Federal Register / Vol. 73, No. 59 / Wednesday, March 26, 2008 / Notices 16025 

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 

sponsors and the IFPMA, as well as 

observers from the World Health 

Organization, Health Canada, and the 

European Free Trade Area. 

In February 2008, the ICH Steering 

Committee agreed that a draft guidance 

entitled ‘‘S2(R1) Genotoxicity Testing 

and Data Interpretation for 

Pharmaceuticals Intended for Human 

Use’’ should be made available for 

public comment. The draft guidance is 

the product of the Safety Expert 

Working Group of the ICH. Comments 

about this draft will be considered by 

FDA and the Safety Expert Working 

Group. 

The draft guidance provides guidance 

on optimizing the standard genetic 

toxicology battery for the prediction of 

potential human risks, and on 

interpreting the results. The ultimate 

goal of this guidance is to improve risk 

characterization for carcinogenic effects 

induced by changes in the genetic 

material. The draft guidance is intended 

to help facilitate drug development 

programs, ensure patient safety, and 

reduce animal usage. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the agency’s current thinking 

on this topic. 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. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding the draft guidance. 

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. 

Please note that on January 15, 2008, 

the FDA Division of Dockets 

Management Web site transitioned to 

the Federal Dockets Management 

System (FDMS). FDMS is a 

Government-wide, electronic docket 

management system. Electronic 

comments or submissions will be 

accepted by FDA through FDMS only. 

III. Electronic Access 

Persons with access to the Internet 

may obtain the document at http:// 

www.fda.gov/ohrms/dockets/ 

default.htm, http://www.fda.gov/cder/ 

guidance/index.htm, or http:// 

www.fda.gov/cber/publications.htm. 

Dated: March 21, 2008. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. 08–1076 Filed 3–21–08; 3:05 pm] 

BILLING CODE 4160–01–S 

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. 

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: 

Tammie.bell@fda.hhs.gov 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 


pwalker on PROD1PC71 with NOTICES
16026 Federal Register / Vol. 73, No. 59 / Wednesday, March 26, 2008 / Notices 

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/ 

ICHl20080404.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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Substance Abuse and Mental Health 

Services Administration 

Fiscal Year (FY) 2008 Funding 

Opportunity 

AGENCY: Substance Abuse and Mental 

Health Services Administration, HHS. 

ACTION: Notice of intent to award a 

Single Source Grant to the American 

Society of Addiction Medicine (ASAM). 

SUMMARY: This notice is to inform the 

public that the Substance Abuse and 

Mental Health Services Administration 

(SAMHSA) intends to award 

approximately $500,000 (total costs) per 

year for up to three years to the 

American Society of Addiction 

Medicine (ASAM). This is not a formal 

request for applications. Assistance will 

be provided only to the American 

Society of Addiction Medicine (ASAM) 

based on the receipt of a satisfactory 

application that is approved by an 

independent review group. 

Funding Opportunity Title: TI–08–

014. 

Catalog of Federal Domestic 

Assistance (CFDA) Number: 93.243. 

Authority: Section 509 of the Public 

Health Service Act, as amended. 

Justification: Only the American 

Society of Addiction Medicine (ASAM) 

is eligible to apply. The Substance 

Abuse and Mental Health Services 

Administration (SAMHSA) is seeking to 

award a single source grant to the 

American Society of Addiction 

Medicine (ASAM) to establish a 

national mentoring network offering 

support (clinical updates, evidencebased outcomes and training) free of 

charge to physicians and other medical 

professionals in the appropriate use of 

methadone for the treatment of chronic 

pain and opioid addiction. SAMHSA is 

responsible for certifying over 1,000 

Opioid Treatment Programs (OTPs) that 

use methadone and buprenorphine in 

the treatment of opioid addiction. This 

initiative will help address the nation’s 

rise in methadone-associated deaths that 

has been spurred by misuse/abuse and 

fatal drug interactions involving 

methadone. 

According to the National Center for 

Health Statistics (NCHS), methadone 

poisoning deaths nationwide increased 

390% from 786 deaths in 1999 to 3,849 

deaths in 2004, and on going data 

indicate that the number of deaths in 

many states continued to increase in 

2005 and 2006. Thus, prompt and direct 

implementation of this cooperative 

agreement is necessary to help ensure 

public health and safety. 


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