\\CDS018\CDERGUID\FSTUD.DOC

Guidance for Industry

Acceptance of Foreign

Clinical Studies

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

Center for Devices and Radiological Health (CDRH)

Clinical Medical

March 2001
Guidance for Industry

Acceptance of Foreign

Clinical Studies

Additional copies are available from:

Office of Training and Communication

Division of Drug Information HFD-240

Center for Drug Evaluation and Research

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

(Tel) 301-827-4573

http://www.fda.gov/cder/guidance/index.htm

or

 Office of Communication, Training and

Manufacturers Assistance, HFM-40

Center for Biologics Evaluation and Research

 Food and Drug Administration

1401 Rockville Pike, Rockville, MD 20852-1448

 http://www.fda.gov/cber/guidelines.htm

Fax: 1-888-CBERFAX or 301-827-3844

Phone: the Voice Information System at 800-835-4709 or 301-827-1800

or

Division of Small Manufacturers Assistance, HFZ-220

Center for Devices and Radiological Health

Food and Drug Administration

1350 Piccard Dr.

Rockville, MD 20850

Fax: 301-443-8818

http://www.fda.gov/cdrh

Clinical Medical

March 2001
1

Guidance for Industry

Acceptance of Foreign Clinical Studies

I. INTRODUCTION

Food and Drug Administration (FDA) regulations permit the acceptance of foreign

clinical studies in support of an application for marketing approval of a human drug,

biological product, or device if certain conditions are met. Foreign studies performed

under an investigational new drug application (IND) or investigational device exemption

(IDE) must meet the same requirements of 21 CFR Part 312 or 21 CFR Part 812,

respectively, that apply to U.S. studies conducted under an IND or IDE.

Under 21 CFR 312.120(c)(1), FDA will accept a foreign clinical study not conducted

under an IND only if the study conforms to the ethical principles contained in the

Declaration of Helsinki (Declaration), as set out in 21 CFR 312.120(c)(4), incorporating

the 1989 version of the Declaration, or with the laws and regulations of the country in

which the research was conducted, whichever provides greater protection of the human

subjects.

FDA issued 21 CFR 814.15(a) and (b), a similar regulation applicable to devices, in

1986, when the 1983 version of the Declaration was in effect.1 Under 21 CFR

814.15(b), FDA will accept a foreign clinical study involving a medical device that is not

subject to an IDE only if the study conforms to the ethical principles contained in the

1983 version of the Declaration or with the laws and regulations of the country in which

the research was conducted, whichever provides greater protection of the human

subjects.

 

1

 The 1983 and 1989 versions differ in one respect. Both versions state that the design and

performance of each experimental procedure involving human subjects should be clearly formulated in an

experimental protocol, which should be transmitted for consideration, comment, and guidance to a

specially appointed committee. However, the 1989 version qualifies the principle by stating that the

specially appointed committee should be “independent of the investigator and the sponsor provided that

this independent committee is in conformity with the laws and regulations of the country in which the

research experiment is performed.”

This guidance represents the Food and Drug Administration's (FDA'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.
2

In October 2000, the World Medical Association revised the Declaration. FDA has not

taken action to incorporate those revisions into its regulations. FDA is making available

this guidance document to clarify that the action of the World Medical Association did

not change FDA regulations.

II. DECLARATION OF HELSINKI

The World Medical Association first adopted the Declaration in 1964 and, subsequently,

has revised the document five times.

It is FDA’s responsibility to define the conditions under which it will consider foreign

clinical studies to be acceptable under the standards imposed by the United States laws

and regulations. In carrying out that responsibility, in 1975 FDA incorporated the 1964

Declaration in its regulation governing investigational drug trials conducted in non-U.S.

countries. The agency amended the regulation in 1981 to replace the 1964 Declaration

with the 1975 version, and again in 1991 to replace the 1975 Declaration with the 1989

version.2 FDA has repeatedly considered amendments to its regulations governing

foreign clinical studies not conducted under an IND. Each time, FDA has incorporated

amendments only after carefully considering the impact of the amendment and revising

its regulations.

3

 FDA has not amended 21 CFR 312.120 or 21 CFR 814.15 to

incorporate the 2000 amendments to the Declaration recently issued by the World

Medical Association.

FDA is currently reviewing its regulations pertaining to the acceptance of foreign clinical

studies, to determine if it should revise those regulations to incorporate new or modified

standards or requirements.

 

2

 46 Fed Reg. 8942 (January 27, 1981); 56 Fed. Reg. 22113 (May 14, 1991). 3

 FDA has not amended its regulation governing investigational device trials conducted in non-U.S.

countries to incorporate a different version of the Declaration.