81_FR_2232 81 FR 2222 - How Should Liver Injury and Dysfunction Caused by Drugs Be Measured, Evaluated, and Acted Upon in Clinical Trials?

81 FR 2222 - How Should Liver Injury and Dysfunction Caused by Drugs Be Measured, Evaluated, and Acted Upon in Clinical Trials?

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 10 (January 15, 2016)

Page Range2222-2223
FR Document2016-00690

The Food and Drug Administration (FDA) is announcing a public conference entitled ``How Should Liver Injury and Dysfunction Caused by Drugs Be Measured, Evaluated, and Acted Upon in Clinical Trials?'' This conference will be cosponsored with the Critical Path Institute (C- Path). The purpose of the conference is to discuss, debate, and share views among stakeholders in academia, patient groups, regulatory bodies, and the health care and pharmaceutical industries on how best to measure, evaluate, and act upon liver injury and dysfunction caused by drugs used during clinical trials.

Federal Register, Volume 81 Issue 10 (Friday, January 15, 2016)
[Federal Register Volume 81, Number 10 (Friday, January 15, 2016)]
[Notices]
[Pages 2222-2223]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-00690]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0128 (formerly Docket No. 2007D-0396)]


How Should Liver Injury and Dysfunction Caused by Drugs Be 
Measured, Evaluated, and Acted Upon in Clinical Trials?

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public conference.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing a public 
conference entitled ``How Should Liver Injury and Dysfunction Caused by 
Drugs Be Measured, Evaluated, and Acted Upon in Clinical Trials?'' This 
conference will be cosponsored with the Critical Path Institute (C-
Path). The purpose of the conference is to discuss, debate, and share 
views among stakeholders in academia, patient groups, regulatory 
bodies, and the health care and pharmaceutical industries on how best 
to measure, evaluate, and act upon liver injury and dysfunction caused 
by drugs used during clinical trials.

DATES: This public conference will be held on March 23, 2016, from 8 
a.m. to 6 p.m., and on March 24, 2016, from 8 a.m. to 4 p.m.

ADDRESSES: This public conference will be held at the College Park 
Marriott Hotel & Conference Center, 3501 University Blvd., East 
Hyattsville, MD 20783. The hotel's phone number is 301-985-7300.

FOR FURTHER INFORMATION CONTACT: Lana L. Pauls, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 4478, Silver Spring, MD 20993-0002, 301-
796-0518, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    In July 2009, FDA announced the availability of a guidance for 
industry entitled ``Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation'' (74 FR 38035, July 30, 2009, https://www.thefederalregister.org/fdsys/pkg/FR-2009-07-30/pdf/E9-18135.pdf). First, this guidance explains that 
drug-induced liver injury (DILI) has been the most frequent cause

[[Page 2223]]

of safety-related drug marketing withdrawals over the past 50 years and 
that hepatotoxicity has both limited the use of many drugs that have 
been approved and prevented the approval of others. Second, this 
guidance discusses methods of detecting DILI by periodic tests of serum 
enzyme activities and of bilirubin concentration and how changes in the 
results of these laboratory tests over time, along with symptoms and 
physical findings, may be used to estimate the severity of the injury. 
Third, this guidance suggests some ``stopping rules'' for interrupting 
drug treatment and mentions the need to obtain sufficient clinical 
information to assess causation. FDA published a draft of this guidance 
in 2006, and comments on that draft were taken into consideration when 
issuing the final guidance in July 2009.

