Federal Register / Vol. 62, No. 222 / Tuesday, November 18, 1997 / Notices 61513

minimum requirements specified by the

Secretary and to give full faith and

credit to such an affidavit signed in any

other State according to its procedures.

The Department established a task

group composed of Federal and State

staff to recommend minimum data

elements for all State paternity

acknowledgment affidavits. The

minimum data elements were crafted to

balance the need for a tool for collecting

information necessary to the

establishment of a child support order

and the need for a user-friendly form

that addresses only the data necessary to

establish legal paternity. The minimum

data elements are: The current full

name, social security number and date

of birth of mother, father, and child;

address of mother and father, birthplace

of child; an explanation of the legal

consequences of signing the affidavit; a

statement indicating both parents

understand their rights, responsibilities,

alternatives and the consequences of

signing the affidavit; the place the

affidavit was completed; and signature

lines for mother, father and witnesses or

notaries.

Respondents: Individuals and

Households; Not-for-Profit Institutions;

and State, Local or Tribal Govt.

ANNUAL BURDEN ESTIMATES

Instrument Number of respondents

Number of responses per

respondent

Average burden hours per

response

Total burden

hours

Affidavits ........................................................................................................... 2,000,000 .2243 .166 74,468

Estimated Total Annual Burden

Hours: 74,468.

Additional Information: Copies of the

proposed collection may be obtained by

writing to The Administration for

Children and Families, Office of

Information Services, Division of

Information Resource Management

Services, 370 L’Enfant Promenade, S.W.,

Washington, D.C. 20447, Attn: ACF

Reports Clearance Officer.

OMB Comment: OMB is required to

make a decision concerning the

collection of information between 30

and 60 days after publication of this

document in the Federal Register.

Therefore, a comment is best assured of

having its full effect if OMB receives it

within 30 days of publication. Written

comments and recommendations for the

proposed information collection should

be sent directly to the following: Office

of Management and Budget, Paperwork

Reduction Project, 725 17th Street,

N.W., Washington, D.C. 20503, Attn:

Ms. Wendy Taylor.

Dated: November 12, 1997.

Bob Sargis,

Acting Reports Clearance Officer.

[FR Doc. 97–30220 Filed 11–17–97; 8:45 am]

BILLING CODE 4184–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97D–0444]

International Conference on

Harmonisation; Draft Guidance on the

Duration of Chronic Toxicity Testing in

Animals (Rodent and Nonrodent

Toxicity Testing); Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is publishing a

draft guidance entitled ‘‘S4A Duration

of Chronic Toxicity Testing in Animals

(Rodent and Nonrodent Toxicity

Testing).’’ The draft guidance was

prepared under the auspices of the

International Conference on

Harmonisation of Technical

Requirements for Registration of

Pharmaceuticals for Human Use (ICH).

The draft guidance is intended to

provide guidance on the duration of

chronic toxicity testing in rodents and

nonrodents as part of the safety

evaluation of a drug product.

DATES: Written comments by January 20,

1998.

ADDRESSES: Submit written comments

on the draft guidance to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 12420

Parklawn Dr., rm. 1–23, Rockville, MD

20857. Copies of the draft guidance are

available from the Drug Information

Branch (HFD–210), Center for Drug

Evaluation and Research, Food and

Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–827–

4573.

FOR FURTHER INFORMATION CONTACT:

Regarding the guidance: Joseph J.

DeGeorge, Center for Drug

Evaluation and Research (HFD–24),

Food and Drug Administration,

5600 Fishers Lane, Rockville, MD

20857, 301–594–6758.

Regarding the ICH: Janet J. Showalter,

Office of Health Affairs (HFY–20),

Food and Drug Administration,

5600 Fishers Lane, Rockville, MD

20857, 301–827–0864.

SUPPLEMENTARY INFORMATION: 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 drug development

among regulatory agencies.

ICH was organized to provide an

opportunity for tripartite harmonization

initiatives to be developed with input

from both regulatory and industry

representatives. FDA also seeks input

from consumer representatives and

others. ICH is concerned with

harmonization of technical

requirements for the registration of

pharmaceutical products 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 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

sponsors and the IFPMA, as well as

observers from the World Health

Organization, the Canadian Health

Protection Branch, and the European

Free Trade Area.

In July 1997, the ICH Steering

Committee agreed that a draft guidance

entitled ‘‘S4A Duration of Chronic
61514 Federal Register / Vol. 62, No. 222 / Tuesday, November 18, 1997 / Notices

Toxicity Testing in Animals (Rodent

and Nonrodent Toxicity Testing)’’

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.

In accordance with FDA’s Good

Guidance Practices (62 FR 8961,

February 27, 1997), this document has

been designated a guidance, rather than

a guideline.

