
[Federal Register: March 26, 2010 (Volume 75, Number 58)]
[Notices]               
[Page 14602-14603]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26mr10-59]                         

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-D-0143] (formerly Docket No. FDA-2008-D-0128)

 
Guidance for Industry on Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation; Opening of Comment Period for Future Revision of 
Guidance Dated July 2009; Public Conference

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice of opening of comment period; notice of public 
conference.

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

SUMMARY:  The Food and Drug Administration (FDA) is opening a comment 
period for submission of suggestions for revising the guidance for 
industry published in the Federal

[[Page 14603]]

Register July 30, 2009, entitled ``Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation.'' In addition, FDA, along with the 
American Association for the Study of Liver Diseases (AASLD) and the 
Pharmaceutical and Research Manufacturers of America, is sponsoring a 
public conference to be held on March 24 and 25, 2010, to discuss and 
debate issues contained in the published guidance document. The purpose 
of the conference is to consider the effect of the recommendations in 
the guidance since its publication, and to seek suggestions for future 
revisions that will incorporate the views expressed.

DATES:  The public conference will be held on March 24, 2010, from 8 
a.m. to 6 p.m. and March 25, 2010, from 8 a.m. until 3:15 p.m. Submit 
written or electronic comments on agency guidances at any time.

ADDRESSES:  The conference will take place at the National Labor 
College, 10000 New Hampshire Ave., Silver Spring MD 20993.
    Submit written requests for single copies of the July 2009 guidance 
to the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, rm. 2201, Silver Spring, MD 20993-0002. Send one self-addressed 
adhesive label to assist that office in processing your requests. 
Submit written comments on the guidance to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852. Submit electronic comments to http://
www.regulations.gov. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Lana L. Pauls, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, rm. 4307, Silver Spring MD 20993-0002, 301-
796-0518, e-mail: lana.pauls@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA announced in July 2009 the availability of a guidance for 
industry entitled ``Guidance for Industry on Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation.'' The guidance explained that drug-
induced liver injury (DILI) has been the most frequent cause of acute 
liver failure in the United States in the last 10 years, exceeding all 
other causes combined. It discussed methods of detecting DILI by 
periodic tests of serum enzyme activities and bilirubin concentration 
elevations, and how those laboratory tests might change over time, 
along with symptoms and physical findings, to allow estimation of 
severity of the injury. It suggested some rules for stopping or 
interrupting drug treatment, and the need to obtain additional clinical 
information to estimate the likelihood of the true cause. Previous 
periods for comments on the draft guidance were opened in 2007 and 
2008, and those comments were taken into consideration when issuing the 
final guidance in July 2009. The guidance was issued consistent with 
FDA's good guidance practices regulation (21 CFR 10.115), representing 
the agency's current thinking on evidence for DILI in premarketing 
clinical evaluation. It does not create or confer any rights for or on 
any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the 
requirements of the applicable statutes and regulations.

II. The Public Conference

A. Why Are We Holding This Conference?

    The purpose of the 2010 conference is to discuss the most current 
information and thinking about clinical and basic aspects of the still-
unsolved problems of exactly how drugs cause liver injury and why 
certain individual people are more susceptible than others, combining 
views of both basic science and clinical experts, and selecting for 
specific debate and discussion some controversial issues such as:
     Whether indications of cholestasis (biliary tract 
obstruction) are less important than evidence of primarily 
hepatocellular injury with secondary functional impairment;
     What findings could lead to interrupting or permanently 
stopping administration of new drugs under evaluation; and
     The appropriate use of rechallenge testing to study 
hepatotoxicity.

B. Is There a Fee and How Do I Register for the Conference?

    A modest registration fee will be charged to attendees other than 
invited speakers, to help defray the costs of rental of the meeting 
spaces, meals and snacks provided, and if possible to cover travel 
costs incurred by invited academic (but not Government or industry) 
speakers, and other costs. The fee for the 2-day meeting for industry 
registrants is $450, and $225 for Federal Government and academic 
registrants. Registration fees will be waived for invited speakers and 
moderators.
    The registration process will be handled by AASLD, a not-for-profit 
organization which has extensive experience in planning, organizing, 
and executing educational meetings.
    The presentations and discussions will be recorded and published on 
the Internet for public availability after minor editing by FDA. It 
will then be posted on the Internet by AASLD following the meeting, to 
allow consideration of the issues and material presented by those 
unable to attend the conference in person.
    Additional information on the conference, program, and registration 
procedures, as well as on past conferences 2001 through 2009, is 
available on the Internet at http://www.aasld.org (go to Conferences 
and Education, Meetings and Conferences), and also at http://
www.fda.gov by typing into the search box ``liver toxicity.'' (FDA has 
verified the AASLD Web site address, but FDA is not responsible for any 
subsequent changes to the Web site after this document publishes in the 
Federal Register.)

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding the guidance 
and the issues and questions presented at the conference. Submit a 
single copy of electronic comments or two paper copies of any mailed 
comments, except that individuals may submit one paper copy. Comments 
are to be identified 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.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/
GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http:/
/www.regulations.gov.

    Dated: March 17, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-6701 Filed 3-25-10; 8:45 am]
BILLING CODE 4160-01-S