II. Conference Information

    The purpose of the 2016 conference is to invite participants to 
present their data and views and to hold an open discussion. The 
meetings in recent years have been attended by members of industry, 
regulatory bodies, and academic consultants, and the topics discussed 
have included several unresolved issues on which consensus was sought.
    Registration: A registration fee ($650 for industry registrants and 
$325 for Federal government and academic registrants) will be charged 
to help defray the cost of renting the meeting space, providing meals 
and snacks, and covering the travel fees incurred by invited academic 
(but not government or industry) speakers, as well as any other 
expenses. The registration process will be handled by C-Path, an 
independent, nonprofit organization established in 2005 with public and 
private philanthropic support from the southern Arizona community, 
Science Foundation Arizona, and FDA.
    Additional information on the conference, program, and registration 
procedures may be obtained on the Internet at http://www.c-path.org, 
and at http://www.fda.gov by typing ``liver toxicity'' into the search 
box. (FDA has verified the Web site addresses but is not responsible 
for any subsequent changes to the Web sites after this document 
publishes in the Federal Register.)
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at http://www.regulations.gov. It may 
be viewed at the Division of Dockets Management, Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD. A 
transcript will also be available in either hardcopy or on CD-ROM, 
after submission of a Freedom of Information request. The Freedom of 
Information office address is available on the Agency's Web site at 
http://www.fda.gov.
    Materials presented at past programs (from 2007 to 2015) (including 
copies of slides shown, comments made about the slides, and discussions 
following the slides) may be accessed at http://www.aasld.org/events-professional-development/drug-induced-liver-injury-2015-program. (FDA 
has verified this Web site address but is not responsible for any 
subsequent changes to it after this document publishes in the Federal 
Register.)

    Dated: January 8, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-00690 Filed 1-14-16; 8:45 am]
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                                                  2222                                      Federal Register / Vol. 81, No. 10 / Friday, January 15, 2016 / Notices

                                                  ‘‘reasonably needed to treat, diagnose,                                    petition to modify the ADN if additional                                     availability of the draft guidance
                                                  or cure a population of 4,000                                              information arises.                                                          entitled ‘‘Humanitarian Device
                                                  individuals in the United States’’, and                                       On August 5, 2008, FDA issued a                                           Exemption: Questions and Answers;
                                                  therefore shall be based on the following                                  guidance entitled ‘‘Guidance for HDE                                         Draft Guidance for Humanitarian Device
                                                  information in a HDE application: The                                      Holders, Institutional Review Boards                                         Exemption Holders, Institutional
                                                  number of devices reasonably necessary                                     (IRBs), Clinical Investigators, and Food                                     Review Boards, Clinical Investigators,
                                                  to treat such individuals.                                                 and Drug Administration Staff—                                               and Food and Drug Administration
                                                                                                                             Humanitarian Device Exemption (HDE)                                          Staff’’, that when finalized, will
                                                     Section 520(m)(6)(A)(iii) of the FD&C                                   Regulation: Questions and Answers’’
                                                  Act (http://www.fda.gov/Regulatory                                                                                                                      represent FDA’s current thinking on this
                                                                                                                             (http://www.fda.gov/downloads/                                               topic.
                                                  Information/Legislation/Federal                                            MedicalDevices/DeviceRegulationand
                                                  FoodDrugandCosmeticActFDCAct/                                              Guidance/GuidanceDocuments/                                                    FDA is requesting the extension of
                                                  FDCActChapterVDrugsandDevices/                                             ucm110203.pdf). The guidance was                                             OMB approval for the collection of
                                                  default.htm) provides that an HDE                                          developed and issued prior to the                                            information required under the statutory
                                                  holder immediately notify the Agency if                                    enactment of FDASIA, and certain                                             mandate of sections 515A (21 U.S.C.
                                                  the number of devices distributed                                          sections of this guidance may no longer                                      360e–1) and 520(m) of the FD&C Act as
                                                  during any calendar year exceeds the                                       be current as a result of FDASIA. In the                                     amended.
                                                  ADN. Section 520(m)(6)(C) of the FD&C                                      Federal Register of March 18, 2014 (79                                         FDA estimates the burden of this
                                                  Act provides that an HDE holder may                                        FR 15130), FDA announced the                                                 collection of information as follows:

                                                                                                                 TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN
                                                                                                                                                                             Number of                                                Average
                                                                                                                                                  Number of                                            Total annual
                                                     Activity/section of FD&C Act (as amended) or FDASIA                                                                   responses per                                            burden per              Total hours
                                                                                                                                                 respondents                                            responses
                                                                                                                                                                             respondent                                              response

