Notice2022-08372
Providing Mail-Back Envelopes and Education on Safe Disposal With Opioid Analgesics Dispensed in an Outpatient Setting; Establishment of a Public Docket; Request for Comments
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Published
April 21, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is announcing the establishment of a docket to solicit public comment on a potential modification to the Opioid Analgesic Risk Evaluation and Mitigation Strategy (OA REMS) to require that mail-back envelopes be dispensed and education on safe disposal provided with opioid analgesics dispensed in an outpatient setting. Such a requirement could reduce the amount of unused opioid analgesics in patients' homes, thereby reducing opportunities for nonmedical use, accidental exposure, and overdose, and possibly reducing the development of new opioid addiction.
Full Text
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<title>Federal Register, Volume 87 Issue 77 (Thursday, April 21, 2022)</title>
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[Federal Register Volume 87, Number 77 (Thursday, April 21, 2022)]
[Notices]
[Pages 23869-23876]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-08372]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-N-0165]
Providing Mail-Back Envelopes and Education on Safe Disposal With
Opioid Analgesics Dispensed in an Outpatient Setting; Establishment of
a Public Docket; Request for Comments
AGENCY: Food and Drug Administration, Health and Human Services (HHS).
ACTION: Notice; establishment of a public docket; request for comments.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
announcing the establishment of a docket to solicit public comment on a
potential modification to the Opioid Analgesic Risk Evaluation and
Mitigation Strategy (OA REMS) to require that mail-back envelopes be
dispensed and education on safe disposal provided with opioid
analgesics dispensed in an outpatient setting. Such a requirement could
reduce the amount of unused opioid analgesics in patients' homes,
thereby reducing opportunities for nonmedical use, accidental exposure,
and overdose, and possibly reducing the development of new opioid
addiction.
DATES: Submit either electronic or written comments by June 21, 2022.
ADDRESSES: FDA is establishing a docket for public comment on this
notice. The docket number is FDA-2022-N-0165. The docket will close on
June 21, 2022. Submit either electronic or written comments by June 21,
2022. Please note that late, untimely filed comments will not be
considered. Electronic comments must be submitted on or before June 21,
2022. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will
accept comments until 11:59 p.m. Eastern Time at the end of June 21,
2022. 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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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:
<bullet> 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.
<bullet> 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-2022-N-0165 for ``Providing Mail-Back Envelopes and Education on
Safe Disposal With Opioid Analgesics Dispensed in an Outpatient
Setting; Establishment of a Public Docket; 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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: Patrick Raulerson, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6260, Silver Spring, MD 20993, 301-796-
3522, <a href="/cdn-cgi/l/email-protection#5f0f3e2b2d363c34710d3e2a333a2d2c30311f393b3e7137372c71383029"><span class="__cf_email__" data-cfemail="3b6b5a4f4952585015695a4e575e494854557b5d5f5a15535348155c544d">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Nonmedical use,\1\ accidental exposure, and overdose associated
with prescription opioid analgesics remain a serious problem in the
United States. In 2019, prescription pain relievers, such as opioid
analgesics, remained the most common class of prescription drugs used
nonmedically in the United States, with approximately 9.7 million
people aged 12 and older reporting past-year nonmedical use (Ref. 1).
Many people who use opioids nonmedically start with prescription opioid
analgesics and transition to illicit substances (Refs. 2 to 5). Also,
from 2010 to 2018 there were over 48,000 accidental prescription opioid
exposures in young children (Ref. 6).
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\1\ We use the term ``nonmedical'' in this document to refer to
misuse of a drug, abuse of a drug, or both. ``Misuse'' is the
intentional use, for therapeutic purposes, of a drug in a manner
other than prescribed. ``Abuse'' is the intentional, non-therapeutic
use of a drug, even once, for its desirable psychological or
physiological effects.
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While the volume of prescription opioid analgesics dispensed has
been
[[Page 23870]]
trending downward following a peak in 2012, there were still an
estimated 140.6 million prescriptions, resulting in an estimated 8.7
billion units (e.g., tablets or capsules) dispensed in 2021 from U.S.
outpatient retail and mail order pharmacies (Ref. 7). As of 2020,
despite the decrease in opioid dispensing, prescription opioids were
involved in more than 16,000 fatal overdoses per year (Ref. 8), higher
than the number seen at the peak of opioid analgesic dispensing in 2012
(Ref. 9). The lethality of co-involved substances, such as heroin,
illicitly manufactured fentanyl, and illicitly manufactured fentanyl
analogues has also changed since 2012 and may partly explain why
overdose deaths involving opioid analgesics persist, despite the
reductions in prescribing.
Patients commonly report having unused opioid analgesics after
treatment of acute pain, such as pain following surgical procedures
(Refs. 10 and 11). Opioid analgesics prescribed to treat chronic pain
conditions can also result in unused drugs. When not properly disposed,
these opioid analgesics provide opportunities for nonmedical use,
accidental exposure, and overdose. Most people who reported past-year
nonmedical use of prescription pain relievers obtained them through
friends, relatives, or their own prescription (Ref. 1). Accordingly,
FDA's efforts to address the opioid crisis include a focus on
encouraging appropriate disposal of unused opioid analgesics.
The Substance Use-Disorder Prevention that Promotes Opioid Recovery
and Treatment for Patients and Communities Act (SUPPORT Act) (Pub. L.
115-271), signed into law on October 24, 2018, provides FDA several new
authorities to address the opioid crisis. The SUPPORT Act authorized
FDA to require through a Risk Evaluation and Mitigation Strategy (REMS)
that a safe disposal packaging or safe disposal system for the purposes
of rendering the drug nonretrievable be dispensed to certain patients
with opioids or other drugs that pose a serious risk of abuse or
overdose if, among other things, FDA determines that such safe disposal
packaging or system may mitigate such risks and is sufficiently
available (21 U.S.C. 355-1(e)(4)).
The purpose of this notice is to seek public comment on the
potential application of this authority to require, under the Opioid
Analgesic (OA) REMS, that mail-back envelopes and education on safe
disposal be provided with opioid analgesics dispensed in outpatient
settings. We recognize that this is just one possible application of
FDA's new authorities in the Federal Food, Drug, and Cosmetic Act (FD&C
Act) section 505-1(e)(4) (21 U.S.C. 355-1(e)(4)) related to packaging
and disposal. We are considering, and invite comment on, other possible
applications of these authorities, including novel packaging or other
safe disposal options that would meet the SUPPORT Act standards.
