Guidance for Industry: Exports Under the FDA Export Reform and Enhancement Act of 1996 : Guidance for Industry

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Guidance for Industry:
Exports Under the FDA Export
Reform and Enhancement Act of 1996
Submit written comments at any time. Submit comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. All comments should be identified with the Docket No. 1998D-0307.
For questions regarding this document contact the Center for Veterinary Medicine at 301-594-
1785, Center for Biologics Evaluation and Research at 301-827-6201, Center for Devices and
Radiological Health at 301-594-4699, Center for Drug Evaluation and Research at 301-827-
8930, or Center for Food Safety and Applied Nutrition at 1-888-723-3366
Additional copies are available from:
Office of International Programs (HFG-1)
Food and Drug Administration
5600 Fishers Lane,
Rockville, MD 20857
(Tel) 301-827-4480
http://www.fda.gov /ohrms/dockets/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Office of International Programs
July 23, 2007

Table of Contents
I. Introduction ...........................................................................................................1
II. 	Terms Used in This Guidance ............................................................................4
III. 	Quick Guide....................................................................................................... 6
IV. 	Statutory Background ....................................................................................... 10
A. 	Historical Background - Exports of Drugs and Biological Products
That May Not Be Sold in the United States ..................................... 10
B. 	Historical Background - Exports of Animal Drugs That May
Not Be Sold in the United States .....................................................13
C. 	Historical Background - Exports of Devices That May Not Be
Sold in the United States ..................................................................14
D. 	Enactment of the FDA Export Reform and Enhancement
Act of 1996 ..................................................................................... 15
V. General Requirements for Products Exported Under Section 801(e) (1)
of the Act ...................................................................................................... 18
A. 	Summary of Section 801(e)(1) of the Act......................................... 18
B. 	Determining Compliance with Section 801(e)(1) of the Act............ 18
1. 	Meeting a Foreign Purchaser’s Specifications...................... 19
2. 	Not in Conflict with the Laws of the Importing Country..... 20
3. 	Shipping Package Labeling Showing that the Product is
Intended for Export............................................................... 29
4. 	Product is Not Sold or Offered for Sale
in the United States............................................................... 21
C 	Special Restrictions on Animal Drugs ............................................. 22
D. 	Special Requirements for Certain Devices ................ ...................... 22
E. 	Special Requirements for Partially Processed Biological Products. 24
1. 	What Constitutes a
Partially Processed Biological Product? .............................. 25
2. 	cGMP Requirements ............................................................ 25
3. 	Additional Requirements Under Section 351(h) of the
Public Health Service (PHS) Act. .........................................26
VI. 	Labeling Requirements for Drugs and Biological Products Exported Under
Section 801(e) (1) of the Act - Section 801(f) of the Act ..............................28
VII. 	Exports of Unapproved Drugs, Biological Products, and Devices
Under Section 802(b) of the Act .................................................................. 30
A. 	Drugs and Biological Products ......................................................... 30
B. 	Devices ............................................................................................. 31
C. 	Basic Requirements for All Products Exported

Under Section 802 of the Act .......................................................... 31
D. 	Exports of Unapproved New Drugs, Biological Products, and
Devices to a Listed Country - Section 802(b) (1) (A) of the Act ......34
E. 	Expanding the List of Countries in Section 802(b) (1) (A)
of the Act .......................................................................................... 36
F. 	Exports of Unapproved New Drugs and Biological Products to an
Unlisted Country - Section 802(b)(2) and (b)(3) of the Act ............ 36
VIII. 	Exports of Unapproved Drugs and Devices for Investigational Use to Listed
Countries Under Section 802(c) of the Act ................................................. 41
A. 	Historical Background...................................................................... 41
B. 	Impact of the 1996 Amendments on Drug Exports for
Investigational 	Use ........................................................................... 42
C. 	Impact of the 1996 Amendments on Device Exports for
Investigational 	Use ........................................................................... 45
IX. 	Exports of Unapproved Drugs and Devices in Anticipation of
Foreign Approval - Section 802(d) of the Act ............................................. 47
X. Exports of Drugs and Devices for Diagnosing, Preventing, or Treating a
Tropical Disease or a Disease “Not of Significant Prevalence in the
United States” - Section 802(e) of the Act ................................................... 49
XI. 	Export Notification and Recordkeeping Under Section 802(g) of the Act.......51
A. 	The Content of the Simple Notification ........................................... 51
B. 	Where to Send the Simple Notification ........................................... 52
C. 	Recordkeeping ................................................................................. 53
XII. 	For Further Information, Contact .................................................................. 55

