[Federal Register Volume 84, Number 120 (Friday, June 21, 2019)]
[Proposed Rules]
[Pages 29112-29114]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-13219]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 15

[Docket No. FDA-2019-N-2514]


Standards for Future Opioid Analgesic Approvals and Incentives 
for New Therapeutics To Treat Pain and Addiction; Public Hearing

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, Agency, we) is holding 
a public hearing on September 17, 2019, entitled ``Standards for Future 
Opioid Analgesic Approvals and Incentives for New Therapeutics to Treat 
Pain and Addiction.'' The Agency today is issuing a draft guidance on 
the application of FDA's existing benefit-risk assessment framework to 
applications for approval of opioid analgesic drugs. This public 
hearing is intended to receive stakeholder input on the approval 
process for new opioids and how FDA might best consider the existing 
armamentarium of therapies, among other factors, in reviewing 
applications for new opioids to treat pain. FDA also seeks input on 
potential new preapproval incentives aimed at fostering the development 
of new therapeutics to treat pain, as well as new treatments for 
addiction.

DATES: The public hearing will be held on September 17, 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 can attend the 
event in person or via webcast. In-person attendees can also request to 
give a formal presentation or to speak during the open public comment 
portion of the hearing. Section II provides attendance and registration 
information. Electronic or written comments will be accepted after the 
public hearing until November 18, 2019.

ADDRESSES: The public hearing will be held at the FDA White Oak Campus, 
10903 New Hampshire Ave., Building 31 Conference Center, the Great Room 
(Rm. 1503 B/C), 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 November 18, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of November 18, 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. You may submit 
comments 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-2019-N-2514 for ``Standards for Future Opioid Analgesic Approvals 
and Incentives for New Therapeutics to Treat Pain and Addiction; Public 
Hearing.'' 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.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the received electronic and written/paper comments, 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: Nicole Zelenak, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6249, Silver Spring, MD 20993, 301-796-
9030; [email protected].

SUPPLEMENTARY INFORMATION:

