[Federal Register Volume 80, Number 158 (Monday, August 17, 2015)]
[Notices]
[Page 49244]
[FR Doc No: 2015-20229]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-0332]

Endotoxin Testing Recommendations for Single-Use Intraocular
Ophthalmic Devices; Guidance for Industry and Food and Drug
Administration Staff; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of the guidance entitled ``Endotoxin Testing
Recommendations for Single-Use Intraocular Ophthalmic Devices.''
National outbreaks of Toxic Anterior Segment Syndrome (TASS) have been
associated with single-use intraocular ophthalmic devices (IODs) and
single-use intraocular ophthalmic surgical instruments/accessories that
are contaminated with endotoxins. These devices can become contaminated
as part of the manufacturing, sterilization, or packaging processes.
This guidance document provides recommendations for endotoxin limits as
well as endotoxin testing to manufacturers and other entities involved
in submitting premarket applications (PMAs) or premarket notification
submissions (510(k)s) for different categories of IODs to mitigate
future outbreaks of TASS.

DATES: Submit either electronic or written comments on this guidance at
any time. General comments on Agency guidance documents are welcome at
any time.

ADDRESSES: An electronic copy of the guidance document is available for
download from the Internet. See the SUPPLEMENTARY INFORMATION section
for information on electronic access to the guidance. Submit written
requests for a single hard copy of the guidance document entitled
``Endotoxin Testing Recommendations for Single-Use Intraocular
Ophthalmic Devices'' to the Office of the Center Director, Guidance and
Policy Development, Center for Devices and Radiological Health, Food
and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 5431,
Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to
assist that office in processing your request.
    Submit electronic comments on the guidance 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 comments with the docket number
found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Michelle Tarver, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 2504, Silver Spring, MD 20993-0002, 301-
796-5620.

SUPPLEMENTARY INFORMATION:

I. Background

    TASS has been increasing in frequency over the past decade from
approximately 1 in 1,000 to about 2 in 100. Some cases of TASS are
severe enough to require secondary surgical interventions including
glaucoma surgery and corneal transplantation. The use of inadequately
or improperly processed ophthalmic surgical instruments is one of many
factors suggested as a potential cause of TASS. In many TASS cases,
bacterial endotoxin from medical devices is believed to cause the
inflammation.
    This guidance document was developed to notify manufacturers and
other entities involved in submitting PMAs or 510(k)s for different
categories of IODs of the recommended endotoxin limit for the release
of IODs and single-use intraocular ophthalmic surgical instruments/
accessories in an effort to mitigate future TASS outbreaks.
    The draft of this guidance was made available in the Federal
Register on April 17, 2014 (79 FR 21777), and the comment period closed
July 16, 2014. Only two sets of comments were received. The comments
were minor, and FDA made revisions to the document in response to the
comments where appropriate. FDA also removed posterior segment devices
from the scope of the guidance document. FDA may address endotoxin
testing recommendations for this device type in future guidance
documents.

II. Significance of Guidance

    This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on endotoxin testing and limits for single-use
IODs. It does not establish any rights for any person and is not
binding on FDA or the public. You can use an alternative approach if it
satisfies the requirements of the applicable statutes and regulations.

III. Electronic Access

    Persons interested in obtaining a copy of the guidance may do so by
downloading an electronic copy from the Internet. A search capability
for all Center for Devices and Radiological Health guidance documents
is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance
documents are also available at http://www.regulations.gov. Persons
unable to download an electronic copy of ``Endotoxin Testing
Recommendations for Single-Use Intraocular Ophthalmic Devices'' may
send an email request to<EMAIL_ADDRESS>to receive an
electronic copy of the document. Please use the document number 1836 to
identify the guidance you are requesting.

IV. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of
information found in FDA regulations. These collections of information
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The
collections of information in 21 CFR part 814 have been approved under
OMB control number 0910-0231.

V. 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. 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.

    Dated: August 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-20229 Filed 8-14-15; 8:45 am]
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[Federal Register Volume 79, Number 231 (Tuesday, December 2, 2014)]
[Proposed Rules]
[Pages 71364-71365]
[FR Doc No: 2014-28230]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 71

[Docket No. FAA-2013-0993; Airspace Docket No. 13-ASW-28]

Proposed Establishment of Class E Airspace; Tucumcari, NM

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of proposed rulemaking (NPRM), withdrawal.

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SUMMARY: This action withdraws the NPRM published in the Federal
Register on December 20, 2013. In that action, the FAA proposed to
establish Class E airspace at the Tucumcari VORTAC, Tucumcari, NM. The
FAA has determined that withdrawal of the NPRM is warranted as a result
of objections raised during the comment period.

DATES: As of December 2, 2014, the proposed rule published December 20,
2013, at 78 FR 77023, is withdrawn.

FOR FURTHER INFORMATION CONTACT: Raul Garza, Jr., Central Service
Center, Operations Support Group, Federal Aviation Administration,
Southwest Region, 2601 Meacham Blvd., Fort Worth, TX 76137; telephone:
817-321-7654.

