[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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.
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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
[[Page 22501]]
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