                                                  Pediatric Subpopulation and Patient Information—
                                                    515A(a)(2) of the FD&C Act .............................................                                          6                          1                         6                       100               600
                                                  Exemption     from         Profit         Prohibition           Information—
                                                    520(m)(6)(A)(i) and (ii) of the FD&C Act ..........................                                               3                         1                           3                        50              150
                                                  Request for Determination of Eligibility Criteria—613(b) of
                                                    FDASIA .............................................................................                             2                           1                         2                       10                 20
                                                  ADN Notification—520(m)(6)(A)(iii) of the FD&C Act ..........                                                      1                           1                         1                      100                100
                                                  ADN Modification—520(m)(6)(C) of the FD&C Act .............                                                        5                           1                         5                      100                500

                                                        Total ..............................................................................    ........................   ........................   ........................   ........................          1,370
                                                     1 There    are no capital costs or operating and maintenance costs associated with this collection of information.


                                                    FDA’s Center for Devices and                                             DEPARTMENT OF HEALTH AND                                                     dysfunction caused by drugs used
                                                  Radiological Health receives an                                            HUMAN SERVICES                                                               during clinical trials.
                                                  estimated average of six HDE                                                                                                                            DATES: This public conference will be
                                                  applications per year. FDA estimates                                       Food and Drug Administration                                                 held on March 23, 2016, from 8 a.m. to
                                                  that three of these applications will be                                                                                                                6 p.m., and on March 24, 2016, from 8
                                                  indicated for pediatric use. We estimate                                   [Docket No. FDA–2008–D–0128 (formerly                                        a.m. to 4 p.m.
                                                                                                                             Docket No. 2007D–0396)]
                                                  that we will receive approximately two                                                                                                                  ADDRESSES: This public conference will
                                                  requests for determination of eligibility                                  How Should Liver Injury and                                                  be held at the College Park Marriott
                                                  criteria per year. FDA estimates that                                      Dysfunction Caused by Drugs Be                                               Hotel & Conference Center, 3501
                                                  very few or no HDE holders will notify                                     Measured, Evaluated, and Acted Upon                                          University Blvd., East Hyattsville, MD
                                                  the Agency that the number of devices                                      in Clinical Trials?                                                          20783. The hotel’s phone number is
                                                  distributed in the year has exceeded the                                                                                                                301–985–7300.
                                                  ADN. FDA estimates that five HDE                                           AGENCY:           Food and Drug Administration,                              FOR FURTHER INFORMATION CONTACT:
                                                  holders will petition to have the ADN                                      HHS.                                                                         Lana L. Pauls, Center for Drug
                                                  modified due to additional information                                     ACTION:       Notice of public conference.                                   Evaluation and Research, Food and
                                                  on the number of individuals affected                                                                                                                   Drug Administration, 10903 New
                                                                                                                             SUMMARY:   The Food and Drug                                                 Hampshire Ave., Bldg. 22, Rm. 4478,
                                                  by the disease or condition.
                                                                                                                             Administration (FDA) is announcing a                                         Silver Spring, MD 20993–0002, 301–
                                                    Dated: January 11, 2016.                                                 public conference entitled ‘‘How Should                                      796–0518, lana.pauls@fda.hhs.gov.
                                                  Leslie Kux,                                                                Liver Injury and Dysfunction Caused by                                       SUPPLEMENTARY INFORMATION:
                                                  Associate Commissioner for Policy.                                         Drugs Be Measured, Evaluated, and
                                                                                                                             Acted Upon in Clinical Trials?’’ This                                        I. Background
                                                  [FR Doc. 2016–00691 Filed 1–14–16; 8:45 am]
                                                                                                                             conference will be cosponsored with the                                         In July 2009, FDA announced the
                                                  BILLING CODE 4164–01–P
mstockstill on DSK4VPTVN1PROD with NOTICES