The draft document provides

guidance on the duration of chronic

toxicity testing in rodents and

nonrodents as part of the safety

evaluation of a drug product. The draft

guidance is intended to help eliminate

or reduce the need for pharmaceutical

companies to duplicate testing during

the development of new drug products.

FDA has proposed draft guidance

before on chronic toxicity testing. In the

Federal Register of April 15, 1992 (57

FR 13105), FDA announced the

availability of a proposed approach to

toxicity testing, including long-term

toxicity studies. The new ICH draft

guidance published here reflects a

change in recommended testing in

nonrodents based on an evaluation of

findings from chronic toxicity studies.

The evaluation report is available in

Docket No. 97D–0444. The agency

requests comments on the draft

guidance and on specific classes of

pharmaceuticals for which either

shorter or longer durations of testing in

nonrodents should be considered as

general exceptions to the duration

recommended in the draft guidance. It

would be helpful if the scientific basis

for comments addressing ‘‘general

exceptions’’ were also provided. Once

this guidance is finalized, it will

supersede the 1992 proposed guidance

(57 FR 13105).

Other portions of the proposed

approach to toxicity testing announced

in the Federal Register of April 15,

1992, have been superseded by draft

and finalized FDA and ICH guidances as

follows:

TABLE 1.—1992 DRAFT PROPOSED GUIDANCE

Topic Superseded by

Single Dose (Acute) Toxicity Studies Guidance for Industry on Single Dose Acute Toxicity Testing for Pharmaceuticals, PT 1, (61 FR 43934, August 26, 1996)

Reproductive and Developmental Studies Detection of Toxicity to Reproduction for Medicinal Products, ICH S5A,

(59 FR 48746, September 22, 1994)

Detection of Toxicity to Reproduction for Medicinal Products: Addendum on Toxicity to Male Fertility, ICH S5B (61 FR 15360, April 5,

1996)

Carcinogenicity Studies (Dose Selection) Dose Selection for Carcinogenicity Studies of Pharmaceuticals, ICH

S1C, (60 FR 11278, March 1, 1995)

Dose Selection for Carcinogenicity Studies of Pharmaceuticals—Addition of the Limit Dose and Related Notes, Draft ICH S1C(R) (62 FR

15715, April 2, 1997)

Timing and Duration Nonclinical Studies for the Conduct of Human Clinical Trials for Pharmaceuticals, Draft ICH M3 (62 FR 24320, May 2, 1997)

This draft guidance represents the

agency’s current thinking on the

duration of chronic toxicity testing in

animals (rodent and nonrodent toxicity

testing). 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

January 20, 1998, submit to the Dockets

Management Branch (address above)

written comments on the draft guidance.

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 guidance 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 guidance is available on

the Internet using the World Wide Web

(WWW) ‘‘http://www.fda.gov/cder/

guidance.htm’’.

The text of the draft guidance follows:

S4A Duration of Chronic Toxicity Testing in

Animals (Rodent and Nonrodent Toxicity

Testing)

Objective:

The objective of this guidance is to set out

the considerations that apply to chronic

toxicity testing in rodents and nonrodents as

part of the safety evaluation of a medicinal

product. Since guidance is not legally

binding, an applicant may submit

justification for an alternative approach.

Scope:

This guidance has been prepared for the

development of medicinal products with the

exception of those already covered by ‘‘Safety

Studies for Biotechnological Products,’’ e.g.,

monoclonal antibodies, recombinant DNA

proteins.

Background:

During the first International Conference

on Harmonisation in 1991, the practices for

the testing of chronic toxicity in the three

regions (the European Union, Japan, and the

United States) were reviewed. Arising from

this, it emerged that there was a scientific

consensus on the approach for chronic

testing in rodents, supporting the

harmonized duration of testing of 6 months.

However, for chronic toxicity testing in

nonrodents, there were different approaches

to the duration of testing.

The lack of harmonized duration led to the

need for pharmaceutical companies to

perform partially duplicative studies for both

6 and 12 months duration when developing

new medicinal products. As the objective of

ICH is to reduce or eliminate the need to

duplicate testing during development of

medicinal products and to ensure a more

economical use of material, animal, and

human resources, while at the same time

maintaining safeguards to protect public

health, further scientific evaluation was

undertaken.

Each of the regulatory authorities in the

European Union, Japan, and the United

States undertook a review to determine

whether a single duration for chronic toxicity

testing in nonrodents could be identified.

From this analysis, it emerged that in 16

cases, a more detailed evaluation of 6 versus

12 months data should be undertaken.

This evaluation was conducted as a joint

exercise by the competent authorities in the

three regions.

In some of the cases analyzed at the

tripartite meetings, there were no additional

findings at 12 months. For some other cases,

there was not complete agreement among the

regulators with respect to the comparability

in study design and conduct to allow

assessment of whether there were differences

in the findings at 6 and 12 months due to

duration of treatment alone.
Federal Register / Vol. 62, No. 222 / Tuesday, November 18, 1997 / Notices 61515

In a number of cases there were findings

observed by 12 months, but not by 6 months.

