15716 Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices

pharmaceuticals. 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 statute,

regulations, or both.

Interested persons may, on or before

June 2, 1997, submit written comments

on the draft guideline to the Dockets

Management Branch (address above).

Two copies of any comments are to be

submitted, except that individuals may

submit one copy. Comments are to be

identified with the docket number

found in brackets in the heading of this

document. The draft guideline and

received comments may be seen in the

office above between 9 a.m. and 4 p.m.,

Monday through Friday. An electronic

version of this draft guideline is

available via the Internet using the

World Wide Web (WWW). To connect

to the CDER home page, type http://

www.fda.gov/cder and go to the

‘‘Regulatory Guidance’’ section.

The text of the draft guideline follows:

Addendum to ‘‘Dose Selection for

Carcinogenicity Studies of Pharmaceuticals’’

Limit Dose

Under a defined set of conditions, it would

be considered acceptable to limit the high

dose administered for nongenotoxic

pharmaceuticals in long-term carcinogenicity

testing to a maximum, e.g., 1000 mg/kg/day

in rats. This approach is only considered

appropriate where the other accepted

methods of dose selection have been

evaluated and each has been considered not

applicable based on scientific justification.

Use of this alternative is considered

appropriate when:

1. Neither a toxicity-based endpoint (MTD)

nor a pharmacodynamic-based dose selection

endpoint can be achieved; and

2. Determination of pharmacokinetic

parameters needed to apply pharmacokinetic

endpoints (the 25-fold ratio of rodent to

human AUC or saturation of absorption) is

not feasible or is inappropriate due to

scientific or technical limitations.

Under such circumstances, it would be

considered acceptable to use the maximum

feasible dose (e.g., 5 percent of diet) for

selection of the high dose. However, if in

addition to meeting the criteria 1. and 2.

above, the dose of the pharmaceutical for use

in humans is 50 mg/day, a ‘‘limit dose’’ of

1000 mg/kg/day is considered acceptable for

high dose selection (see NOTE). This

endpoint is consistent with the principles set

forth in the paragraphs on pharmacokinetic

endpoints, achieving approximately the same

margin of safety as specified there based on

a mg/m2 basis. For those pharmaceuticals

used at maximum daily human doses higher

or lower than 50 mg/day it is considered

acceptable to limit the top dose in a rat

carcinogenicity study proportionally.

NOTE

The dose of 50 mg/day in humans (leading

to 1 mg/kg on an assumed human weight of

50 kg) is an approximate calculation based

upon the following: A conversion from mg/

kg to mg/m2, the AUC ratio of 25, and a

multiplication factor of 6 to account for the

variance (approximately 95 percent

confidence interval) for estimation of the

AUC ratio from mg/m2 ratio (rodent to

human) (see, for the data, Contrera, et al.,

Journal of the American College of

Toxicology, 14:1–10, 1995). A similar

rationale and calculation can be applied for

other rodent species.

Dated: March 25, 1997.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97–8353 Filed 4–1–97; 8:45 am]

BILLING CODE 4160–01–F

National Institutes of Health

National Center for Research

Resources; Closed Meetings

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following

National Center for Research Resources

Special Emphasis Panel (SEP) meetings:

Name of SEP: General Clinical Research

Centers.

Date: May 13–14, 1997.

Time: 8 a.m.

Place: Holiday Inn Iowa City, Johnson 1 &

2 Conference Room, 210 South Dubuque

Street, Iowa City, IA 52240, (319) 337–4058.

Contact Person: Dr. Bela Gulyas, Scientific

Review Administrator, 6705 Rockledge Drive,

MSC 7965, Room 6018, Bethesda, MD 20892–

7965, (301) 435–0811.

Name of SEP: Biomedical Research

Technology.

Date: May 27–29, 1997.

Time: 8 a.m.

Place: Doubletree Hotel, Conference

Rooms—Twinbrook, Montrose, and

Parklawn, 1750 Rockville Pike, Rockville,

MD 20852, (301) 468–1100.

Contact Person: Dr. Sharon Moss,

Scientific Review Administrator, 6705

Rockledge Drive, MSC 7965, Room 6018,

Bethesda, MD 20892–7965, (301) 435–0811.

Purpose/Agenda: To evaluate and review

grant applications.

The meetings will be closed in accordance

with the provisions set forth in sections

552b(c)(4) and 552b(c)(6), Title 5, U.S.C.

Applications and/or proposals and the

discussions could reveal confidential trade

secrets or commercial property such as

patentable material and personal information

concerning individuals associated with the

applications and/or proposals, the disclosure

of which would constitute a clearly

unwarranted invasion of personal privacy.

(Catalog of Federal Domestic Assistance

Program No. 93.371, Biomedical Research

Technology; 93.333, Clinical Research,

National Institutes of Health, HHS)

Dated: March 27, 1997.