                                                                                                                             Critical Path Institute (C-Path). The                                        availability of a guidance for industry
                                                                                                                             purpose of the conference is to discuss,                                     entitled ‘‘Drug-Induced Liver Injury:
                                                                                                                             debate, and share views among                                                Premarketing Clinical Evaluation’’ (74
                                                                                                                             stakeholders in academia, patient                                            FR 38035, July 30, 2009, https://
                                                                                                                             groups, regulatory bodies, and the                                           www.gpo.gov/fdsys/pkg/FR-2009-07-30/
                                                                                                                             health care and pharmaceutical                                               pdf/E9-18135.pdf). First, this guidance
                                                                                                                             industries on how best to measure,                                           explains that drug-induced liver injury
                                                                                                                             evaluate, and act upon liver injury and                                      (DILI) has been the most frequent cause


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                                                                                 Federal Register / Vol. 81, No. 10 / Friday, January 15, 2016 / Notices                                                  2223

                                                  of safety-related drug marketing                        either hardcopy or on CD–ROM, after                    neighborhood organizations in order to:
                                                  withdrawals over the past 50 years and                  submission of a Freedom of Information                 Identify best practices and successful
                                                  that hepatotoxicity has both limited the                request. The Freedom of Information                    modes of delivering social services;
                                                  use of many drugs that have been                        office address is available on the                     evaluate the need for improvements in
                                                  approved and prevented the approval of                  Agency’s Web site at http://                           the implementation and coordination of
                                                  others. Second, this guidance discusses                 www.fda.gov.                                           public policies relating to faith- based
                                                  methods of detecting DILI by periodic                      Materials presented at past programs                and other neighborhood organizations;
                                                  tests of serum enzyme activities and of                 (from 2007 to 2015) (including copies of               and make recommendations for changes
                                                  bilirubin concentration and how                         slides shown, comments made about the                  in policies, programs, and practices.
                                                  changes in the results of these                         slides, and discussions following the                    Contact Person for Additional
                                                  laboratory tests over time, along with                  slides) may be accessed at http://                     Information: Please contact Ben O’Dell
                                                  symptoms and physical findings, may                     www.aasld.org/events-professional-                     for any additional information about the
                                                  be used to estimate the severity of the                 development/drug-induced-liver-injury-                 President’s Advisory Council meeting at
                                                  injury. Third, this guidance suggests                   2015-program. (FDA has verified this                   partnerships@hhs.gov.
                                                  some ‘‘stopping rules’’ for interrupting                Web site address but is not responsible                  Agenda: For February 1, the agenda
                                                  drug treatment and mentions the need                    for any subsequent changes to it after                 will begin with an Opening and
                                                  to obtain sufficient clinical information               this document publishes in the Federal                 Welcome from the Chairperson and
                                                  to assess causation. FDA published a                    Register.)                                             Executive Director for the President’s
                                                  draft of this guidance in 2006, and                       Dated: January 8, 2016.                              Advisory Council for Faith-based and
                                                  comments on that draft were taken into
                                                                                                          Leslie Kux,                                            Neighborhood Partnership. Then there
                                                  consideration when issuing the final
                                                                                                          Associate Commissioner for Policy.                     will be presentation of any
                                                  guidance in July 2009.
                                                                                                          [FR Doc. 2016–00690 Filed 1–14–16; 8:45 am]            Recommendations for deliberation and
                                                  II. Conference Information                              BILLING CODE 4164–01–P                                 vote. Lastly, there will be a discussion
                                                     The purpose of the 2016 conference is                                                                       of subgroup deliberation as well as
                                                  to invite participants to present their                                                                        elements being considered for
                                                  data and views and to hold an open                      DEPARTMENT OF HEALTH AND                               recommendations. For February 2, there
                                                  discussion. The meetings in recent years                HUMAN SERVICES                                         will presentations on work to address
                                                  have been attended by members of                                                                               poverty and income inequality after a
