[Federal Register Volume 79, Number 77 (Tuesday, April 22, 2014)]
[Notices]
[Pages 22499-22501]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-09123]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-0374]


Postmarketing Requirements for the Class-Wide Extended-Release/
Long-Acting Opioid Analgesics; Public Meeting; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public meeting; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a public 
meeting to obtain stakeholder input on the design and conduct of the 
postmarketing requirements (PMRs) for the class-wide extended-release/
long-acting (ER/LA) opioid analgesic drug products to further assess 
the serious risks of misuse, abuse, hyperalgesia, addiction, overdose, 
and death associated with their long-term use.
    FDA is seeking input on these issues from stakeholders, including 
patients, academia, researchers, State and other Federal regulators, 
health care organizations, health care providers, the pharmaceutical 
industry, and others from the general public.

DATES: The public meeting will be held on May 19 and 20, 2014, from 8 
a.m. to 5 p.m. Individuals who wish to present at the meeting must 
register by May 9, 2014. See section III under the SUPPLEMENTARY 
INFORMATION section for information on how to register to speak at the 
meeting.

ADDRESSES: The public meeting will be held at FDA's White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room 
(Rm. 1503), Silver Spring, MD 20993-0002. Participants must enter 
through Building 1 and undergo security screening. For parking and 
security information, please refer to http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    Submit either electronic or written comments by June 19, 2014. 
Submit electronic comments to http://www.regulations.gov. Submit 
written comments to the Division of Dockets Management (HFA-305), Food 
and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 
20852. Identify all comments with the docket number found in brackets 
in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Janelle Derbis, Center for Drug 
Evaluation and Research, Food and Drug Administration, 20 North 
Michigan Ave., Suite 510, Chicago, IL 60602, 312-596-6516, FAX: 312-
886-

[[Page 22500]]

1682, email: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is committed to improving the safe and appropriate use of ER/LA 
opioid analgesics and preserving appropriate access for those patients 
who rely on these medications to manage their pain. In May 2012, FDA 
hosted a scientific workshop to discuss the assessment of analgesic 
treatment of chronic pain, during which presenters raised concerns 
about the safe and appropriate use of opioid analgesics.\1\ Over the 
past 2 years, FDA has reviewed numerous submissions to Agency dockets, 
including citizen petitions and comments to petitions, and relevant 
literature about the benefits and risks associated with opioid drug 
products, including the serious risks of misuse, abuse, hyperalgesia, 
addiction, overdose, and death associated with the long-term use of ER/
LA opioid analgesics. FDA has concluded that more data are needed 
regarding these serious risks.
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    \1\ Assessment of Analgesic Treatment of Chronic Pain: A 
Scientific Workshop (see http://www.fda.gov/Drugs/NewsEvents/ucm283979.htm). Information and comments from that workshop are 
available at www.regulations.gov, Docket No. FDA-2012-N-0067.
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    FDA described these data requirements in its September 10, 2013, 
letter to all new drug application (NDA) applicants for ER/LA opioid 
analgesics. Data are needed to address the following issues:
     The incidence of and risk factors for misuse, abuse, 
addiction, overdose, and death associated with long-term use of opioids 
for chronic pain.
     Validated measures of misuse, abuse, addiction, overdose, 
and death.
     Validated coded medical terminologies used to identify 
misuse, abuse, addiction, overdose, and death.
     Validated definitions of ``doctor/pharmacy shopping'' as 
outcomes suggestive of misuse, abuse, and addiction.
     The serious risk of developing hyperalgesia following use 
of ER/LA opioid analgesics for at least 1 year to treat chronic pain.
    In the September 10, 2013, letter, FDA informed the ER/LA opioid 
analgesic NDA application holders of the requirement to conduct 
postapproval studies (also referred to as postmarketing requirements or 
PMRs) and established milestone dates for completion of those studies, 
which include observational studies and a clinical trial (see section 
II for more details). The deadline for the applicants' final protocol 
submissions is August 2014.

