[Federal Register Volume 73, Number 59 (Wednesday, March 26, 2008)]
[Notices]
[Pages 16025-16026]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 08-1077]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0145]


Preparation for International Conference on Harmonization 
Meetings in Portland, Oregon; Public Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a public 
meeting entitled ``Preparation for ICH Meetings in Portland, Oregon'' 
to provide information and receive comments on the International 
Conference on Harmonization (ICH) as well as the upcoming meetings in 
Portland, Oregon. The topics to be discussed are the topics for 
discussion at the forthcoming ICH Steering Committee Meeting. The 
purpose of the meeting is to solicit public input prior to the next 
Steering Committee and Expert Working Groups meetings in Portland, 
Oregon, June 2-5, 2008, at which discussion of the topics underway and 
the future of ICH will continue.
    Date and Time: The meeting will be held on Friday April 4, 2008, 
from 12:30 pm to 5 p.m.
    Location: The meeting will be held at 5600 Fishers Lane, 3rd floor, 
Conference Room G and H, Rockville, MD 20857. For security reasons, all 
attendees are asked to arrive no later than 12:25 p.m., as you will be 
escorted from the front entrance of 5600 Fishers Lane to Conference 
Room G and H.
    Contact Person: All participants must register with Tammie Bell, 
Office of the Commissioner, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, by e-mail: [email protected] or FAX: 
301-480-0003.
    Registration and Requests for Oral Presentations: Send registration 
information (including name, title, firm name, address, telephone, and 
fax number), written material, and requests to make oral presentations, 
to the contact person by April 3, 2008.
    If you need special accommodations due to a disability, please 
contact Tammie Bell at least 7 days in advance.

SUPPLEMENTARY INFORMATION: The ICH was established in 1990 as a joint 
regulatory/industry project to improve, through harmonization, the 
efficiency of the process for developing and registering new medicinal 
products in Europe, Japan, and the United States without compromising 
the regulatory obligations of safety and effectiveness.
    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for medical product development among regulatory agencies. 
ICH was organized to provide an opportunity for harmonization 
initiatives to be developed with input from both regulatory and 
industry representatives. ICH is concerned with harmonization among 
three regions: The European Union, Japan, and the United States. The 
six ICH sponsors are the European Commission; the European Federation 
of Pharmaceutical Industries Associations; the Japanese Ministry of 
Health, Labor and Welfare; the Japanese Pharmaceutical Manufacturers 
Association; the Centers for Drug Evaluation and Research and Biologics 
Evaluation and Research, FDA; and the Pharmaceutical Research and 
Manufacturers of America. The ICH Secretariat, which coordinates the 
preparation of documentation, is provided by the International 
Federation of Pharmaceutical Manufacturers Associations (IFPMA). The 
ICH Steering Committee includes representatives from each of the ICH

[[Page 16026]]

sponsors and Health Canada, the European Free Trade Area, and the World 
Health Organization. The ICH process has achieved significant 
harmonization of the technical requirements for the approval of 
pharmaceuticals for human use in the three ICH regions.
    The current ICH process and structure can be found at the following 
Web site: http://www.ich.org.
    The agenda for the public meeting will be made available via the 
internet at http://www.fda.gov/cder/meeting/ICH_20080404.htm.
    One of the agenda items that will be discussed at the meeting will 
be the revised ICH S2 (R1) guidance. Elsewhere in this issue of the 
Federal Register, FDA is publishing a related document entitled 
``International Conference on Harmonisation; Draft Guidance on S2(R1) 
Genotoxicity Testing and Data Interpretation for Pharmaceuticals 
Intended for Human Use; Availability.''
    The revised ICH S2 Guidance proposes a new set of options for 
genetic toxicity testing. A primary impetus for these new testing 
options has been the occurrence of a high frequency of in vitro 
mammalian cell assay positive results and questions of the relevance of 
these positive results. The proposed new test battery consists of a 
bacterial mutation (Ames) assay followed by a choice of two options. 
The first option is similar to the present battery although the limit 
dose for the in vitro mammalian cell assays has been lowered 10-fold to 
1 millimolar and the in vitro micronucleus test is introduced as an 
alternative for the in vitro mammalian test. The second option consists 
of two in vivo endpoints. The in vitro mammalian tests are not required 
for option 2. The first in vivo test is the micronucleus endpoint; 
however, the identity of the second in vivo test has been left open.
    The rationale and scientific data to support the proposed changes 
in the revised ICH S2 Guidance will be discussed.

Specific Questions for the Public Meeting on Revised ICH S2 Guidance

    1. The perceived problem with the current battery, as articulated 
in the new guidance, is that there are too many irrelevant (false) in 
vitro mammalian cell assay positive results. Are there sufficient 
scientific data (preferably published) that support the proposed 
changes in the revised guidance? Does the new battery address this 
issue without missing genotoxicants?
    2. Most regulatory agencies use the same battery of genetic 
toxicology tests as described in the ICH S2A and SB Guidances. What is 
the rationale for having a different genetic toxicity battery to 
support safety determinations for pharmaceuticals, versus for other 
chemical substances?
    3. Is it reasonable, as part of ICH Guidance, to give sponsors an 
option of two test batteries? Are option 1 and option 2 test batteries 
equivalent? When would you use one and when would you use the other?
    4. FDA has put in place new recommendations (``Guidance for 
Industry and Review Staff Recommended Approaches to Integration of 
Genetic Toxicology Study Results,'' published in January 2006) 
concerning the interpretation of genotoxicity data (weight-of-evidence 
approach). Have standards and recommendations for interpretation of 
current genetox batteries sufficiently addressed interpretation of 
results to obviate the need for changing the battery itself? Supporting 
data would be helpful.
    5. Is the lowering of the maximum concentration in the in vitro 
mammalian assays by an order of magnitude scientifically justified?
    6. Do the changes in the ICH Guidance adequately address accuracy 
(which requires both sensitivity and specificity)?
    Interested persons may present data, information, or views orally 
or in writing, on issues pending at the public meeting. The public oral 
presentations schedule can be found on the ICH public meeting agenda. 
Time allotted for oral presentations may be limited to 10 minutes. 
Those desiring to make oral presentations should notify the contact 
person by April 3, 2008, and submit a brief statement of the general 
nature of the evidence or arguments they wish to present, the names and 
addresses, phone number, fax, and e-mail of proposed participants, and 
an indication of the approximate time requested to make their 
presentation.
    Transcripts: Please be advised that as soon as a transcript is 
available, it can be obtained in either hardcopy or on CD-ROM, after 
submission of a Freedom of Information request. Written requests are to 
be sent to Division of Freedom of Information (HFI-35), Office of 
Management Programs, Food and Drug Administration, 5600 Fishers Lane, 
rm. 6-30, Rockville, MD 20857.

    Dated: March 20, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. 08-1077 Filed 3-21-08; 3:05 pm]
BILLING CODE 4160-01-S