Furthermore, we actively encourage drug manufacturers and others to
innovate in this space. We believe that the potential disposal
requirement outlined below would provide patients and caregivers with a
convenient additional option that would complement existing disposal
options (e.g., take-back days, kiosks, flushing, and in-home disposal
products). This potential requirement could be a significant and
readily achievable step toward improving the safe use of opioid
analgesics.
FDA is establishing this docket to solicit input from stakeholders
on all aspects of this potential requirement under the OA REMS,
including comments on specific questions posed in section III of this
notice.
II. Mail-Back Envelopes Dispensed With Opioid Analgesics in an
Outpatient Setting
In this section, we identify available data showing that many
patients do not use all of their prescribed opioid analgesics. This
well-documented outcome results in unused opioid analgesics that, if
not securely stored, may be easily accessible and subject to nonmedical
use, accidental exposure, and overdose. We summarize published
literature regarding the potential impacts of in-home disposal options
and whether they could increase disposal of unused opioid analgesics,
especially when coupled with patient education on the importance of
disposal. We then describe existing disposal options and programs,
including take-back days, collection kiosks in pharmacies and other
locations, flushing, in-home disposal, and mail-back envelopes. We also
describe a potential requirement, as part of the OA REMS, that mail-
back envelopes and education on safe disposal be provided with opioid
analgesics dispensed in an outpatient setting.
A. Unused, Improperly Stored Opioids Provide an Easily Accessible
Supply of Opioids for Nonmedical Use, Accidental Exposure, and Overdose
Many patients report having excess opioid analgesic tablets from
prescriptions they received after surgical procedures. A systematic
review from 2017 reported that after seven common surgical procedures,
67 to 92 percent of patients had excess opioid analgesics (Ref. 11). A
more recent systematic review that included articles published up to
2019 determined that, in studies of patient-reported use of opioid
analgesics after surgical procedures that reported on unused tablets,
most studies reported that 50 to 70 percent of tablets went unused
(Ref. 10). Articles published since the last systematic review continue
to report excess tablets after treatment of acute pain from surgical
procedures or from treatment in emergency departments (Refs. 12 to 21).
Patients who are prescribed opioid analgesics to treat chronic pain
may also have unused opioids requiring disposal, for example, when
changing opioid therapy (new opioid ingredient or tablet strength),
upon discontinuation of opioid therapy, or upon death. Removing unused
opioids from a home is an important public health intervention as many
studies report that patients frequently store opioid analgesic tablets
in unsecure locations (Ref. 10), making them easily accessible for
nonmedical use, accidental exposure, and overdose.
B. Provision of Education and In-Home Disposal Options May Increase
Disposal of Unused Opioid Analgesics
Educating patients about opioid analgesic disposal options may
increase the disposal rate \2\ for unused opioids (Ref. 20). In a
recent review of the literature examining opioid disposal options and
practices, most studies found that fewer than 50 percent of patients
disposed of their opioids (Ref. 20). The majority of studies that
examined the effect of providing patient education on the rate of
disposing of unused postoperative opioids found that patient education
increased the disposal rate by 15 to 30 percent compared to patients
who did not receive any additional education. Two investigations found
that text message reminders also increased the disposal rate by
approximately 30 percent in the text message reminder group compared to
patients who did not receive reminders (Refs. 21 and 22).
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\2\ The percent of patients who dispose of unused medications.
This document specifically discusses disposal of opioid analgesic
medications.
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There is also limited evidence that providing a disposal option
along with education increased the probability of disposal over that of
providing education alone. For example, one study assessed the
difference in postoperative disposal rates when patients were
[[Page 23871]]
provided a take-home disposal method, patient education, or both (Ref.
23). Compared to usual care, either patient education or providing a
take-home disposal method increased the disposal rate approximately 12
percent; for the group of patients who received both education and a
take-home disposal method, the disposal rate increased by 19.5 percent.
The four studies where a disposal kit was provided uniformly reported
an increase in actual or planned disposal rates, and in three of four
studies, the rates increased to over 50 percent of the study population
(Refs. 23 to 26).
While disposal products provided to patients in these studies were
often not specified, and the study populations usually received them
after hospital encounters for surgical procedures, it is reasonable to
assume that similar increases in disposal rates may also occur with
mail-back envelopes and for other situations outside of post-surgical
pain. What is less clear is whether education provided in a retail
pharmacy setting will be as successful as the patient education
provided in a post-surgical setting. We are interested in descriptions
of programs that provide mail-back envelopes specifically, as well as
those in which patient counseling on disposal is provided at retail
pharmacies. In addition to program descriptions, we are interested in
data on the effectiveness of mail-back envelope provision and
counseling on disposal provided at retail pharmacies in increasing
opioid analgesic disposal rates.
C. New REMS Authority Over Drug Disposal and Packaging
Section 3032 of the SUPPORT Act amended FDA's REMS authority.
Specifically, as a part of a REMS, FDA may require that a drug for
which there is a serious risk of an adverse event occurring from abuse
or overdose be dispensed to certain patients with safe disposal
packaging or a safe disposal system for purposes of rendering the drug
``nonretrievable'' (as that term is defined in a regulation adopted by
the Drug Enforcement Administration (DEA)), if FDA determines that such
safe disposal packaging or system may mitigate such serious risk and is
sufficiently available (see section 505-1(e)(4) of the FD&C Act). Under
DEA regulations (21 CFR 1317.90(a)), the requirement to render
controlled substances ``non-retrievable'' applies only to DEA
registrants and does not apply to ultimate users or patients.\3\
However, in the SUPPORT Act, Congress made the ``nonretrievable''
standard applicable to any safe disposal packaging or system FDA may
require under a REMS (see 21 U.S.C. 355-1(e)(4)). FDA may also require
that a drug for which there is such serious risk be made available for
dispensing to certain patients in unit-dose packaging, packaging that
provides a set duration, or another packaging system that FDA
determines may mitigate that risk (21 U.S.C. 355-1(e)(4)).
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\3\ 79 FR 53520 at 53541, September 9, 2014.