II. Purpose and Scope of Meeting

    The purpose of this public meeting is to obtain stakeholder input 
on the design and conduct of the PMRs (described in the following 
paragraph) for the ER/LA opioid analgesic drug products to assess the 
serious risks of misuse, abuse, hyperalgesia, addiction, overdose, and 
death associated with their long-term use. FDA and NDA applicants will 
consider stakeholder input when preparing final protocols to be 
submitted by August 2014.
    The PMRs described in FDA's September 10, 2013, letter to NDA 
applicants of ER/LA opioid analgesics are as follows:
    (1) PMR  2065-1: Conduct one or more studies to provide 
quantitative estimates of the serious risks of misuse, abuse, 
addiction, overdose, and death associated with long-term use of opioid 
analgesics for management of chronic pain among patients prescribed ER/
LA opioid products. Include an assessment of risk relative to efficacy.
    These studies should address at a minimum the following specific 
aims:
    a. Estimate the incidence of misuse, abuse, addiction, overdose, 
and death associated with long-term use of opioids for chronic pain. 
Stratify misuse and overdose by intentionality wherever possible. 
Examine the effect of product/formulation, dose and duration of opioid 
use, prescriber specialty, indication, and other clinical factors 
(e.g., concomitant psychotropic medications, personal or family history 
of substance abuse, and history of psychiatric illness) on the risk of 
misuse, abuse, addiction, overdose, and death.
    b. Evaluate and quantify other risk factors for misuse, abuse, 
addiction, overdose, and death associated with long-term use of opioids 
for chronic pain, including, but not limited to, the following: 
Demographic factors, psychosocial/behavioral factors, medical factors, 
and genetic factors. Identify confounders and effect modifiers of 
individual risk factor/outcome relationships. Stratify misuse and 
overdose by intentionality wherever possible.
    (2) PMR  2065-2: Develop and validate measures of the 
following opioid-related adverse events: Misuse, abuse, addiction, 
overdose, and death (based on the Department of Health and Human 
Services' definition, or any agreed upon definition), which will be 
used to inform the design and analysis for PMR  2065-1 and any 
future postmarketing safety studies and clinical trials to assess these 
risks. This can be achieved by conducting an instrument development 
study or a validation study of an algorithm based on secondary data 
sources.
    (3) PMR  2065-3: Conduct a study to validate coded medical 
terminologies (e.g., ICD9, ICD10, and SNOMED) used to identify the 
following opioid-related adverse events: Misuse, abuse, addiction, 
overdose, and death in any existing postmarketing databases to be 
employed in the studies. Stratify misuse and overdose by intentionality 
wherever possible. These validated codes will be used to inform the 
design and analysis for PMR  2065-1.
    (4) PMR  2065-4: Conduct a study to define and validate 
``doctor/pharmacy shopping'' as outcomes suggestive of misuse, abuse, 
and addiction. These validated codes will be used to inform the design 
and analysis for PMR  2065-1.
    (5) PMR  2065-5: Conduct a clinical trial to estimate the 
serious risk for the development of hyperalgesia following use of ER/LA 
opioid analgesics for at least 1 year to treat chronic pain. We 
strongly encourage you to use the same trial to assess the development 
of tolerance following use of ER/LA opioid analgesics. Include an 
assessment of risk relative to efficacy.

III. Attendance and Registration

    Attendance is free and will be on a first-come, first-served basis. 
Individuals who wish to present at the public meeting must register on 
or before May 9, 2014, at https://erlaopioidpmrmeeting.eventbrite.com. 
In section II, FDA has listed the PMRs. You should identify which 
PMR(s) you wish to address in your presentation, or whether your 
comments apply to all PMRs, so FDA can consider that in organizing the 
presentations. FDA will do its best to accommodate requests to speak 
and will determine the amount of time allotted to each presenter and 
the approximate time that each oral presentation is scheduled to begin. 
An agenda and additional meeting background material will be available 
approximately 2 weeks before the meeting at http://www.fda.gov/Drugs/NewsEvents/ucm384489.htm.
    Individuals who wish to attend the meeting but do not wish to make 
a presentation should register by May 12, 2014. Onsite registration on 
the day of the meeting will be based on space availability.
    If you need special accommodations due to a disability, please 
contact Janelle Derbis (see FOR FURTHER

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INFORMATION CONTACT) at least 7 days in advance.
    A live Web cast of this meeting will be viewable at https://collaboration.fda.gov/opmr/ on the day of the meeting. A video record 
of the meeting will be available at the same Web address for 1 year.

IV. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. To ensure 
consideration, submit comments by June 19, 2014. Received comments may 
be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

V. Transcripts

    As soon as possible after a transcript of the public meeting is 
available, it will be accessible at http://www.regulations.gov. It may 
be viewed at the Division of Dockets Management (see ADDRESSES). A 
transcript will also be available in either hardcopy or on CD-ROM, 
after submission of a Freedom of Information request. Written requests 
are to be sent to the Division of Freedom of Information (ELEM-1029), 
Food and Drug Administration, 12420 Parklawn Dr., Element Bldg., 
Rockville, MD 20857.

    Dated: April 17, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-09123 Filed 4-21-14; 8:45 am]
BILLING CODE 4160-01-P