It was concluded that these would, or could,

have been detected in a study of 9 months

duration. Varying degrees of concern for the

differences in findings detected between the

studies of different durations were expressed.

An agreement on the clinical relevance of

these findings could not be reached.

Studies of 12 months duration are usually

not necessary and studies of shorter than 9

months duration may be sufficient.

In the European Union, studies of 6

months duration in nonrodents are

acceptable according to Council Directive 75/

318/EEC, as amended. To avoid duplication,

where studies with a longer duration have

been conducted, it would not be necessary to

conduct a study of 6 months.

Guidance on duration of chronic toxicity

testing for tripartite development plan:

Arising from the extensive analysis and

review of the above mentioned data in

nonrodents and based upon the

achievements of ICH 1 for testing in rodents,

and so as to avoid duplication and to follow

a single development plan for chronic

toxicity testing of new medicinal products,

the following studies are considered

acceptable for submission in the three

regions:

(1) Rodents: a study of 6 months duration;

(2) Nonrodents: a study of 9 months

duration.

Dated: November 12, 1997.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 97–30273 Filed 11–17–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97D–0113]

International Conference on

Harmonisation; Guidance on

Preclinical Safety Evaluation of

Biotechnology-Derived

Pharmaceuticals; Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is publishing a

guidance entitled ‘‘S6 Preclinical Safety

Evaluation of Biotechnology-Derived

Pharmaceuticals.’’ The guidance was

prepared under the auspices of the

International Conference on

Harmonisation of Technical

Requirements for Registration of

Pharmaceuticals for Human Use (ICH).

The guidance is intended to provide

general principles for designing

scientifically acceptable preclinical

safety evaluation programs for

biopharmaceuticals.

DATES: Effective November 18, 1997.

Submit written comments at any time.

ADDRESSES: Submit written comments

on the guidance to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 12420

Parklawn Dr., rm. 1–23, Rockville, MD

20857. Copies of the guidance are

available from the Drug Information

Branch (HFD–210), Center for Drug

Evaluation and Research, Food and

Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–827–

4573. Single copies of the draft guidance

may be obtained by mail from the Office

of Communication, Training and

Manufacturers Assistance (HFM–40),

Center for Biologics Evaluation and

Research (CBER), or by calling the CBER

Voice Information System at 1–800–

835–4709 or 301–827–1800. Copies may

be obtained from CBER’s Fax

Information System at 1–888–CBER–

FAX or 301–827–3844.

FOR FURTHER INFORMATION CONTACT:

Regarding the guidance: Joy A.

Cavagnaro, Center for Biologics

Evaluation and Research (HFM–5),

Food and Drug Administration,

1401 Rockville Pike, Rockville, MD

20852, 301–827–0379.

Regarding the ICH: Janet J. Showalter,

Office of Health Affairs (HFY–20),

Food and Drug Administration,

5600 Fishers Lane, Rockville, MD

20857, 301–827–0864.

SUPPLEMENTARY INFORMATION: 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 drug development

among regulatory agencies.

ICH was organized to provide an

opportunity for tripartite harmonization

initiatives to be developed with input

from both regulatory and industry

representatives. FDA also seeks input

from consumer representatives and

others. ICH is concerned with

harmonization of technical

requirements for the registration of

pharmaceutical products 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 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

sponsors and the IFPMA, as well as

observers from the World Health

Organization, the Canadian Health

Protection Branch, and the European

Free Trade Area.

In the Federal Register of April 4,

1997 (62 FR 16438), FDA published a

draft tripartite guideline entitled

‘‘Preclinical Testing of BiotechnologyDerived Pharmaceuticals’’ (S6). The

notice gave interested persons an

opportunity to submit comments by

June 3, 1997.

After consideration of the comments

received and revisions to the guidance,

a final draft of the guidance was

submitted to the ICH Steering

Committee and endorsed by the three

participating regulatory agencies on July

16, 1997.

In accordance with FDA’s Good

Guidance Practices (62 FR 8961,

February 27, 1997), this document has

been designated a guidance, rather than

a guideline.

The guidance recommends a basic

framework for the preclinical safety

evaluation of biotechnology-derived

pharmaceuticals. Adherence to the

principles presented in the guidance

will allow for improvement in the

quality and consistency of preclinical

safety data supporting the development

of biopharmaceuticals.

This guidance represents the agency’s

current thinking on preclinical safety

evaluation of biotechnology-derived

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.

As with all of FDA’s guidances, the

public is encouraged to submit written

comments with new data or other new

information pertinent to this guidance.

The comments in the docket will be

periodically reviewed, and, where

appropriate, the guidance will be

amended. The public will be notified of

any such amendments through a notice

in the Federal Register.