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A packaging or disposal requirement under this provision can be
imposed for prescription drugs that are the subject of applications
approved under section 505(c) of the FD&C Act (21 U.S.C. 355(c)) or
section 351 of the Public Health Service Act, as well as drugs that are
the subject of abbreviated new drug applications (ANDAs) approved under
section 505(j) of the FD&C Act if a packaging or disposal requirement
is required for the applicable reference listed drug (see section 505-
1(i)(1)(B) of the FD&C Act). FDA can permit packaging systems and safe
disposal packaging or safe disposal systems for drugs that are the
subject of ANDAs that are different from those required for the
applicable reference listed drugs (see section 505-1(i)(2)(B) of the
FD&C Act). FDA must take into consideration the burden on patients'
access to the drug and the burden on the healthcare delivery system
that would be associated with any such packaging or disposal
requirement, and must consult with other relevant Federal Agencies with
authorities over drug disposal packaging in certain circumstances (see
section 505-1(e)(4) of the FD&C Act).
The DEA has defined ``non-retrievable'' through regulation (21 CFR
1300.05(b)). It means, in part, ``the condition or state to which a
controlled substance shall be rendered following a process that
permanently alters that controlled substance's physical or chemical
condition or state through irreversible means and thereby renders the
controlled substance unavailable and unusable for all practical
purposes.'' The regulation further provides that ``a controlled
substance is considered non-retrievable when it cannot be transformed
to a physical or chemical condition or state as a controlled substance
or controlled substance analogue,'' and that ``the purpose of
destruction is to render the controlled substance(s) to a non-
retrievable state and thus prevent diversion of any such substance to
illicit purposes'' (21 CFR 1300.05(b)).
Under DEA regulations, an entity registered with the DEA \4\ may
collect controlled substances from ultimate users, to include
collection by mail-back packages or envelopes, for the purpose of
destruction.\5\ To be considered ``destroyed,'' a mail-back package
must be destroyed in compliance with applicable Federal, State, tribal,
and local laws and regulations and must be rendered non-retrievable.\6\
Mail-back envelopes dispensed with opioid analgesics pursuant to a
mail-back program that operates in compliance with DEA regulations and
all other applicable laws would be ``for the purposes of rendering the
drug nonretrievable,'' as required by section 505-1(e)(4) of the FD&C
Act. There are multiple companies that operate DEA-registered mail-back
programs and have mail-back envelopes commercially available, which
could be utilized by drug manufacturers who would be subject to the
potential REMS requirement described in this notice.
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\4\ Manufacturers, distributors, reverse distributors, narcotic
treatment programs, hospitals/clinics with an onsite pharmacy, and
retail pharmacies that desire to be collectors shall modify their
registration to obtain authorization to be a collector (21 CFR
1317.40(a); 1301.51). A collector would need to submit a letter of
request for modification of their registration to the Registration
Unit at the DEA and include the registrant's name, address,
registration number, and the type of collection (e.g., a mail-back
program and/or a collection receptacle) that the collector intends
to conduct.
\5\ DEA regulations address take-back events, mail-back
programs, and collection receptacles (21 CFR 1317.65, 1317.70, and
1317.75, respectively).
\6\ 21 CFR 1317.90(a).
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D. Mail-Back Envelopes in the Current Landscape of Opioid Disposal
Options
There are various options for safely disposing of opioid analgesics
available to patients, all of which can achieve the goal of removing
the risks associated with having unused and unsecured opioids stored in
the home. There are both in-home disposal options (e.g., flushing,
commercially available in-home disposal products) and disposal options
outside of the home (i.e., collection kiosks, take-back events). FDA
currently recommends disposing of opioids in permanent collection sites
(e.g., kiosks in pharmacies) or at take-back events (Ref. 27). If these
disposal options are not readily available, FDA recommends either
flushing (for opioids on FDA's ``Flush List'' (Ref. 28) or mixing with
an unpalatable substance and disposing in household trash (Ref. 27).
However, each option has its own challenges, which can result in
individuals being unable, unwilling, or reluctant to use them. For
example, collection sites (e.g., kiosks) require
[[Page 23872]]
individuals to bring opioid analgesics out of the home to a public
place, either a pharmacy or law enforcement facility. This requires
planning, access to transportation, and follow-through. Some
individuals are unable to readily or easily travel to a collection
site. In addition, some individuals may be reluctant to bring opioid
analgesics to a public location due to social stigma, or may fear
entering law enforcement locations, especially while carrying opioid
analgesics.
In-home disposal options also have challenges. Many patients are
reluctant to flush opioids (or other medications) due to environmental
concerns (Ref. 28). FDA's recommendation to mix some opioids (i.e.,
those not on the ``flush list'') with an unpalatable substance and
dispose in household trash is a multistep process some patients may be
unwilling or reluctant to undertake. In addition, disposal of opioids
in household trash may not prevent all accidental exposures.
Commercially available in-home disposal products (e.g., DisposeRx
packets or Deterra kits) commonly dispensed by some pharmacies are
another option, but they also require multiple steps (e.g., emptying
pills from one container into another container, adding water, shaking
to mix contents, disposing in household trash) (Refs. 29 to 31), and
some individuals may be reluctant to use them due to environmental
concerns. Further, FDA's understanding is that these products may not
render drugs ``nonretrievable'' within the meaning of the DEA
regulation referenced in section 505-1(e)(4)(B). Mail-back envelopes
require individuals to put the mail-back envelopes in a mailbox, which,
for some individuals, may be physically distanced from their home
(e.g., apartments, P.O. boxes, Native American reservations).
Additionally, patients may be reluctant to put opioids in the mail for
fear of diversion (Ref. 32). Some individuals may be more inclined to
use one option; others a different option. Accordingly, FDA believes it
is important to provide patients with a range of reasonable options,
and to provide appropriate education on each of these options.
FDA is aware that many organizations, both public and private, have
ongoing efforts to increase safe disposal of unused opioids. For
example, large retail pharmacy chains and many independent pharmacies
operate drug disposal programs that include making drug disposal kiosks
available in pharmacies, sponsoring drug ``take-back'' days and
providing in-home disposal products (Refs. 33 to 37). It is our
understanding that pharmacists often are instructed to counsel patients
and include educational materials about safe disposal in conjunction
with providing in-home disposal products. Some States and
municipalities have passed legislation requiring manufacturers who sell
drugs in their jurisdictions to fund drug disposal programs that can
include subsidizing kiosks in pharmacies and/or the provision of in-
home disposal products, including, occasionally, mail-back envelopes
(Refs. 38 to 40).
The Agency believes it is important for patients to have multiple
options for disposing of unused opioids, including kiosks, take-back
events, and in-home disposal options. Mail-back envelopes are one
option that has multiple favorable characteristics. They do not require
patients to mix medications with water, chemicals, or other substances.
