2010-6701. 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 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: [e-mail].

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.