SUPPLEMENTARY INFORMATION: On December 20, 2013, a NPRM was published
in the Federal Register (78 FR 77023) to amend Title 14 Code of Federal
Regulations (14 CFR) part 71 to establish Class E Airspace extending
upward from 1,200 feet above the surface at the Tucumcari VHF Omni-
Directional Radio Range Tactical Air Navigation Aid (VORTAC) Tucumcari,
NM, to contain aircraft while in Instrument Flight Rules conditions
under control of Albuquerque Air Route Traffic Control Center by
vectoring aircraft from en route airspace to terminal areas. As a
result of objections that were raised during the comment period, the
NPRM is being withdrawn. A new NPRM will be forthcoming.

List of Subjects in 14 CFR part 71

    Airspace, Incorporation by reference, Navigation (air).

The Withdrawal

    Accordingly, pursuant to the authority delegated to me, the Notice
of Proposed Rulemaking,, as published in the Federal Register of
December 20, 2013 (78 FR 77023) (FR Doc. 2013-30339), is hereby
withdrawn.

    Authority:  49 U.S.C. 106(g), 40103, 40113, 40120; E.O. 10854;
24 FR 9565, 3 CFR, 1959-1963 Comp., p. 389.

    Issued in Fort Worth, TX, on November 20, 2014.
Walter Tweedy,
Manager, Operations Support Group, ATO Central Service Center.
[FR Doc. 2014-28230 Filed 12-1-14; 8:45 am]
BILLING CODE 4910-14-P


[Federal Register Volume 79, Number 68 (Wednesday, April 9, 2014)]
[Notices]
[Pages 19619-19620]
[FR Doc No: 2014-07909]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-0233]

Center for Drug Evaluation and Research; Use of Innovative
Packaging, Storage, and/or Disposal Systems To Address the Misuse and
Abuse of Opioid Analgesics; Request for Comments; Establishment of a
Public Docket

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification; establishment of docket; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the
establishment of a docket to receive suggestions, recommendations, and
comments on innovative packaging, storage, and disposal systems,
technologies or designs (``designs'') that could be used to prevent or
deter misuse and abuse of opioid analgesics by patients and others. FDA
is interested in receiving comments on new designs as well as
enhancements to existing designs, and is particularly interested in
comments from academic institutions, regulated industry, technology
companies (e.g., those producing technologies for medication adherence,
disposal, or tracking), healthcare professionals, patient
representatives, clinical trial service providers, and other interested
organizations. Comments submitted in response to this notice will help
the Agency determine whether innovative designs for opioid analgesic
packaging, storage, and/or disposal systems could help prevent or deter
misuse and abuse without diminishing access for patients with
legitimate prescriptions.

DATES: Submit either electronic or written comments by June 9, 2014.

ADDRESSES: Submit electronic comments to http://www.regulations.gov.
Submit written comments to the Division of Dockets Management (HFA-
301), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852. Identify comments with the docket number found in
brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Colleen Brennan, Center for Drug
Evaluation and Research, Office of Surveillance and Epidemiology, Food
and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4410,
Silver Spring, MD 20993-0002,<PHONE_NUMBER>, email:
<EMAIL_ADDRESS>with the subject line identified as
``Packaging Abuse Deterrence Strategies.''

SUPPLEMENTARY INFORMATION:

I. Background

    Prescription opioid analgesics are important medications that are
widely prescribed for the treatment of both non-cancer and cancer-
related pain. When used properly for their approved indications, opioid
drugs provide significant benefits for patients. However, they also
carry a risk of misuse, abuse, addiction, overdose, and death.
According to an analysis from the Centers for Disease Control and
Prevention, in 2010, prescription opioid drugs were involved in 16,651
overdose deaths, which represented a 313 percent increase over the past
decade (Ref. 1). The Substance Abuse and Mental Health Services
Administration (SAMHSA) reports that for each overdose death, there
were an additional 11 treatment admissions (Ref. 2), 33 emergency
department visits (Ref. 3), and 880 non-medical users of these drugs
(Ref. 4).
    Although inappropriate or illicit use, such as sharing the drug
with family and friends or using drugs stolen from home medicine
cabinets account for some of the problems with prescription opioids,
legitimate use of opioids for pain may also lead to adverse events,
addiction, and death. FDA plays a central role in the development,
review, and approval of opioid drug products and must strike a balance
between their benefit in the legitimate treatment of patients with pain
and the risks to those patients and others associated with misuse,
abuse, and addiction.
    Combating opioid misuse, abuse, and addiction has long been both a
public health priority and a priority for the Agency. FDA has taken
many steps to address these problems; however, we recognize that more
can be done and have established a task force that has embarked on a
multi-pronged approach, building upon existing initiatives and
developing new initiatives (http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm337852.htm). Exploring innovative designs for
drug packaging, storage, and/or disposal is one of the many initiatives
targeted by the task force.
    Designs for drug packaging, storage, and disposal have evolved
considerably in the past decade to include many technology-based
features such as electronic systems for monitoring, assessing, and
improving adherence to medication regimens. For example, these systems
may include functionality to remind patients to take a dose, track