LaVerne Y. Stringfield,

Committee Management Officer, National

Institutes of Health.

[FR Doc. 97–8294 Filed 4–1–97; 8:45 am]

BILLING CODE 4140–01–M

National Center for Research

Resources; Closed Meeting

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following

meeting:

Name of Committee: Scientific and

Technical Review Board on Biomedical and

Behavioral Research Facilities.

Dates of Meeting: May 28–30, 1997.

Time: 8 a.m.–until adjournment.

Place of Meeting: Doubletree Hotel,

Halpine Room, 1750 Rockville Pike,

Rockville, MD 20892, Tel: (301) 468–1100.

Scientific Review Administrator: Dr. D. G.

Patel, National Institutes of Health, 1

Rockledge Center, Room 6018, 6705

Rockledge Drive, MSC 7965, Bethesda, MD

20892–7965, Telephone: (301) 435–0822.

Purpose/Agenda: To review and evaluate

grant applications. The meeting will be

closed in accordance with the provisions set

forth in sections 552b(c)(4) and 552b(c)(6),

Title 5, U.S.C. Applications and/or proposals

and the discussions could reveal confidential

trade secrets or commercial property such as

patentable material and personal information

concerning individuals associated with the

applications and/or proposals, the disclosure

of which would constitute a clearly

unwarranted invasion of personal privacy.

(Catalog of Federal Domestic Assistance

Program No. 93.167 Research Facilities

Improvement Program, National Institutes of

Health, HHS)

Dated: March 27, 1997.

LaVerne Y. Stringfield,

Committee Management Officer, National

Institutes of Health.

[FR Doc. 97–8297 Filed 4–1–97; 8:45 am]

BILLING CODE 4140–01–M

National Institute of Mental Health;

Closed Meetings

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following

meetings of the National Institute of

Mental Health Special Emphasis Panel:

Agenda/Purpose: To review and evaluate

grant applications.

Committee Name: National Institute of

Mental Health Special Emphasis Panel.

Date: April 3, 1997.

Time: 3 p.m.

Place: Parklawn, Room 9C–26, 5600

Fishers Lane, Rockville, MD 20857.

Contact Person: Phyllis D. Artis, Parklawn,

Room 9C–26, 5600 Fishers Lane, Rockville,

MD 20857, Telephone: 301, 443–6470.
Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices 15717

Committee Name: National Institute of

Mental Health Special Emphasis Panel.

Date: April 9, 1997.

Time: 4 p.m.

Place: Parklawn, Room 9C–18, 5600

Fishers Lane, Rockville, MD 20857.

Contact Person: Gloria B. Levin, Parklawn,

Room 9C–18, 5600 Fishers Lane, Rockville,

MD 20857, Telephone: 301, 443–1367.

The meetings will be closed in accordance

with the provisions set forth in sections

552b(c)(4) and 552b(c)(6), Title 5, U.S.C.

Applications and/or proposals and the

discussions could reveal confidential trade

secrets or commercial property such as

patentable material and personal information

concerning individuals associated with the

applications and/or proposals, the disclosure

of which would constitute a clearly

unwarranted invasion of personal privacy.

This notice is being published less than

fifteen days prior to the meetings due to the

urgent need to meet timing limitations

imposed by the review and funding cycle.

(Catalog of Federal Domestic Assistance

Program Numbers 93.242, 93.281, 93.282)

Dated: March 27, 1997.

LaVerne Y. Stringfield,

Committee Management Officer, National

Institutes of Health.

[FR Doc. 97–8293 Filed 4–1–97; 8:45 am]

BILLING CODE 4140–01–M

National Institute of Environmental

Health Sciences; Closed Meetings

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following

National Institute of Environmental

Health Sciences Special Emphasis Panel

(SEP) meetings:

Name of SEP: Review of a Center for

Environmental and Rural Health.

Date: May 5–7, 1997.

Time: 7 P.M.

Place: College Station Hilton and

Conference Center, 801 University Drive,

College Station, Texas 77840–2116.

Contact Person: Dr. Linda K. Bass, National

Institute of Environmental Health Sciences,

P.O. Box 12233, MD 17–09, Research

Triangle Park, NC 27709, (919) 541–1307.

Purpose/Agenda: To review and evaluate

grant applications.

Name of SEP: Review of a Research Center

in Environmental Health Sciences.

Date: June 10–12, 1997.

Time: 7 P.M.

Place: Hyatt Regency New Brunswick, New

Brunswick, New Jersey 08901.

Contact Person: Dr. Ethel B. Jackson,

National Institute of Environmental Health

Sciences, P.O. Box 12233, MD 17–09,

Research Triangle Park, NC 27709, (919) 541–

7826.

Purpose/Agenda: To review and evaluate

grant applications.