Guidance for Industry: Exports Under the FDA Export
Reform and Enhancement Act of 19961
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic and
replaces FDA’s previous guidance on exports entitled, “A Review of FDA’s Implementation of the Drug
Export Amendments of 1986.” It does not create or confer any rights for or on any person and does not
operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the
requirements of the applicable statutes and regulations. If you want to discuss an alternative approach,
contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate
FDA staff, call the appropriate number listed on the title page of this guidance.
I. Introduction
This guidance document summarizes and explains the basic requirements and procedures
under the FDA Export Reform and Enhancement Act of 1996 (Public Law 104-134, as amended
by Public Law 104-180) for exporting human drugs, animal drugs, biological products, devices,
food, food additives, color additives, and dietary supplements that may not be sold or distributed
in the United States. This law amended sections 801 and 802 of the Federal Food, Drug, and
Cosmetic Act (the Act), as well as section 351(h) of the Public Health Service Act, simplifying
the requirements for exporting unapproved human drugs, biological products, and devices. In
addition, the FDA Export Reform and Enhancement Act substantially reduced the requirements
for exporting unapproved new animal drugs and provided a new option for exporting unapproved
devices.
The 1996 Amendments did not change the general export requirements in section
801(e)(1) of the Act with respect to foods or cosmetics. This document provides guidance on
these general export requirements under section 801(e)(1) of the Act for all products that are
1 This guidance has been prepared by the Office of International Programs in the Office of the
Commissioner in cooperation with the Center for Veterinary Medicine, Center for Biologics, Center for Devices and
Radiological Health, Center for Drug Evaluation and Research, and Center for Food Safety and Applied Nutrition at
the Food and Drug Administration.
This guidance document may be supplemented by other guidance documents on specific topics.
1

subject to this provision. Guidance is also provided on the export requirements for unapproved
human drugs, biological products and devices in sections 801 and 802 of the Act resulting from
the 1996 Amendments.
If a product meets the Act’s requirements for sale and distribution in the United States,
the Act has no additional restrictions on its exportation (i.e., sections 801 and 802 of the Act do
not apply to such exports). However, other federal statutes or regulations administered by other
federal agencies (such as the Department of Commerce) may apply.
This guidance document does not address export certificates and any associated fees.
Information on these subjects can be found in FDA’s Compliance Policy Guide 7150.01,
“Certification for Exports” , and FDA’s Guidance for Industry, “FDA Export Certificates”.
This guidance document also does not address the importation and subsequent
exportation of certain articles under section 801(d)(3) and (d)(4) of the Act, which is sometimes
referred to as the “import-for-export” provision. Although the draft guidance document on the
1996 Export Reform and Enhancement Act discussed the importation of certain components,
parts, and accessories of human drugs, biological products, devices, food additives, color
additives, and dietary supplements for further processing or incorporation into products intended
for export, the Public Health Security and Bioterrorism Preparedness and Response Act of 20022
significantly revised section 801(d)(3) of the Act. The revised statutory provision went into
effect on September 9, 2002, and FDA announced, in a September 18, 2002, Federal Register
notice (67 FR 58810), that it had revised the relevant FDA Regulatory Procedures Manual
chapter to incorporate those changes.
Please note that a firm or product may be subject to additional statutory or
regulatory requirements beyond those described in this guidance. For example, a firm may
be subject to the establishment registration requirements under section 510 of the Act (21 U.S.C.
360). Please contact the appropriate FDA center for additional information. Additionally,
exports involving controlled substances may be subject to requirements administered by the
Drug Enforcement Administration. Exports of certain products or exports to specific countries
2 Public Law 107-188, enacted on June 12, 2002.
2

may be subject to licensing and other requirements administered by the Department of
Commerce or the Bureau of the Census.
FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.
3