Mail-back envelopes are also required to be postage paid,\7\ thereby
providing patients with a free disposal option. Further, most patients
can mail these envelopes from their home. Additionally, the DEA and the
U.S. Postal Service (USPS) have regulations and policies to ensure that
mail-back envelopes are fit for purpose.\8\ The USPS has longstanding
policies in place to safely and securely transport mail-back envelopes
to the location where they will be destroyed.\9\ Finally, unlike other
alternatives described here, the DEA requires mail-back envelopes to be
disposed of in a manner that renders them non-retrievable,\10\ which is
typically accomplished through incineration. As a result, mail-back
envelopes (along with collection kiosks) result in less opioids in the
water supply and landfills than is associated with other disposal
options.
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\7\ 21 CFR 1317.70(c)(4). DEA added this requirement because it
believed that ``pre-paid postage will ensure that the package is not
returned to sender, which will help reduce its handling and
therefore, the diversion risks'' (79 FR 53520 at 53536, September 9,
2014).
\8\ See 21 CFR 1317.70; USPS Publication 52, Mail-back programs.
\9\ Mail-back collectors are required to provide mail recipients
with readymade packaging and labels that comply with USPS
regulations for mailing controlled substances, including unique
Intelligent Mail package barcodes. See USPS Publication 52, Mail-
back programs.
\10\ See 21 CFR 1317.70(a); 1317.90(a).
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FDA recognizes that, notwithstanding these benefits, mail-back
envelopes are, at present, relatively underutilized. Large retail
pharmacy chains have focused on take-back days, kiosks, and a provision
of commercially available in-home disposal products (Refs. 33 to 37),
while it appears manufacturers subject to State-mandated disposal
requirements have primarily focused on collection kiosks. FDA
anticipates that a REMS-mandated disposal program for opioid analgesics
focused on provision of mail-back envelopes, together with education on
multiple safe disposal options, could complement these existing opioid
disposal programs.
E. Approach Under Consideration: Mail-Back Envelopes and Education on
Proper Disposal Must Be Provided to Patients With Opioid Analgesics
Dispensed in Outpatient Pharmacies
FDA is considering adding a mail-back envelope requirement to the
OA REMS to require that all opioid analgesics, including immediate-
release (IR), extended-release (ER), and long-acting (LA) formulations,
used in the outpatient setting that are subject to the OA REMS be
dispensed with mail-back envelopes.
Although most studies reported excess opioid analgesics after a
surgical procedure (Refs. 10 and 11), suggesting the need to target
disposal options for patients with acute pain, the pharmacist at the
time of dispensing may find it difficult to differentiate whether a
patient is being treated for acute or chronic pain. For example, using
specific formulations of opioid analgesics as a proxy for
distinguishing between acute or chronic pain would not be appropriate
because patients with chronic pain may take both IR and ER or LA
formulations. In fact, most patients receiving an opioid analgesic,
regardless for how long, use IR formulations (Ref. 41). Further, as
mentioned above, opioid analgesics prescribed for chronic pain can also
become unneeded. Therefore, FDA is considering having any mail-back
envelope requirement apply to all opioid analgesics, including IR, ER,
and LA formulations, used in the outpatient setting for acute or
chronic pain that are subject to the OA REMS.
That said, requiring that a mail-back envelope be dispensed with
every opioid analgesic prescription could be inefficient and lead to an
excess of dispensed mail-back envelopes. The use of algorithms to
target mail-back envelope distribution in a thoughtful, tailored manner
would be expected to positively impact program fidelity and outcomes
and decrease waste. Some existing retail pharmacy programs that provide
disposal options to patients use algorithms to target disposal options
to certain patients or certain circumstances, such as only providing
disposal options every 6 months to patients who continue to fill
multiple opioid analgesic prescriptions (Refs. 33 and 34). Other
potential algorithms
[[Page 23873]]
could target the provision of mail-back envelopes to patients filling a
prescription for an amount of opioids generally consistent with acute
pain treatment, or to patients with a change in dose of a recurring
opioid analgesic prescription who may then have unused opioids. FDA
recognizes that the upfront effort to implement algorithms could be
complicated but expects that the use of algorithms would be more
efficient and would reduce the long-term burden on the healthcare
delivery system by targeting the distribution of mail-back envelopes to
patients most likely to have unused opioids. FDA would appreciate input
on appropriate optimal algorithm design for a potential targeted mail-
back envelope provision. We would also expect, regardless of the
algorithm used, that mail-back envelopes would be provided to any
patient or caregiver who requests one. Additionally, we would expect
that if a given patient does not want the mail-back envelope, they
could decline the offer.
Multiple studies we reviewed indicated that unused opioids are
often stored in unsecure locations (Ref. 10) and that patients were
reluctant to dispose of unused opioid analgesics for various reasons,
including the patient's belief that they might need the unused opioids
in the future (Refs. 32, 42, and 43). In the studies that we reviewed,
patient and caregiver education about disposal was often provided with
an at-home disposal option during counseling about care after a
procedure, and patients were reminded about disposal during followup
contacts. For example, one study found that combining an in-home
disposal option with patient education focused on the importance of
disposal increased the disposal rate versus simply providing an in-home
disposal option or patient education (Ref. 23). Accordingly, we believe
that patient and caregiver education that explains the importance of
safe storage and proper disposal and addresses patients' reluctance to
dispose of opioids would be an integral component of any mail-back
envelope REMS requirement. We also believe that take-home educational
materials on proper disposal, as well as followup reminders (e.g.,
automated text messages), are likely to have a positive reinforcing
effect on patient counseling provided by the pharmacist at the time of
dispensing.
There are multiple ways a mail-back envelope REMS requirement could
be designed and operationalized. We describe two possibilities here,
and welcome input on others. One option would be to require that drug
manufacturers subject to the OA REMS make mail-back envelopes available
to outpatient pharmacies at no cost and allow pharmacies to provide
mail-back envelopes and counseling on disposal according to their own
policies and procedures. Additionally, to encourage patient education,
FDA may also require manufacturers to create educational materials to
assist pharmacists in counseling patients on safe storage and proper
disposal. However, this option would not require that pharmacies
actually provide mail-back envelopes, counseling on disposal, or take-
home educational materials. As such, this option would ultimately rely
on pharmacy policies and procedures to drive the use of mail-back
envelopes and counseling on safe disposal.
