[Federal Register Volume 84, Number 64 (Wednesday, April 3, 2019)]
[Proposed Rules]
[Pages 12966-12969]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-06438]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 15

[Docket No. FDA-2019-N-1132]


The Future of Insulin Biosimilars: Increasing Access and 
Facilitating the Efficient Development of Biosimilar and 
Interchangeable Insulin Products; 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 to discuss access to affordable insulin 
products and issues related to the development and approval of 
biosimilar and interchangeable insulin products.

DATES: The public hearing will be held on May 13, 2019, 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 present at the 
public hearing must register by April 29, 2019. Persons seeking to 
speak at the public hearing must register by May 9, 2019. Persons 
seeking to attend, but not present at, the public hearing must register 
by May 9, 2019. Section III provides attendance and registration 
information. Electronic or written comments will be accepted after the 
public hearing until May 31, 2019.

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. 1503B), 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 May 31, 2019. The https://www.regulations.gov 
electronic filing system will accept comments until 11:59 p.m. Eastern 
Time at the end of May 31, 2019. 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-2019-N-1132 for ``The Future of Insulin Biosimilars: Increasing 
Access and Facilitating the Efficient Development of Insulin Biosimilar 
and Interchangeable Products; Public Hearing; Request for Comments.'' 
Received comments, those filed in a timely manner (see

[[Page 12967]]

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 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.

FOR FURTHER INFORMATION CONTACT: Allison Hoffman, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 3138, Silver 
Spring, MD 20993, 301-796-9203, [email protected] (please use 
``Insulin Biosimilars part 15'' as subject line).

SUPPLEMENTARY INFORMATION: 

I. Background

    The Biologics Price Competition and Innovation Act of 2009 (BPCI 
Act) requires that on March 23, 2020, an approved marketing application 
for a biological product under section 505 of the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) (21 U.S.C. 355) will be deemed to be a 
license for the biological product under section 351 of the Public 
Health Service Act (PHS Act) (42 U.S.C. 262) and regulated under the 
PHS Act. The transition of biological products currently approved under 
the FD&C Act to the PHS Act will open the pathway to market for new 
products that are biosimilar to, or interchangeable with, these 
transitioned products. The biological products affected by this 
transition include insulin products, insulin mix products, and insulin 
analog products (collectively described in this notification as 
``insulin products''), which historically have been approved under the 
FD&C Act.
    Insulin is a lifesaving drug that many Americans depend on to treat 
their diabetes. In recent years, however, increases in the prices of 
insulin products have raised serious concerns about the ability for 
many patients to access the insulin needed to survive. FDA is holding 
this public hearing to receive input from stakeholders as the Agency 
prepares for the submission and review of applications for biosimilar 
and interchangeable insulin products. FDA anticipates that these 
products, once they are approved, will bring new competition to the 
insulin market and help provide affordable treatment options to 
patients with diabetes without compromising safety and effectiveness.
    The BPCI Act amended the 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. This abbreviated pathway allows an applicant to rely 
on certain existing knowledge about the safety and effectiveness of a 
biological reference product to support approval, provided the sponsor 
can demonstrate that its product meets the applicable statutory 
standards, including biosimilarity. Thus, the sponsor may be able to 
develop the biosimilar at a lower cost, relative to the development of 
a novel biological product submitted in a stand-alone marketing 
application. The PHS Act defines biosimilarity to mean ``that the 
biological product is highly similar to the reference product 
notwithstanding minor differences in clinically inactive components'' 
and that ``there are no clinically meaningful differences between the 
biological product and the reference product in terms of the safety, 
purity, and potency of the product'' (section 351(i)(2) of the PHS 
Act).
    An interchangeable biosimilar may be substituted for the reference 
product without the intervention of the prescribing healthcare provider 
(see section 351(i)(3) of the PHS Act). To meet the standard of 
``interchangeability,'' an applicant must provide sufficient 
information to demonstrate: (1) Biosimilarity; (2) that the biological 
product can be expected to produce the same clinical result as the 
reference product in any given patient; and (3) for products 
administered more than once to an individual, that the risk in terms of 
safety or diminished efficacy of alternating or switching between the 
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(k)(4) of the PHS Act).
    After the March 23, 2020, transition, insulin products that will be 
deemed to be licensed under the PHS Act will be able to act as 
reference products for proposed biosimilar or interchangeable insulin 
products. There are currently no approved prescription insulin products 
that can be substituted at the pharmacy level. An interchangeable 
insulin product can be substituted for the reference insulin product at 
the pharmacy, potentially leading to increased access and lower costs 
for patients.
    This public hearing is a component of FDA's broader effort to 
facilitate the growth of a competitive market for biologics. In July 
2018, FDA issued its Biosimilars Action Plan, which focuses on four 
areas of FDA activities: (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. On 
September 4, 2018, FDA held a public meeting entitled ``Facilitating 
Competition and Innovation in the Biological Products Marketplace'' 
(see 83 FR 35154, July 25, 2018) and received submissions to an 
associated docket (Docket No. FDA-2018-N-2689).