II. 	Terms Used in This Guidance
This guidance uses the following terms:
“Act” means the Federal Food, Drug, and Cosmetic Act. Citations to specific sections of
the Act will use the numerical sequence specified in the Act rather than the section numbers used
in the United States Code (U.S.C.).
“cGMP” means current good manufacturing practice. For drugs and most biological
products, cGMP regulations can be found at parts 210 and 211 (21 CFR Parts 210 and 211). For
devices and biological products regulated as devices, cGMP regulations (referred to as quality
systems regulations or QSR) can be found at part 820 (21 CFR Part 820). For blood and blood
components, additional regulations can be found at part 606 (21 CFR Part 606).
“FDA” or “agency” means the Food and Drug Administration.
“IDE” means an investigational device exemption application. These are applications
containing requests to use an unapproved device in clinical tests using human subjects. The
regulations are authorized under section 520(g) of the Act (21 U.S.C. 360(g)), and the
implementing regulations can be found at part 812 (21 CFR Part 812).
“IND” means an investigational new drug application. These applications are usually
required for persons who intend to conduct clinical investigations involving products subject to
section 505 of the Act (21 U.S.C. 355) or to the licensure provisions in section 351 of the Public
Health Service Act (42 U.S.C. 262). The IND regulations are authorized by section 505(i) of the
Act and are found at part 312 (21 CFR Part 312).
“1986 Amendments” means the Drug Export Amendments Act of 1986 (Public Law 99-
4

960). The FDA Export Reform and Enhancement Act of 1996 revised or eliminated most
provisions in the 1986 Amendments.
“1996 Amendments” means the FDA Export Reform and Enhancement Act of 1996
(Public Law 104-134 and amended by Public Law 104-180).
“PHS Act” means the Public Health Service Act (42 U.S.C. 201 et seq.). Citations to
specific sections of the PHS Act will use the numbers specified in the PHS Act rather than the
section numbers used in the U.S. Code.
“PMA” means a premarket approval application. This is a marketing application for
certain devices under section 515 of the Act. The PMA regulation is at 21 CFR part 814.
“312 Program” means the regulatory program used by FDA for permitting the
exportation of investigational drugs or biological products for clinical use in foreign countries.
The principal statutory authority for the 312 Program is section 505(i) of the Act, and the
implementing regulation is at 21 CFR § 312.110.
5

III. Quick Guide
The chart below can be used to identify possible export routes for FDA-regulated
products in various circumstances. You should examine the requirements of the cited export
provision or provisions carefully to determine whether you can export a particular product in
compliance with those requirements.
Type of
Product
Status Under the
Federal Food,
Drug, and
Cosmetic Act or
the Public Health
Service Act
(PHSA)
Intended for
Commercial
Distribution or
Investigational
Use
Approved/
Legally
Marketed
in a Listed
Country
Possible Export
Provision Options
and Relevant
Guidance
Document
Chapter
Section
801(e)(1)
applies?
Sections
802(f)
and
802(g)
apply?
Special
Requirements
n/a 	801(f)
See part VI
Yes 	No 	–	Drug
(including
Biological
Products)
Approved as
distributed in the
U.S., but to be
exported with
different or
additional labeling
requirements or
conditions for use
Commercial
Yes 	802(b)(1)
See part VII C and
D
Yes 	Yes 	–
Drug
(including
Biological
Products)
Requires approval
under section 505
of the Act or
licensing under
section 351 of the
PHSA, and does
not have OR not
in compliance with
approval –
includes drugs not
in compliance with
OTC monographs
– or licensing
Commercial 	Yes 	802(b)(1)
See part VII C and
D
Yes 	Yes 	–
Yes 	802(b)(1)
See part VII C and
D
Yes 	Yes 	-	Drug
(including
Biological
Products)
Requires approval
under section 505
of the Act or
licensing under
section 351 of the
PHSA, and does
not have OR not
in compliance with
approval –
includes drugs not
in compliance with
OTC monographs
– or licensing
Investigational
n/a 	802(c)
See part VIII
Yes 	Yes,
except
for notifi-
cation
under (g)
-
6