These meetings will be closed in

accordance with the provisions set forth in

sections 552b(c)(4) and 552b(c)(6), Title 5,

U.S.C. Applications and the discussions

could reveal confidential trade secrets or

commercial property such as patentable

material and personal information

concerning individuals associated with the

applications, the disclosure of which would

constitute a clearly unwarranted invasion of

personal privacy.

(Catalog of Federal Domestic Assistance

Programs Nos. 93.113, Biological Response to

Environmental Agents; 93.114, Applied

Toxicological Research and Testing; 93.115,

Biometry and Risk Estimation; 93.894,

Resource and Manpower Development,

National Institutes of Health)

Dated: March 27, 1997.

LaVerne Y. Stringfield,

Committee Management Officer, National

Institutes of Health.

[FR Doc. 97–8295 Filed 4–1–97; 8:45 am]

BILLING CODE 4140–01–M

National Institute of Health

National Institute of Mental Health;

Closed Meetings

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following

meetings of the National Institute of

Mental Health Special Emphasis Panel:

Agenda/Purpose: To review and evaluate

grant applications.

Committee Name: National Institute of

Mental Special Emphasis Panel.

Date: April 8, 1997.

Time: 1 p.m.

Place: Parklawn, Room 9C–18, 5600

Fishers Lane, Rockville, MD 20857.

Contact Person: Gloria B. Levin, Parklawn,

Room 9C–18, 5600 Fishers Lane, Rockville,

MD 20857, Telephone: 301–443–1367.

Committee Name: National Institute of

Mental Special Emphasis Panel.

Date: April 15, 1997.

Time: 1 p.m.

Place: Parklawn, Room 9C–18, 5600

Fishers Lane, Rockville, MD 20857.

Contact Person: Gloria B. Levin, Parklawn,

Room 9C–18, 5600 Fishers Lane, Rockville,

MD 20857, Telephone: 301–443–1367.

The meetings will be closed in accordance

with the provisions set forth in sections

552b(c)(4) and 552b(c)(6), Title 5, U.S.C.

Applications and/or proposals and the

discussions could reveal confidential trade

secrets or commercial property such as

patentable material and personal information

concerning individuals associated with the

applications and/or proposals, the disclosure

of which would constitute a clearly

unwarranted invasion of personal privacy.

This notice is being published less than

fifteen days prior to the meetings due to the

urgent need to meet timing limitations

imposed by the review and funding cycle.

(Catalog of Federal Domestic Assistance

Program Numbers 93.242, 93.281, 93.282.)

Dated: March 27, 1997.

LaVerne Y. Stringfield,

Committee Management Officer, National

Institutes of Health.

[FR Doc. 97–8296 Filed 4–1–97; 8:45 am]

BILLING CODE 4140–01–M

National Institutes of Health

National Institute on Aging; Closed

Meetings

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following

National Institute on Aging Special

Emphasis Panel meetings:

Name of SEP: Cross National Conference

on Health and Retirement Data

(Teleconference).

Date of Meeting: April 11, 1997.

Time of Meeting: 1:30 p.m. to adjournment.

Place of Meeting: National Institute on

Aging, Gateway Building, Room 2C212, 7201

Wisconsin Avenue, Bethesda, Maryland

20892.

Purpose/Agenda: To evaluate and review a

conference grant application.

Contact Person: Dr. Mary Ann Guadagno,

Scientific Review Administrator, Gateway

Building, Room 2C212, National Institutes of

Health, Bethesda, Maryland 20892–9205,

(301) 496–9666.

This notice is being published less

than 15 days prior to the above meeting

due to the urgent need to meet timing

limitations imposed by the review and

funding cycle.

Name of SEP: Third Colorado Conference

on Elderly Migration (Teleconference).

Date of Meeting: April 17, 1997.

Time of Meeting: 1:30 p.m. to adjournment.

Place of Meeting: National Institute on

Aging, Gateway Building, 7201 Wisconsin

Avenue, Suite 2C212, Bethesda, Maryland

20892.

Purpose/Agenda: To evaluate and review a

conference grant application.

Contact Person: Dr. Mary Ann Guadagno,

Scientific Review Administrator, Gateway

Building, Room 2C212, National Institutes of

Health, Bethesda, Maryland 20892–9205,

(301) 496–9666.

Name of SEP: The Development and

Maintenance of Aged, Calorie-Restricted

Mice and Rates. (Teleconference).

Date of Meeting: April 28, 1997.

Time of Meeting: 1:00 p.m. to adjournment.

Place of Meeting: National Institute on

Aging, Gateway Building, 7201 Wisconsin

Avenue, Suite 2C212, Bethesda, Maryland

20892.

Purpose/Agenda: To evaluate and review a

contract proposal.

Contact Person: Dr. Arthur D. Schaerdel,

Scientific Review Administrator, Gateway

Building, Room 2C212, National Institutes of

Health, Bethesda, Maryland 20892–9205,

(301) 496–9666.

These meetings will be closed in

accordance with the provisions set forth in