                                                  industry, regulatory bodies, and                        Meeting Notice for the President’s                     welcome and opening from the
                                                  academic consultants, and the topics                    Advisory Council on Faith-Based and                    Chairperson and Executive Director for
                                                  discussed have included several                         Neighborhood Partnerships                              the President’s Advisory Council.
                                                  unresolved issues on which consensus                       In accordance with section 10(a)(2) of                Public Comment: There will be an
                                                  was sought.                                             the Federal Advisory Committee Act                     opportunity for public comment at the
                                                     Registration: A registration fee ($650               (Pub. L. 92–463), the President’s                      end of the meeting. Comments and
                                                  for industry registrants and $325 for                   Advisory Council on Faith-based and                    questions can be sent in advance to
                                                  Federal government and academic                         Neighborhood Partnerships announces                    partnerships@hhs.gov.
                                                  registrants) will be charged to help                    the following meetings:                                  Dated: January 11, 2016.
                                                  defray the cost of renting the meeting                     Name: President’s Advisory Council                  Ben O’Dell,
                                                  space, providing meals and snacks, and                  on Faith-based and Neighborhood                        Associate Director for Center for Faith-based
                                                  covering the travel fees incurred by                    Partnerships Council Meetings.                         and Neighborhood Partnerships at U.S.
                                                  invited academic (but not government                       Time and Date: Monday, February                     Department of Health and Human Services.
                                                  or industry) speakers, as well as any                   1st, 2016 1:00 p.m.–5:00 p.m. (EST) and                [FR Doc. 2016–00767 Filed 1–14–16; 8:45 am]
                                                  other expenses. The registration process                Tuesday, February 2nd, 2016 10:00                      BILLING CODE 4154–07–P
                                                  will be handled by C-Path, an                           a.m.–1:00 p.m. (EST).
                                                  independent, nonprofit organization                        Place: Meeting will be held at a
                                                  established in 2005 with public and                     location to be determined in the White                 DEPARTMENT OF HEALTH AND
                                                  private philanthropic support from the                  House complex, 1600 Pennsylvania Ave                   HUMAN SERVICES
                                                  southern Arizona community, Science                     NW., Washington, DC. Space is
                                                  Foundation Arizona, and FDA.                            extremely limited. Photo ID and RSVP                   National Institutes of Health
                                                     Additional information on the                        by January 25, 2016 are required to
                                                  conference, program, and registration                   attend the event. Please RSVP to Ben                   Center for Scientific Review; Notice of
                                                  procedures may be obtained on the                       O’Dell at partnerships@hhs.gov.                        Closed Meetings
                                                  Internet at http://www.c-path.org, and at                  The meeting will be available to the
                                                  http://www.fda.gov by typing ‘‘liver                    public through a conference call line.                   Pursuant to section 10(d) of the
                                                  toxicity’’ into the search box. (FDA has                Register to participate in the conference              Federal Advisory Committee Act, as
                                                  verified the Web site addresses but is                  call on Monday, February 1st at the Web                amended (5 U.S.C. App.), notice is
                                                  not responsible for any subsequent                      site https://attendee.gotowebinar.com/                 hereby given of the following meetings.
                                                  changes to the Web sites after this                     register/7321886895235169026. Register                   The meetings will be closed to the
                                                  document publishes in the Federal                       to participate in the conference call on               public in accordance with the
                                                  Register.)                                              Tuesday, February 2nd at the Web site                  provisions set forth in sections
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                                                     Transcripts: Please be advised that as               https://attendee.gotowebinar.com/                      552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
                                                  soon as a transcript is available, it will              register/4788059050490531842.                          as amended. The grant applications and
                                                  be accessible at http://                                   Status: Open to the public, limited                 the discussions could disclose
                                                  www.regulations.gov. It may be viewed                   only by space available. Conference call               confidential trade secrets or commercial
                                                  at the Division of Dockets Management,                  limited only by lines available.                       property such as patentable material,
                                                  Food and Drug Administration, 5630                         Purpose: The Council brings together                and personal information concerning
                                                  Fishers Lane, Rm. 1061, Rockville, MD.                  leaders and experts in fields related to               individuals associated with the grant
                                                  A transcript will also be available in                  the work of faith-based and                            applications, the disclosure of which


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Document Created: 2018-02-02 12:31:47
Document Modified: 2018-02-02 12:31:47
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice of public conference.
DatesThis public conference will be held on March 23, 2016, from 8 a.m. to 6 p.m., and on March 24, 2016, from 8 a.m. to 4 p.m.
ContactLana L. Pauls, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4478, Silver Spring, MD 20993-0002, 301- 796-0518, [email protected]
FR Citation81 FR 2222 

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