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I. Background

    The Substance Use-Disorder Prevention that Promotes Opioid Recovery 
and Treatment for Patients and Communities Act (or SUPPORT for Patients 
and Communities Act) \1\ was signed into law on October 24, 2018. One 
provision of this law requires FDA to hold not less than one public 
meeting to address the challenges and barriers of developing non-
addictive medical products intended to treat acute or chronic pain or 
addiction, which may include the manner in which the risks of abuse or 
misuse of a controlled substance may be incorporated into the benefit-
risk assessment for new drug approvals under section 505(d) and (e) of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(d) and (e)).\2\
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    \1\ Public Law 115-271.
    \2\ Id., section 3001(a).
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    All opioids approved to treat pain are controlled substances. They 
are a crucial component of the armamentarium available for treatment of 
pain, but they carry serious risks of addiction, overdose, and death. 
Potent novel analgesics that do not carry these risks could 
significantly reduce or even obviate the need for opioid analgesics, 
but development of such drugs has remained elusive. FDA is optimistic 
that the enormous societal need, and the efforts of all stakeholders to 
meet that need, will drive scientific advances in the development of 
novel, safer analgesics. In the meantime, however, opioid analgesics 
are likely to remain a necessary part of medical practice despite their 
risks. FDA's goal is to regulate opioid analgesics in such a way as to 
reduce their serious risks to the greatest extent possible, while 
ensuring their continued availability to the patients who need them.
    Under our existing authorities, FDA determines whether each new 
drug application--including each new opioid drug application--meets 
applicable standards for safety and effectiveness. In applying these 
standards, FDA evaluates whether the benefits of the drug outweigh its 
risks. Benefit-risk assessment is the foundation of FDA's regulatory 
review of human drugs and biologics. It reflects the Agency's 
consideration of the evidence, identification of uncertainties, and the 
reasoning the Agency uses to make specific regulatory decisions, 
including product approvals. Additionally, the benefit-risk assessment 
for a particular medical product serves as a tool for communicating the 
Agency's findings about the product.
    FDA today issued a draft guidance on the application of FDA's 
benefit-risk assessment framework to applications for approval of 
opioid analgesic drugs entitled ``Opioid Analgesic Drugs: 
Considerations for Benefit-Risk Assessment Framework--Guidance for 
Industry.'' This draft guidance discusses the Agency's application of 
the existing benefit-risk assessment framework, which takes into 
account not only the benefits and risks of a proposed new opioid to 
patients when used as prescribed, but also the effectiveness and safety 
of the proposed product relative to currently available analgesics as 
well as the public health impact of anticipated inappropriate use. 
Comments on that draft guidance may be submitted to the docket number 
for the draft guidance, FDA-2019-D-1536. Comments are requested to be 
submitted by [enter DATE that is 60 days after issuance of the draft 
guidance] to ensure that your comments will be considered before 
finalization of the guidance.
    The existing benefit-risk assessment process has been, and 
continues to be, a comprehensive and effective mechanism for evaluating 
all new drug approvals, including new opioid approvals. Given the 
current opioid crisis, however, it is critical that FDA explore every 
possible option for effectively responding to opioid misuse and abuse. 
To this end, the Agency is announcing this public hearing to gather 
input on additional factors the Agency could consider during the 
approval process for new opioid therapies. For example, should a new 
opioid analgesic be required to demonstrate an advantage over existing 
drugs to justify its addition to the market? If so, what new 
authorities would FDA need to impose such a requirement? What other new 
authorities might FDA need to fully assess candidate opioid analgesics 
given their serious risks and the societal impact of opioids overall?
    As noted above, potent novel analgesics that do not carry the 
serious risks of existing opioids could greatly reduce or even 
eliminate the need for opioid analgesics in the armamentarium of drugs 
available to treat serious pain. In addition, there is an urgent need 
for new and better treatment options for opioid use disorder. 
Accordingly, FDA is also considering whether new preapproval incentives 
(in addition to existing incentives, such as breakthrough designation) 
are needed to better support and encourage development of all 
therapeutics (opioid or non-opioid drugs, biological products, or 
devices) intended to treat pain or addiction. Such new incentives could 
be tailored to the development of novel analgesics and could include, 
among other things, an FDA commitment to hold a series of meetings and 
provide written feedback at various stages of product development, with 
a firm seeking approval of a product with the potential to offer an 
advantage relative to existing products indicated to treat pain or 
addiction. We invite comment on potential new incentives as discussed 
below.

II. Topics for Discussion at the Public Hearing

    FDA is seeking feedback from a broad group of stakeholders, both 
private and public, who are working on the challenges of improving pain 
management and addressing the opioid crisis. Some questions for 
consideration at the public hearing are provided below. We welcome 
input on other relevant issues as well.
    1. Does the current statutory and regulatory framework, including 
the benefit-risk assessment described in the recently issued draft 
guidance, allow for an adequate evaluation of applications for new 
opioid analgesics, or are new authorities required? If new authorities 
are required, please expand on what should be added to the existing 
statutory and regulatory paradigm.
    2. Should sponsors of new opioid analgesics be required to 
demonstrate some comparative advantage relative to existing analgesics? 
If so, what new authorities would be necessary to impose a comparative 
advantage requirement for opioid analgesics?
    3. If so, how should that comparative advantage be defined?
    a. Can it be quantified?
    b. Should the assessment encompass any potential comparative 
advantage, including, e.g., safety advantages that reduce the 
prevalence or consequences of abuse or misuse by non-patient 
populations?
    c. For any given application, to which existing products should the 
proposed new product be required to demonstrate comparative advantage? 
Any other opioid approved for the same analgesic indication(s) for 
which approval is sought? What are the implications if the new product 
only offers a comparative advantage over some of the other opioid 
products approved for the same indication(s)?
    4. If a showing of comparative advantage were made a requirement 
for approval of new opioid analgesics, could a proposed product meet 
this standard even if the product also carried additional or novel 
risks compared to existing products?
    5. If a showing of comparative advantage were made a requirement 
for approval of new opioid analgesics, should there be any exceptions, 
for