Type of
Product
Status Under the
Federal Food,
Drug, and
Cosmetic Act or
the Public Health
Service Act
(PHSA)
Intended for
Commercial
Distribution or
Investigational
Use
Approved/
Legally
Marketed
in a Listed
Country
Possible Export
Provision Options
and Relevant
Guidance
Document
Chapter
Section
801(e)(1)
applies?
Sections
802(f)
and
802(g)
apply?
Special
Requirements
Drug
(including
Biological
Products)
Requires approval
under section 505
of the Act or
licensing under
section 351 of the
PHSA, and does
not have OR not
in compliance with
approval -
includes drugs not
in compliance with
OTC monographs
- or licensing
Investigational 	n/a 	21 CFR 312.110 	- 	- 	See provisions
of 312.110 for
specific
options and
requirements
Drug
(including
Biological
Products)
Requires approval
under section 505
of the Act or
licensing under
section 351 of the
PHSA, and does
not have OR not
in compliance with
approval –
includes drugs not
in compliance with
OTC monographs
– or licensing
Commercial,
but exported to
a listed country
for further
formulation,
processing, etc.
No, but
exported
in anticipa-
tion of
market
authoriza-
tion
802(d)
See part IX
Yes 	Yes,
except
for notifi-
cation
under (g)
–
Drug
(including
Biological
Products)
Requires approval
under section 505
of the Act or
licensing under
section 351 of the
PHSA, and does
not have OR not
in compliance with
approval –
includes drugs not
in compliance with
OTC
monographs– or
licensing
Commercial;
exported to an
unlisted country
No. 	802(b)(2) or
802(b)(3)
See part VII F
Yes 	Yes,
except
for notify-
cation
under (g)
Both require a
submission to
FDA and a
determination
by FDA before
the export can
begin
Drug
(including
Biological
Products)
Requires approval
under section 505
of the Act or
licensing under
section 351 of the
PHSA, and does
not have OR not
in compliance with
approval –
includes drugs not
in compliance with
OTC monographs
– or licensing
Intended for
use in a tropical
disease or other
disease not of
significant
prevalence in
the U.S.
No 	802(e) is an option
for an export to an
unlisted country if
the product does
not qualify for
export under any
other provision of
section 802 of the
Act
See part X
Yes 	Yes,
except
for notifi-
cation
under (g)
Requires
approval of an
application to
FDA before
the export can
begin
7

Type of
Product
Status Under the
Federal Food,
Drug, and
Cosmetic Act or
the Public Health
Service Act
(PHSA)
Intended for
Commercial
Distribution or
Investigational
Use
Approved/
Legally
Marketed
in a Listed
Country
Possible Export
Provision Options
and Relevant
Guidance
Document
Chapter
Section
801(e)(1)
applies?
Sections
802(f)
and
802(g)
apply?
Special
Requirements
Drug
(including
Biological
Product)
Adulterated or
Misbranded BUT
does not require
approval under
section 505 of the
Act or licensing
under section 351
of the PHSA
Commercial 	n/a 	801(e)(1)
See part V A and
B
Yes 	No 	–
Insulin or
Antibiotic
Drug
Adulterated or
Misbranded
(irrespective of
status under
section 505 of the
Act or section 351
of the PHSA
Commercial 	n/a 	802(i) and
801(e)(1)
See part V A and
B
Yes 	No 	–
Biological
Product
Partially
processed
biological product
under section 351
of the PHSA
To be exported
for further
manufacture
outside the U.S.
n/a 	section 351(h) of
the PHSA
See part V A, B,
and E
Yes 	No 	–
Device 	Adulterated or
Misbranded BUT
complies with any
applicable
requirement of
sections 514 and
515 of the Act, is
not exempt from
sections 514 or
515 of the Act by
section 520(g) of
the Act, and is not
a banned device
under section 516
of the Act
Either 	n/a 	801(e)(1)
See part V A, B,
and D
Yes 	No 	–
Device 	Does not comply
with an applicable
requirement of
sections 514 or
515 of the Act, is
exempt from
section 514 or 515
of the Act by
section 520(g) of
the Act, or is a
banned device
under section 516
of the Act
Commercial 	Yes 	802(b)(1)
See part VII C and
D
Yes 	Yes 	–
8