when a dose is taken and how much is taken, and limit further access
until it is time for the next dose. Additionally, many of these drug-
device combinations electronically encrypt and capture the accumulated
adherence data, which can be downloaded directly from the device or
wirelessly transmitted to the prescriber. These technologies have not
only been used in clinical management and monitoring of protocol
compliance in clinical trials, but have also been applied to combat the
problem of prescription opioid misuse and abuse.
    Other potentially relevant technologies include ``track and trace''
capabilities, radio-frequency identification-based systems, microchips
embedded within tablets, and in-home medication deactivation and/or
disposal systems.
    FDA is interested in further exploring the role of existing and
innovative designs for drug product packaging, storage, and/or disposal
in mitigating opioid misuse, abuse, and addiction. For example, many of
the features of medication adherence monitoring technologies could be
used or adapted to help prevent serious complications (e.g., overdose,
addiction) by supporting proper dosage and administration, and could
also help prescribers monitor for signs of abuse or medication sharing
by facilitating effective patient management and followup.
Additionally, medication packaging and/or storage designs that limit
access could help prevent use of the medication by someone for whom it
was not prescribed, thereby, preventing accidental exposure (e.g., by a
child or other household contact) or theft. Finally, medication
packaging, storage, and/or disposal designs could be applied or adapted
to help ensure safe disposal, including chemical deactivation, of any
unused or residual medication.

II. Establishment of a Docket

    FDA is announcing the establishment of a public docket to provide
an opportunity for interested persons to share information, research,
and ideas on how drug product packaging, storage, and/or disposal
systems could be designed or adapted to address problems associated
with prescription opioid abuse and misuse. These comments will help the
Agency explore whether existing or innovative designs can be applied or
adapted to prevent or deter misuse and abuse, while ensuring that
patients in pain have appropriate access to opioid analgesics.

III. Suggestions for Those Submitting Comments in Response to This
Notice

    Proposed packaging, storage, and/or disposal designs should be
feasible to implement, and should not impair access for patients who
have legitimate prescriptions. Comments about specific system or
technology designs should include a description of the following: (1)
Design features and functionality; (2) results of any formative or
summative human factors assessments conducted; (3) applications to
date, including information on the effectiveness and acceptability of
those applications (with literature references or other documentation);
(4) recommendations for how the system/technology design could be
applied or adapted (either alone and/or in combination with other
systems/technologies) to help prevent or deter misuse and abuse, and
any limitations of that application; (5) specific problems that could
be addressed (e.g., serious complications such as addiction or overdose
due to improper dosage and/or administration, improper disposal,
accidental use by someone for whom the medication was not prescribed);
and (6) to the extent possible, considerations for implementation into
routine dispensing and clinical use (e.g., how the solution would
impact the workflow in a retail pharmacy).
    To help FDA prioritize among proposed approaches, the Agency is
also interested in receiving feedback about methods that could be used
to assess a system or technology's potential abuse-deterrent
characteristics and real-world impact (e.g., actual ability to prevent
or deter misuse and abuse, effect on access for appropriate patients,
patient confidentiality, burden on the healthcare system, feasibility
of implementation, whether the design could create unintended
medication errors). Finally, FDA is interested in receiving feedback on
methods for encouraging further research and development in this area,
and, if promising technologies are identified, incentivizing the
pharmaceutical industry (e.g. via patent extensions) to adopt such
technologies.

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. 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. The Agency will carefully consider all comments
submitted. FDA generally will not respond directly to the person or
organization submitting the comment.

V. References

    The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
(FDA has verified the Web site addresses, but FDA is not responsible
for any subsequent changes to the Web sites after this document
publishes in the Federal Register.)

    1. Centers for Disease Control and Prevention. ``Opioids drive
continued increase in drug overdose deaths'' [Press Release] (2013).
http://www.cdc.gov/media/releases/2013/p0220_drug_overdose_deaths.html.
    2. SAMHSA, Center for Behavioral Health Statistics and Quality.
Treatment Episode Data Set (TEDS): 2001-2011. National Admissions to
Substance Abuse Treatment Services. BHSIS Series S-65, HHS
Publication No. (SMA) 13-4772. Rockville, MD: Substance Abuse and
Mental Health Services Administration, 2013.
    3. SAMHSA, Center for Behavioral Health Statistics and Quality,
``Drug Abuse Warning Network,'' 2011. http://samhsa.gov/data/dawn/nations/Nation_2011_AllMA.xls.
    4. Substance Abuse and Mental Health Services Administration,
Results from the 2012 National Survey on Drug Use and Health,
detailed table 1.1A, NSDUH Series H-46, HHS Publication No. (SMA)
13-4795. Rockville, MD: Substance Abuse and Mental Health Services
Administration, 2013.

    Dated: April 2, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-07909 Filed 4-8-14; 8:45 am]
BILLING CODE 4160-01-P