Alternatively, FDA could require manufacturers to only distribute
opioids to outpatient pharmacies certified in the REMS. Certification
could require that mail-back envelopes, patient counseling, take-home
materials, and followup reminders (e.g., text messages) be provided
according to the terms of the REMS, and that all of these activities be
conducted and appropriately documented. Again, manufacturers would
supply mail-back envelopes to pharmacies at no cost. Certification of
pharmacies could include requiring pharmacy staff to complete specified
training on how to counsel patients on safe storage and proper
disposal. As with the first option, FDA may also require manufacturers
to create educational materials to assist pharmacies with patient
counseling.
For any mail-back envelope REMS requirement, FDA would intend for
the program to increase the quantity of unused opioids properly
disposed of, and, therefore, to decrease the quantity of unused opioids
available for nonmedical use, accidental exposure, and overdose. FDA
anticipates the potential for greater impact with the second option
than the first but acknowledges that the second option would impose
greater burdens on the healthcare system.
The potential burdens associated with a mail-back envelope REMS
requirement on pharmacies and pharmacists would include, depending on
the program design: (1) Completion of any REMS-mandated training and
certification; (2) implementation of REMS-compliant processes in
pharmacies; and (3) documentation of compliance with REMS requirements
by pharmacies. These efforts are in addition to existing State and
Federal pharmacy requirements associated with dispensing opioids (e.g.,
checking prescription drug monitoring programs). A mail-back envelope
REMS requirement is likely to be more effective under the second
scenario described above. However, the more requirements the REMS
imposes, the more likely that relevant stakeholders, particularly
pharmacies, will have challenges complying with the requirements.
Ensuring the requirements are met may necessitate remediation steps,
such as reeducation, or even decertification, if a pharmacy fails to
comply. Declining to certify or decertifying a pharmacy could affect
patients' access to appropriately prescribed opioid analgesics.
Accordingly, the ability of potential OA REMS disposal requirements
to be integrated into healthcare providers' existing workflow is an
important consideration in FDA's decision making. The Agency is seeking
input on the design of a potential mail-back envelope REMS requirement
that strikes the right balance between positive impact on unused opioid
analgesic disposal and burden on pharmacies and other stakeholders.
F. Other Considerations for Requiring Provision of Mail-Back Envelopes
With Opioid Analgesics
Current DEA and USPS regulations and policies require mail-back
envelopes to be nondescript, i.e., they must not include any markings
or other information that might indicate that the package contains
controlled substances.\11\ These specifications help alleviate concerns
that mail-back envelopes can easily be identified for diversion while
in transit. However, if a potential mail-back envelope REMS requirement
were implemented, it could be expected to greatly increase the number
of mail-back envelopes in circulation. The USPS has informed the Agency
that the existing regulatory scheme, as well as USPS' rigorous
monitoring and policing mechanisms, should be adequate to accommodate
an increase in mail-back envelope utilization. We welcome other
stakeholder views on this issue, including how any potential adverse
consequences could be mitigated.
---------------------------------------------------------------------------
\11\ 21 CFR 1317.70(c)(1); USPS Publication 52, Mail-back
programs.
---------------------------------------------------------------------------
FDA expects that a mail-back envelope OA REMS requirement would
provide patients with an additional disposal option that complements
disposal options already available through ongoing public and private
efforts. The Agency understands mail-back envelopes will not be the
preferred disposal option for all patients. FDA's expectation is that
existing disposal
[[Page 23874]]
programs (e.g., provision of in-home disposal options by many
pharmacies, including most major chain pharmacies) will continue, such
that a mail-back envelope mandate would provide patients with an
additional disposal option without affecting other existing disposal
options. We are seeking input on how a mail-back envelope OA REMS
requirement could be designed and operationalized to complement
existing disposal efforts and programs.
G. Other Actions That Could Complement a Mail-Back Envelope REMS
Mandate
FDA is considering additional actions that may be necessary or
appropriate if we were to impose a mail-back envelope disposal
requirement under the OA REMS. For example, FDA would need to amend
recommendations in the ``Remove the Risk'' campaign on safe disposal of
opioids to include information on the availability and use of mail-back
envelopes (Ref. 44). Likewise, FDA would need to amend the information
on disposal in FDA-approved prescriber and patient labeling for opioids
that would be subject to the mail-back envelope REMS requirement, as
this labeling currently does not mention mail-back envelopes. FDA is
also considering whether it might be appropriate to have a large media
campaign aimed at increasing public awareness of the importance of
promptly disposing unused opioids and how to safely dispose of them.
FDA welcomes input on these and any other potential actions that could
increase the effectiveness of a mail-back envelope disposal requirement
under the OA REMS.
III. Additional Request for Comments And Information
FDA is soliciting comments from stakeholders regarding all aspects
of the potential mail-back envelope REMS mandate described in this
document. The Agency is particularly interested in comments on the
following topics:
1. The potential safety advantages and public health impacts of
providing mail-back envelopes with opioid analgesics dispensed in an
outpatient setting.
2. Whether there are specific opioid analgesic drug products for
which requiring mail-back envelopes is more important from a public
health perspective and, if so, which products.
3. How pharmacies could identify those patients who are most likely
to have unused opioids to optimize provision of mail-back envelopes to
these patients and potentially positively impact the share of mail-back
envelopes that are utilized to safely dispose of opioid analgesics.
4. How pharmacies could develop and implement algorithms to
determine when to provide a mail-back envelope, including how feasible
or practical it would be for pharmacies to do so.
5. Whether requiring provision of mail-back envelopes under the OA
REMS should also include a requirement for patient counseling and/or
provision of take-home materials on safe disposal at the point of
dispensing.
6. What key educational messages regarding secure storage and safe
disposal should be included in any patient education component of the
potential OA REMS requirement described in this notice, including
educational messages to increase uptake and use of mail-back envelopes,
as well as what form that education should take (e.g., handouts,
pharmacist counseling of patients).
7. How a mail-back envelope requirement could be designed and
implemented to help ensure that the disposal requirement minimizes
burden on pharmacies while still providing the public health benefit.
As discussed in the document, there is a tradeoff between the potential
effectiveness of a mail-back envelope REMS requirement and the level of
burden imposed on those pharmacies involved in implementing the
requirement.