Type of
Product
Status Under the
Federal Food,
Drug, and
Cosmetic Act or
the Public Health
Service Act
(PHSA)
Intended for
Commercial
Distribution or
Investigational
Use
Approved/
Legally
Marketed
in a Listed
Country
Possible Export
Provision Options
and Relevant
Guidance
Document
Chapter
Section
801(e)(1)
applies?
Sections
802(f)
and
802(g)
apply?
Special
Requirements
n/a 	802(c)
See part VIII C
Yes 	Yes,
except
for notifi-
cation
under (g)
A party may
instead
conduct the
export and
investigation
pursuant to
the
requirements
of 21 CFR
Part 812
Device 	Does not comply
with an applicable
requirement of
sections 514 or
515 of the Act, is
exempt from
section 514 or 515
of the Act by
section 520(g) of
the Act, or is a
banned device
under section 516
of the Act
Investigational
Yes 	802(b)(1)
See parts VII C
and D, VIII C
Yes 	Yes
Device 	Does not comply
with an applicable
requirement of
sections 514 or
515 of the Act, is
exempt from
section 514 or 515
of the Act by
section 520(g) of
the Act, or is a
banned device
under section 516
of the Act
Commercial,
but exported to
a listed country
for further
formulation, or
processing, etc.
No, but
exported
in anticipa-
tion of
market
authoriza-
tion
802(d)
See part IX
Yes 	Yes,
except
for notifi-
cation
under (g)
–
Device 	Does not comply
with an applicable
requirement of
sections 514 or
515 of the Act, is
exempt from
section 514 or 515
of the Act by
section 520(g) of
the Act, or is a
banned device
under section 516
of the Act
Either 	n/a 	801(e)(2)
See part V D
Yes 	No 	Must submit
request to
FDA
Device 	Does not comply
with an applicable
requirements of
sections 514 or
515 of the Act, is
exempt from
section 514 or 515
of the Act by
section 520(g) of
the Act, or is a
banned device
under section 516
of the Act
Intended for
use in a tropical
disease or other
disease not of
significant
prevalence in
the U.S.
No 	802(e) is an option
for an export to an
unlisted country if
the product does
not qualify for
export under any
other provision in
section 802 of the
Act
See part X
Yes 	Yes,
except
for notifi-
cation
under (g)
Requires
approval of an
application to
FDA before
the export can
begin
9

Type of
Product
Status Under the
Federal Food,
Drug, and
Cosmetic Act or
the Public Health
Service Act
(PHSA)
Intended for
Commercial
Distribution or
Investigational
Use
Approved/
Legally
Marketed
in a Listed
Country
Possible Export
Provision Options
and Relevant
Guidance
Document
Chapter
Section
801(e)(1)
applies?
Sections
802(f)
and
802(g)
apply?
Special
Requirements
Animal
Drug or
Feed
Adulterated or
Misbranded
Either 	n/a 	801(e)(1)
See part V A and
B
Yes 	No 	If requires
approval
under section
512 of the Act
and is banned
in the United
States, section
801(e)(3) of
the Act
prohibits
export
Food or
Cosmetic
Adulterated or
Misbranded
n/a 	n/a 	801(e)(1)
See part V A and
B
Yes 	No 	–
Drug,
Device,
Biological
Product,
Animal
Drug or
Feed,
Food,
Cosmetic
In full compliance
with the applicable
Act or PHSA
requirements for
distribution and
sale in the United
States
Commercial 	n/a 	No specific export
requirements
No 	No 	–
IV. 	Statutory Background
Some background information on the statutory requirements that existed before the
enactment of the 1996 Amendments is helpful to understand why the 1996 Amendments were
enacted.
A. Historical Background - Exports of Drugs and Biological Products That May Not be Sold in
the United States
The Act’s export provision originated in 1906 as part of the Federal Food and Drugs Act
(Public Law 59-384). Section 2 of the 1906 Federal Food and Drugs Act stated that:
10