II. Purpose and Scope of the Public Hearing

    FDA is holding this public hearing to receive input from patients, 
families,

[[Page 12968]]

healthcare providers, and other stakeholders who live with diabetes or 
care for someone with diabetes about the challenges and opportunities 
FDA should consider as we prepare for the submission and review of 
applications for biosimilar and interchangeable insulin products. We 
also want to hear from manufacturers and other stakeholders about the 
development process for biosimilar and interchangeable insulin 
products. FDA has determined that a public hearing is the most 
appropriate way to ensure public engagement on these topics.
    Questions for Commenters to Address: FDA is soliciting input on 
steps the Agency can take to facilitate increased access to insulin 
products, including biosimilar and interchangeable insulin products. 
FDA is interested in how we can encourage the development of biosimilar 
and interchangeable insulin products, while achieving the balance 
between competition and innovation intended by Congress in the BPCI 
Act. Although FDA welcomes all feedback on any public health, 
scientific, regulatory, or legal considerations relating to this topic, 
we particularly encourage commenters to consider the following topics 
and questions as they prepare their comments or statements.
    1. Scientific standards for evaluating the biosimilarity and 
interchangeability of an insulin product.
    a. What considerations should FDA take into account when evaluating 
data and other information submitted by an applicant, including from 
analytical and clinical studies, to determine whether an insulin 
product is biosimilar to a reference product?
    b. What considerations should FDA take into account when evaluating 
data and other information submitted by an applicant, to determine 
whether an insulin product is interchangeable with a reference product?
    2. Other regulatory considerations: Do certain insulin products, 
for example, those that include use in insulin pumps for continuous 
subcutaneous infusion among the approved uses or those approved with 
over-the-counter marketing status, raise unique scientific 
considerations? What factors should FDA consider when evaluating a 
proposed biosimilar or interchangeable insulin product if the reference 
product raises such considerations? Are there additional factors FDA 
should evaluate for interchangeable insulin products, which may be 
substituted at the pharmacy for the reference product without the 
involvement of the prescriber?
    3. Patient experience: What aspects of the patient experience with 
insulin products should FDA consider when evaluating a proposed 
biosimilar or interchangeable insulin product?
    4. Information resources for patients, clinicians, pharmacists, and 
other stakeholders: What information is needed to develop effective 
communications to improve understanding and promote awareness among 
patients, clinicians, pharmacists, and other stakeholders about 
biosimilar and interchangeable insulin products?

III. Participating in the Public Hearing

    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. An agenda for the 
hearing and any other background materials will be made available 5 
days before the hearing at https://www.fda.gov/FDAgov/NewsEvents/MeetingsConferencesWorkshops/ucm632081.htm. If you need special 
accommodations because of a disability, please contact Allison Hoffman 
(see FOR FURTHER INFORMATION CONTACT) at least 7 days before the 
hearing.
    Registration and Requests for Formal Oral Presentations: For those 
interested in presenting at the meeting with a formal oral 
presentation, please register at https://www.eventbrite.com/e/insulin-biosimilar-part-15-tickets-56571622245 as ``In-person presenter''. 
Presenter registrations are due April 29, 2019.
    FDA will try to accommodate all persons who wish to make a formal 
oral presentation. Formal oral presenters may use an accompanying slide 
deck. Individuals wishing to present should identify their name, 
affiliation (if appropriate), and 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 consider consolidating or coordinating their presentations and 
request time for a joint presentation. Individual organizations are 
limited to a single presentation slot. FDA will notify registered 
presenters of their scheduled presentation times. The time allotted for 
each presentation will depend on the number of individuals who wish to 
speak. Registered presenters making a formal oral presentation are 
encouraged to submit an electronic copy of their presentation 
(PowerPoint or PDF) to [email protected] with the subject line 
``Insulin Biosimilars part 15 Presentation'' on or before May 6, 2019. 
Persons registered to present are encouraged to arrive at the hearing 
room early and check in at the onsite registration table to confirm 
their designated presentation time. Actual presentation times, however, 
may vary based on how the meeting progresses in real time.
    Registration and Requests for Open Public Hearing Speaker slots: 
For those interested in participating as an Open Public Hearing 
speaker, please register at https://www.eventbrite.com/e/insulin-biosimilar-part-15-tickets-56571622245 as ``In-person Open Public 
Hearing presenter''. Open Public Hearing registrations are due May 9, 
2019; however, you may sign up as an Open Public Hearing speaker the 
day of the meeting. Time and space are limited and available on a 
first-come, first-served basis. Open Public Hearing speakers have less 
allotted time than formal oral presenters and will deliver oral 
testimony only (no accompanying slide deck).
    Persons registered to participate during the Open Public Hearing 
are encouraged to arrive at the hearing room early and check in at the 
onsite registration table to confirm their Open Public Hearing 
participation.
    Those without internet or email access can request to participate 
as a formal presenter or an open public hearing speaker by contacting 
Allison Hoffman by the above dates (see FOR FURTHER INFORMATION 
CONTACT).
    In-person attendance: For those who would like to attend in-person, 
but who are not making a formal presentation or participating in the 
Open Public Hearing, please register at https://www.eventbrite.com/e/insulin-biosimilar-part-15-tickets-56571622245 as ``In-person 
attendee--no participation''. You may choose not to register; however, 
seating is limited, and space will be available on a first-come, first-
served basis.
    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/insulin051319. Please register at https://www.eventbrite.com/e/insulin-biosimilar-part-15-tickets-56571622245 as ``online (webcast only)''.
    Media: Please register at https://www.eventbrite.com/e/insulin-biosimilar-part-15-tickets-56571622245 as ``Media'' by May 9, 2019.
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at https://www.fda.gov/FDAgov/NewsEvents/MeetingsConferencesWorkshops/ucm632081.htm and https://www.regulations.gov. It may be viewed at the Dockets Management Staff 
(see ADDRESSES).

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IV. Notice 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 Devices and Radiological Health, the 
Center for Drug Evaluation and Research, and the Office of the Chief 
Counsel. 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. 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. Persons attending FDA's hearings are 
advised that the Agency is not responsible for providing access to 
electrical outlets. 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: March 28, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-06438 Filed 4-2-19; 8:45 am]
 BILLING CODE 4164-01-P