8. Possible challenges, including technical and logistical
challenges, with the potential REMS mandate described in this notice,
and what factors could impact manufacturers' ability to provide mail-
back envelopes to pharmacies, or the ability of pharmacies to dispense
mail-back envelopes and provide appropriate disposal education to
consumers.
9. The impact of a mail-back envelope REMS requirement on other
stakeholders, including manufacturers, prescribers, payers, and
patients.
10. How a mail-back envelope REMS requirement could be designed and
operationalized to provide another option for patients that would
complement current pharmacy disposal programs, policies, and
procedures, as well as Federal, State, local, and private sector
efforts on proper opioid disposal.
11. Possible negative impacts of a potential mail-back envelope
REMS mandate, including whether there is a risk that it could diminish
the impact of other public and private efforts around safe disposal.
For example, could it be the case that for some patients, provision of
a mail-back envelope together with another commercially available in-
home disposal product, and education on how to use both, could be
overwhelming and lead to less comprehension and utilization of either
option?
12. How manufacturers and FDA could best assess the effectiveness
of a mail-back envelope OA REMS requirement. Assessing the impact of a
mail-back envelope requirement in a REMS is likely to be challenging
because, among other reasons, current DEA regulations prohibit mail-
back envelopes from being opened prior to destruction, preventing a
direct inventory of contents; and some of the opioids disposed of in
mail-back envelopes would presumably be disposed of using another
disposal option if the mail-back envelope were not provided.
13. How patients and others may perceive the environmental impact
of a potential mail-back envelope requirement, including the potential
for such envelopes to reduce the amount of medications flushed or
disposed of in landfills.
14. Any existing programs that provide mail-back envelopes,
especially programs that provide patient counseling on disposal and
that operate in retail pharmacies, including any data on the
effectiveness of these programs.
15. Section 3032 of the SUPPORT Act authorizes the Agency to use
its REMS authority to require that a safe disposal packaging or safe
disposal system for the purposes of rendering the drug nonretrievable
be dispensed to certain patients with drugs that pose a serious risk of
abuse or overdose if, among other things, FDA determines that such safe
disposal packaging or system may mitigate such risks and is
sufficiently available (21 U.S.C. 355-1(e)(4)). We recognize that the
approach described in this document is only one potential use of the
Agency's REMS authority concerning disposal. Comment on other possible
uses of the Agency's REMS authority concerning disposal, including
providing any data or information about whether other disposal
packaging or disposal systems we might consider mandating, such as
commercially available in-home disposal products, would satisfy the
statutory requirements at 21 U.S.C. 355-1(e)(4).
16. Discuss other actions FDA could take in addition to, and in
support of, a mail-back envelope disposal REMS requirement to increase
safe disposal of unused opioid analgesics.
IV. References
The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and available for
viewing by
[[Page 23875]]
interested persons between 9 a.m. and 4 p.m., Monday through Friday;
they also are available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
References without asterisks are not on public display at <a href="https://www.regulations.gov">https://www.regulations.gov</a> because they have copyright restriction. Some
references may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. FDA has verified the web addresses, as of the
date this document publishes in the Federal Register, but websites are
subject to change over time.
1. * U.S. Department of Health and Human Services. Substance Abuse
and Mental Health Services Administration. ``Key Substance Use and
Mental Health Indicators in the United States: Results from the 2019
National Survey on Drug Use and Health.'' HHS Publication No. PEP20-
07-01-001, NSDUH Series H-55, Rockville, MD: Center for Behavioral
Health Statistics and Quality, Substance Abuse and Mental Health
Services Administration (2020). Available at: <a href="https://www.samhsa.gov/data/sites/default/files/reports/rpt29393/2019NSDUHFFRPDFWHTML/2019NSDUHFFR090120.htm">https://www.samhsa.gov/data/sites/default/files/reports/rpt29393/2019NSDUHFFRPDFWHTML/2019NSDUHFFR090120.htm</a>.
2. Carlson, R.G., R.W. Nahhas, S.S. Martins, et al. ``Predictors of
Transition to Heroin Use Among Initially Non-Opioid Dependent
Illicit Pharmaceutical Opioid Users: A Natural History Study.'' Drug
and Alcohol Dependence, Vol. 160 (March 2016): 127-134.
3. Harocopos, A., B. Allen, and D. Paone. ``Circumstances and
Contexts of Heroin Initiation Following Non-Medical Opioid Analgesic
Use in New York City.'' International Journal of Drug Policy, Vol.
28 (February 2016): 106-112.
4. Surratt, H.L., S.P. Kurtz, M. Buttram, et al. ``Heroin Use Onset
Among Nonmedical Prescription Opioid Users in the Club Scene.'' Drug
and Alcohol Dependence, Vol. 179 (October 2017): 131-138.
5. Lankenau, SE, M. Teti, K. Silva, et al. ``Initiation Into
Prescription Opioid Misuse Amongst Young Injection Drug Users.''
International Journal of Drug Policy, Vol. 23(1) (January 2012): 37-
44. <a href="https://doi.org/10.1016/j.drugpo.2011.05.014">https://doi.org/10.1016/j.drugpo.2011.05.014</a>.
6. Wang, G.S., H. Olsen, G. Severtson, et al. ``The Impact of the
Prescription Opioid Epidemic on Young Children: Trends and
Mortality.'' Drug and Alcohol Dependence, Vol. 211 (June 2020):
107924. <a href="https://doi.org/10.1016/j.drugalcdep.2020.107924">https://doi.org/10.1016/j.drugalcdep.2020.107924</a>.
7. IQVIA. National Prescription Audit<SUP>TM</SUP>. Data extracted
January 14, 2022.
8. * Ahmad, F.B., L.M. Rossen, and P. Sutton. ``Provisional Drug
Overdose Death Counts.'' National Center for Health Statistics
(2021). <a href="https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm">https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm</a>.
Accessed August 20, 2021.
9. * National Institute on Drug Abuse. ``Overdose Death Rates.''
January 20, 2022. <a href="https://www.drugabuse.gov/drug-topics/trends-statistics/overdose-death-rates">https://www.drugabuse.gov/drug-topics/trends-statistics/overdose-death-rates</a>.
10. Mallama, C.A., C. Greene, A.A. Alexandridis, et al. ``Patient-
Reported Opioid Analgesic Use After Discharge From Surgical
Procedures: A Systematic Review.'' Pain Medicine, Vol. 23(1)
(January 2022): 22-29. <a href="https://doi.org/10.1093/pm/pnab244">https://doi.org/10.1093/pm/pnab244</a>.
