product in certain studies submitted 
to support licensure of a proposed biosimilar product. What additional 
steps can FDA take to facilitate multinational development programs 
that may include non-U.S.-licensed comparators, to help support 
development of biosimilar products?
    6. FDA expects continued innovation in the biological product 
marketplace, including innovation during the lifecycle of reference 
products licensed under section 351(a) of the PHS Act. What can FDA do 
to ensure that product changes during the lifecycle of reference 
products (e.g., changes in product presentation) are adequately 
incentivized without inappropriately deterring competition from 
biosimilar and interchangeable products, with the overall goal of 
balancing of innovation and competition?
    7. Patents or exclusivity may protect one or more conditions of use 
(e.g., indications) of the reference product. As a result, 351(k) 
applicants may seek licensure of the proposed biosimilar product for 
fewer than all of the conditions of use for which the reference product 
is licensed. Once a condition of use is no longer protected by patents 
or exclusivity, FDA anticipates that 351(k) applicants often will seek 
licensure of their product for this condition of use. What challenges 
do 351(k) applicants face in this context and what should FDA do to 
achieve the appropriate balance between innovation and competition when 
one or more conditions of use of the reference product are protected by 
exclusivity or patents?
    8. The scope of exclusivity under section 351(k)(7) of the PHS Act 
may also affect biological product innovation and market entry of 
biosimilars. Accordingly, FDA seeks comment on the potential 
application of ``umbrella exclusivity'' under section 351(k)(7). If 
umbrella exclusivity were to apply in this context, a biological 
product that would not be eligible for a new period of exclusivity 
under section 351(k)(7)(C) would nevertheless be protected for the 
duration of the exclusivity period for a previously approved reference 
product. See, for example, 54 FR 28872 at 28897 (July 10, 1989) for an 
explanation of how umbrella exclusivity functions under the Hatch-
Waxman scheme, a related and potentially instructive context (available 
at: https://cdn.loc.gov/service/ll/fedreg/fr054/fr054130/fr054130.pdf). 
Thus, umbrella exclusivity could help shield certain biological 
products that would otherwise not be eligible for their own period of 
exclusivity under section 351(k)(7)(C) from biosimilar competition. 
What considerations support recognition of umbrella exclusivity under 
section 351(k)(7), and what considerations disfavor recognizing 
umbrella exclusivity? How would umbrella exclusivity promote biological 
product innovation, and what effect would it have on market entry of 
biosimilars? What is the relevance and significance, if any, of the 
patent scheme in considering this issue?
    9. What other challenges have the potential to disrupt the balance 
between innovation and competition in the biological product 
marketplace and how can FDA or other stakeholders address these 
challenges?

III. Participating in the Public Hearing

    Registration and Requests for Oral Presentations: The FDA 
Conference Center at the White Oak location is a Federal facility with 
security procedures and limited seating. Attendance will be free and on 
a first-come, first-served basis. If you wish to attend (either in 
person or by webcast (see Streaming Webcast of the Public Hearing)) 
and/or present at the hearing, please register for the hearing and, if 
appropriate, request an oral presentation or participation in

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the open public hearing by sending an email to [email protected] 
by Tuesday, August 14, 2018. Requests for participation in the open 
public hearing are accepted until 9 a.m. on Tuesday September 4, 2018, 
and will be accepted as long as time allows. The email should contain 
complete contact information for each attendee (name, title, degree(s), 
affiliation, address, email address, and telephone number). For those 
wishing to present at the hearing, the email should also include a 
presentation title. Those without email access can register by 
contacting Allison Hoffman at 301-796-9203 by Tuesday, August 14, 2018 
(see FOR FURTHER INFORMATION CONTACT). An agenda for the hearing and 
any other background materials will be made available 5 days before the 
hearing at https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/UCM610692.htm.
    FDA will try to accommodate all persons who wish to make a 
presentation. Individuals wishing to present should identify the number 
of the specific question, or questions, they wish to address. This will 
help FDA organize the presentations. Individuals and organizations with 
common interests should consolidate or coordinate their presentations 
and request time for a joint presentation. FDA will notify registered 
presenters of their scheduled presentation times. The time allotted for 
each presenter will depend on the number of individuals who wish to 
speak. Presenters are encouraged to submit an electronic copy of their 
presentation (PowerPoint or PDF) to [email protected] on or 
before Thursday, August 16, 2018. Those who are not giving electronic 
presentations are encouraged to submit a single slide (PowerPoint or 
PDF) with their name, affiliation, and topic. Persons registered to 
make either an oral presentation or participate as part of the open 
public hearing are encouraged to arrive at the hearing room early and 
check in at the onsite registration table to confirm their designated 
presentation time. An agenda for the hearing and any other background 
materials will be made available 5 days before the hearing at https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm580561.htm.
    If you need special accommodations because of a disability, please 
contact [email protected] (see FOR FURTHER INFORMATION CONTACT) 
no later than Friday, August 17, 2018, at 12 noon Eastern Time.
    Streaming Webcast of the Public Hearing: For those unable to attend 
in person, FDA will provide a live webcast of the hearing. To join the 
hearing via the webcast, please go to https://collaboration.fda.gov/biosimilarspart15.
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at https://www.regulations.gov. It may 
be viewed at the Dockets Management Staff (see ADDRESSES).

IV. Notification of Hearing Under 21 CFR Part 15

    The Commissioner of Food and Drugs is announcing that the public 
hearing will be held in accordance with part 15 (21 CFR part 15). The 
hearing will be conducted by a presiding officer, who will be 
accompanied by FDA senior management from the Office of the 
Commissioner, the Center for Drug Evaluation and Research, and the 
Center for Biologics Evaluation and Research. Under Sec.  15.30(f) (21 
CFR 15.30(f)), the hearing is informal and the rules of evidence do not 
apply. No participant may interrupt the presentation of another 
participant. Only the presiding officer and panel members can pose 
questions; they can question any person during or at the conclusion of 
each presentation. Public hearings under part 15 are subject to FDA's 
policy and procedures for electronic media coverage of FDA's public 
administrative proceedings (21 CFR part 10, subpart C). Under 21 CFR 
10.205, representatives of the media may be permitted, subject to 
certain limitations, to videotape, film, or otherwise record FDA's 
public administrative proceedings, including presentations by 
participants. The hearing will be transcribed as stipulated in Sec.  
15.30(b) (see Transcripts). To the extent that the conditions for the 
hearing, as described in this notification, conflict with any 
provisions set out in part 15, this notification acts as a waiver of 
those provisions as specified in Sec.  15.30(h).

    Dated: July 19, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-15859 Filed 7-24-18; 8:45 am]
 BILLING CODE 4164-01-P