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example with regard to medically necessary drugs in shortage?
    6. If a showing of comparative advantage were made a requirement 
for approval of new opioid analgesics, what would be the impact on 
development of such products?
    7. If a showing of comparative advantage were made a requirement 
for approval of new opioid analgesics, what would be the impact on 
patients, providers, and on the public health generally? Please 
consider that the existing opioid market consists largely of relatively 
inexpensive generic drugs.
    8. In what other ways should FDA be considering the existing 
armamentarium of therapies to treat pain when reviewing an application 
for the approval of a new opioid analgesic? To what extent would new 
authorities be required?
    9. Please comment on whether new pre-approval incentives are needed 
to better support and encourage development of therapeutics intended to 
treat pain or addiction. If so, what new incentives would be most 
effective, and what new authorities might FDA need to offer them? If 
the new incentives are offered through a designation process (analogous 
to breakthrough designation), what should be the criteria for 
designation?
    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. Attendees can register at 
https://www.eventbrite.com/e/fda-standards-for-future-opioid-therapy-approvals-part-15-meeting-tickets-60645674846. Attendees have the 
following options:
     Presenter--Presenters will give a timed presentation 
followed by a timed question and answer period by the panel. The 
presentation time allotted will be approximately 10 minutes, but this 
is subject to change based on the number of presenters who register. 
Presenters can opt to use a presentation slide deck. Presenters must 
register no later than August 9, 2019. Slide decks are due to [email protected] in PDF or PowerPoint format no later than 
August 23, 2019. If presenters choose to not use a slide deck, they are 
requested to submit a single slide with name of presentation and 
contact information by September 6, 2019.
     Open Public Commenter--Open public commenters will provide 
a timed oral testimony. The comment time allotted will be approximately 
3 minutes, but this is subject to change based on the number or 
commenters who register. Open public commenters shall not have 
presentation materials or a question and answer period with the panel. 
Commenters must register no later than September 10, 2019.
     In-Person Attendee--In-person attendees will attend the 
meeting at the FDA White Oak facility.
     Webcast Attendee--For those unable to attend in person, 
FDA will provide a live webcast of the hearing. Webcast attendees will 
be provided with a link via email to use to view the streaming webcast 
of the public hearing.
    Attendees shall register for only one person. Those without 
internet or email access can register and/or request to participate as 
an open public hearing speaker or a formal presenter by contacting 
Nicole Zelenak by the above dates (see FOR FURTHER INFORMATION 
CONTACT).
    FDA will try to accommodate all persons who wish to register. 
Registration may close early if slots are full. Individuals and 
organizations with common interests may consolidate or coordinate 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 no 
later than 1 week prior to the meeting. The time allotted for each 
presentation will depend on the number of individuals who wish to 
speak. 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. An 
agenda for the hearing and any other background materials will be made 
available 5 days before the hearing at https://www.fda.gov/drugs/development-approval-process-drugs/standards-future-opioid-therapy-approvals-09172019-09172019.
    If you need special accommodations because of a disability, please 
contact Nicole Zelenak (see FOR FURTHER INFORMATION CONTACT) at least 7 
days before the hearing.
    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 Comments). A transcript 
will also be available in either hard copy or on CD-ROM, after 
submission of a Freedom of Information request. The Freedom of 
Information office address is available on the Agency's website at 
https://www.fda.gov.

III. 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 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, Center for Biologics Evaluation and 
Research, and the Center for Devices and Radiological Health. Under 
Sec.  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 Sec.  
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 public hearings are advised that 
FDA 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 notice, conflict with any provisions set out in part 
15, this notice acts as a waiver of those provisions as specified in 
Sec.  15.30(h).

    Dated: June 17, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-13219 Filed 6-20-19; 8:45 am]
 BILLING CODE 4164-01-P