11. Bicket, M.C., J.J. Long, P.J. Pronovost, et al. ``Prescription
Opioid Analgesics Commonly Unused After Surgery: A Systematic
Review.'' JAMA Surgery, Vol. 152(11) (November 2017): 1066-1071.
<a href="https://doi.org/10.1001/jamasurg.2017.0831">https://doi.org/10.1001/jamasurg.2017.0831</a>.
12. Atwood, K., T. Shackleford, W. Lemons, et al. ``Postdischarge
Opioid Use After Total Hip and Total Knee Arthroplasty.''
Arthroplasty Today, Vol. 7 (February 2021): 126-129. <a href="https://doi.org/10.1016/j.artd.2020.12.021">https://doi.org/10.1016/j.artd.2020.12.021</a>.
13. McCarthy, D.M., H.S. Kim, S.I. Hur, et al. ``Patient-Reported
Opioid Pill Consumption After an ED Visit: How Many Pills Are People
Using?'' Pain Medicine, Vol. 22(2) (February 2021): 292-302. <a href="https://doi.org/10.1093/pm/pnaa048">https://doi.org/10.1093/pm/pnaa048</a>.
14. Patel, M.S., G.F. Updegrove, A.M. Singh, et al. ``Characterizing
Opioid Consumption in the 30-Day Post-Operative Period Following
Shoulder Surgery: Are We Over Prescribing?'' The Physician and
Sportsmedicine, Vol. 49(2) (May 2021): 158-164. <a href="https://doi.org/10.1080/00913847.2020.1789439">https://doi.org/10.1080/00913847.2020.1789439</a>.
15. Pruitt, L.C.C., G.C. Casazza, C.I. Newberry, et al. ``Opioid
Prescribing and Use in Ambulatory Otolaryngology.'' The
Laryngoscope, Vol. 130(8) (August 2020): 1913-1921. <a href="https://doi.org/10.1002/lary.28359">https://doi.org/10.1002/lary.28359</a>.
16. Stepan, J.G., H.A. Sacks, C.I. Verret, et al. ``Standardized
Perioperative Patient Education Decreases Opioid Use After Hand
Surgery: A Randomized Controlled Trial.'' Plastic and Reconstructive
Surgery, Vol. 147(2) (February 2021): 409-418. <a href="https://doi.org/10.1097/PRS.0000000000007574">https://doi.org/10.1097/PRS.0000000000007574</a>.
17. Stone, A.L., D. Qu'd, T. Luckett, et al. ``Leftover Opioid
Analgesics and Disposal Following Ambulatory Pediatric Surgeries in
the Context of a Restrictive Opioid-Prescribing Policy.'' Anesthesia
& Analgesia (January 2022). Vol. 134: 133-140. <a href="https://doi.org/10.1213/ANE.0000000000005503">https://doi.org/10.1213/ANE.0000000000005503</a>.
18. Wyles, C.C., C.A. Thiels, M. Hevesi, et al. ``Patient Opioid
Requirements Are Often Far Less Than Their Discharge Prescription
After Orthopaedic Surgery: The Results of a Prospective Multicenter
Survey.'' Journal of the American Academy of Orthopaedic Surgeons,
Vol. 29(7) (April 2021): e345-e353. <a href="https://doi.org/10.5435/JAAOS-D-19-00415">https://doi.org/10.5435/JAAOS-D-19-00415</a>.
19. Agarwal, A.K., D. Lee, Z. Ali, et al. ``Patient-Reported Opioid
Consumption and Pain Intensity After Common Orthopedic and Urologic
Surgical Procedures With Use of an Automated Text Messaging
System.'' JAMA Network Open, Vol. 4(3) (March 2021): e213243.
<a href="https://doi.org/10.1001/jamanetworkopen.2021.3243">https://doi.org/10.1001/jamanetworkopen.2021.3243</a>.
20. * Kornegay, C. ``Epidemiology Review: Consumer Opioid Disposal
Literature Scan and Search Results.'' AIMS 2021-775. Uploaded to
DARRTS April 29, 2021.
21. McCarthy, D.M., L. Curtis, D.M. Courtney, et al. ``Improving
Patient Knowledge of Opioids: Results of the Emergency Department
Electronic Medication Complete Communication Trial for Opioids.''
Academic Emergency Medicine, Vol. 26 (April 2019): S133. <a href="https://doi.org/10.1111/acem.13756">https://doi.org/10.1111/acem.13756</a>.
22. Nahhas, C.R., C.P. Hannon, J. Yang, et al. ``Education Increases
Disposal of Unused Opioids After Total Joint Arthroplasty: A
Cluster-Randomized Controlled Trial.'' The Journal of Bone and Joint
Surgery, Vol. 102 (June 2020): 953-960. <a href="https://doi.org/10.2106/jbjs.19.01166">https://doi.org/10.2106/jbjs.19.01166</a>.
23. Voepel-Lewis, T., F.A. Farley, J. Grant, et al. ``Behavioral
Intervention and Disposal of Leftover Opioids: A Randomized Trial.''
Pediatrics, Vol. 145(1) (January 2020): e20191431. <a href="https://doi.org/10.1542/peds.2019-1431">https://doi.org/10.1542/peds.2019-1431</a>.
24. Brummett, C.M., R. Steiger, M. Englesbe, et al. ``Effect of an
Activated Charcoal Bag on Disposal of Unused Opioids After an
Outpatient Surgical Procedure: A Randomized Clinical Trial.'' JAMA
Surgery, Vol. 154(6) (March 2019): 558-561. <a href="https://doi.org/10.1001/jamasurg.2019.0155">https://doi.org/10.1001/jamasurg.2019.0155</a>.
25. Stokes, S.M., R.Y. Kim, A. Jacobs, et al. ``Home Disposal Kits
for Leftover Opioid Medications After Surgery: Do They Work?''
Journal of Surgical Research, Vol. 245 (January 2020): 396-402.
<a href="https://doi.org/10.1016/j.jss.2019.07.034">https://doi.org/10.1016/j.jss.2019.07.034</a>.
26. Lawrence, A.E., A.J. Carsel, K.L. Leonhart, et al. ``Effect of
Drug Disposal Bag Provision on Proper Disposal of Unused Opioids by
Families of Pediatric Surgical Patients: A Randomized Clinical
Trial.'' JAMA Pediatrics, Vol. 173(8) (June 2019): e191695. <a href="https://doi.org/10.1001/jamapediatrics.2019.1695">https://doi.org/10.1001/jamapediatrics.2019.1695</a>.
27. * FDA. ``Disposal of Unused Medicines: What You Should Know.
Learn How to Dispose of Unused or Expired Drugs.'' <a href="https://www.fda.gov/drugs/safe-disposal-medicines/disposal-unused-medicines-what-you-should-know">https://www.fda.gov/drugs/safe-disposal-medicines/disposal-unused-medicines-what-you-should-know</a>. Accessed October 31, 2021.
28. * FDA. ``Drug Disposal: FDA's Flush List for Certain
Medicines.'' <a href="https://www.fda.gov/drugs/disposal-unused-medicines-what-you-should-know/drug-disposal-fdas-flush-list-certain-medicines">https://www.fda.gov/drugs/disposal-unused-medicines-what-you-should-know/drug-disposal-fdas-flush-list-certain-medicines</a>. Accessed October 31, 2021.
29. DisposeRx. ``Instructions for Disposal.'' <a href="https://disposerx.com/page/8/instuctions-for-disposal">https://disposerx.com/page/8/instuctions-for-disposal</a>. Accessed November 1, 2021.
30. Deterra. ``How it Works.'' <a href="https://deterrasystem.com/wp-content/uploads/2021/01/Deterra_HowToUse_English.pdf">https://deterrasystem.com/wp-content/uploads/2021/01/Deterra_HowToUse_English.pdf</a>. Accessed November 1,
2021.
31. Imarhia, F., T.J. Varisco, M.A. Wanat, et al. ``Prescription
Drug Disposal: Products Available for Home Use.'' Journal of the
American Pharmacists Association, Vol. 60 (July-August 2020): e7-
e13. https://
[[Page 23876]]
doi.org/10.1016/j.japh.2020.01.004.
32. Buffington, D.E., A. Lozicki, T. Alfieri, et al. ``Understanding
Factors That Contribute to the Disposal of Unused Opioid
Medication.'' Journal of Pain Research, Vol. 12 (February 2019):
725-732. <a href="https://doi.org/10.2147/jpr.s171742">https://doi.org/10.2147/jpr.s171742</a>.
33. Walmart. ``Stewardship.'' <a href="https://corporate.walmart.com/stewardship">https://corporate.walmart.com/stewardship</a>. Accessed October 31, 2021.
34. Rite Aid. ``Rite Aid Makes Free Opioid Disposal Solution
Available At More Than 2,500 Pharmacies Nationwide.'' <a href="https://www.businesswire.com/news/home/20180521005532/en/">https://www.businesswire.com/news/home/20180521005532/en/</a>. Accessed October
31, 2021.
35. CVS. ``CVS Pharmacy to Offer Safe Medication Disposal Chain-Wide
in 2020.'' <a href="https://cvshealth.com/news-and-insights/press-releases/cvs-pharmacy-to-offer-safe-medication-disposal-chain-wide-in-2020">https://cvshealth.com/news-and-insights/press-releases/cvs-pharmacy-to-offer-safe-medication-disposal-chain-wide-in-2020</a>.
Accessed November 1, 2021.
36. Walgreens. ``Safe Medication Disposal--Dispose of Unused
Medication.'' <a href="https://www.walgreens.com/topic/pharmacy/safe-medication-disposal.jsp">https://www.walgreens.com/topic/pharmacy/safe-medication-disposal.jsp</a>. Accessed November 1, 2021.
37. Kroger. ``National Drug Take-back Day'' <a href="https://www.kroger.com/health/pharmacy/prescriptions/takeback">https://www.kroger.com/health/pharmacy/prescriptions/takeback</a>. Accessed November 3, 2021.
38. Drug Take Back, Consolidated Laws of New York Chapter 45 Article
2-B, available at <a href="https://www.nysenate.gov/legislation/laws/PBH/A2-B">https://www.nysenate.gov/legislation/laws/PBH/A2-B</a>.
39. Drug Take-Back Program, Revised Code of Washington 69.48,
available at <a href="https://app.leg.wa.gov/rcw/default.aspx?cite=69.48">https://app.leg.wa.gov/rcw/default.aspx?cite=69.48</a>.
40. Pharmaceutical and Sharps Waste Stewardship Program, California
Code of Regulations Title 14, Chapter 11, Div. 7, Art. 4, available
at <a href="https://govt.westlaw.com/calregs/Browse/Home/California/CaliforniaCodeofRegulations?guid=I3A11525A8CDD4A6E87920BBB389851C4&originationContext=documenttoc&transitionType=Default&contextData=">https://govt.westlaw.com/calregs/Browse/Home/California/CaliforniaCodeofRegulations?guid=I3A11525A8CDD4A6E87920BBB389851C4&originationContext=documenttoc&transitionType=Default&contextData=</a>(sc.D
efault).
41. Hwang, C.S., E.M. Kang, Y. Ding, et al. ``Patterns of Immediate-
Release and Extended-Release Opioid Analgesic Use in the Management
of Chronic Pain, 2003-2014.'' JAMA Network Open, Vol. 1(2) (June
2018): e180216. <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2682877">https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2682877</a>.
42. Kennedy-Hendricks, A., A. Gielen, E. McDonald, et al.
``Medication Sharing, Storage, and Disposal Practices for Opioid
Medications Among US Adults.'' JAMA Internal Medicine, Vol. 176(7)
(July 2016): 1027-1029. <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2527388">https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2527388</a>.
43. Neill, L.A., H.S. Kim, K.A. Cameron, et al. ``Who Is Keeping
Their Unused Opioids and Why?'' Pain Medicine, Vol. 21(1) (January
2020): 84-91. <a href="https://academic.oup.com/painmedicine/article/21/1/84/5418890">https://academic.oup.com/painmedicine/article/21/1/84/5418890</a>.
44. * FDA. ``Safe Opioid Disposal--Remove the Risk Outreach
Toolkit.'' <a href="https://www.fda.gov/drugs/safe-disposal-medicines/safe-opioid-disposal-remove-risk-outreach-toolkit">https://www.fda.gov/drugs/safe-disposal-medicines/safe-opioid-disposal-remove-risk-outreach-toolkit</a>. Accessed November 23,
2021.
Dated: April 13, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-08372 Filed 4-20-22; 8:45 am]
BILLING CODE 4164-01-P
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