* * * no article shall be deemed misbranded or adulterated within the provisions of
this act when intended for export to any foreign country and prepared or packed
according to the specifications or directions of the foreign purchaser when no
substance is used in the preparation or packing thereof in conflict with the laws of
the foreign country to which said article is intended to be shipped; but if said
article shall be in fact sold or offered for sale for domestic use or consumption,
then this proviso shall not exempt said article from the operation of any of the
other provisions of this act.
This export provision was included, with some modifications, in the Federal Food, Drug,
and Cosmetic Act of 1938 (Public Law 75-717) where it was codified as section 801(d). Section
801(d) of the 1938 Act stated that:
A food, drug, device, or cosmetic intended for export shall not be deemed to be
adulterated or misbranded under this Act if it (1) accords to the specifications of
the foreign purchaser, (2) is not in conflict with the laws of the country to which it
is intended for export, (3) is labeled on the outside of the shipping package that it
is intended for export, and (4) is not sold or offered for sale in domestic commerce
* * *.
The 1938 act also defined the terms, “drug” and “new drug,” and these definitions led to
the conclusion that section 801(d) of the 1938 Act did not apply to new drugs that did not comply
with section 505 of the Act. (See, e.g., United States v. An Article of Drug, etc * * *
Ethionamide-INH, No. 67 C 288 (E.D. N.Y. Aug. 19, 1967); United States v. Yaron Laboratories,
Inc., 365 F.Supp. 917, 919 (N.D. Cal. 1972); Compliance Policy Guide 7132c.01 (Oct. 1, 1980).)
As a result, the Act was interpreted as permitting the export of approved drugs, but not permitting
the export of unapproved new drugs. This interpretation was viewed as imposing hardships on
the pharmaceutical industry (by impairing its ability to compete in international markets) without
any accompanying public health benefits (see S. Rept. 99-225, 99th Cong., 2d sess. 5-6 (1985)).
To remedy the situation, Congress enacted the Drug Export Amendments Act of 1986
(Public Law 99-660). For human drug products and biological products, the 1986 Amendments
created section 802 of the Act and established three separate “tracks” for exporting unapproved
drugs and unlicensed biological products. Under “track 1,” FDA was authorized to approve an
11

application for the export of new human and animal drugs and biological products that were not
approved in the United States, so long as the drug contained the same active ingredient(s) as a
product for which marketing approval in the United States was being sought or the biological
product was one for which licensing was actively being pursued. Exports under “track 1" were
confined to 21 specific countries listed in section 802 of the Act. Those countries were: Australia,
Austria, Belgium, Canada, Denmark, the Federal Republic of Germany, Finland, France, Iceland,
Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Portugal, Spain,
Sweden, Switzerland, and the United Kingdom.
Under “track 2,” FDA was authorized to approve the export of drugs and biological
products intended for the treatment of tropical diseases. Persons seeking to export a drug under
track 2 had to submit an application to FDA, and FDA had to find, based on “credible scientific
evidence,” that the drug would be safe and effective in the country to which it would be exported
in the prevention or treatment of a tropical disease in that country.
“Track 3" applied to partially processed biological products and amended section 351 of
the PHS Act. FDA was authorized to approve the export of partially processed human biological
products intended for further manufacture in any of the 21 listed countries, but the final product
had to be approved or in the process of receiving approval from the foreign country.
Additionally, the 1986 Amendments added a new section 801(d) of the Act (regarding
importation of drugs), and renumbered the existing section 801(d) as a new section 801(e)(1) of
the Act.3
The 1986 Amendments, however, presented several problems and concerns. One
significant problem was that the 1986 Amendments limited exports of most unapproved drugs and
biological products to 21 countries. Although the 1986 Amendments provided criteria for adding
more countries to the list, it omitted any administrative mechanism for doing so. Consequently,
3 The 1986 Amendments did not alter the export requirements for insulin and antibiotics.
These products remained subject to the basic export requirements that are now in section
801(e)(1) of the Act because the products were subject to approval under provisions of the Act
separate from section 505 of the Act and, as a result, exports could occur without prior FDA
approval under section 802 of the Act.
12

exports of unapproved drugs and biological products to countries that were not on the list were
not permitted.
The requirement that the drug contain the same active ingredient as a drug for which
marketing approval in the United States was being “actively pursued” also caused some concern
in the industry. Questions arose concerning the degree to which the active ingredient had to be
the “same” or how “actively” the manufacturer had to be seeking approval.
The requirements in the 1986 Amendments for FDA approval before a product could be
exported generated criticism and debate as well. The 1986 Amendments required a person to file
an application to export a drug at least 90 days before the date on which the applicant proposed to
export the drug, and required FDA to publish a notice in the Federal Register identifying the
applicant, the drug to be exported, and the country to which the drug was being exported (for
Track 1 exports only). The 1986 Amendments also established requirements for the application
as well as the agency's action on an application. For example, if the agency decided to disapprove
an application, it had to provide a written statement to the applicant describing deficiencies that
the applicant must correct and give the applicant 60 days to correct those deficiencies. Some
firms charged that this approval process took too long; others questioned why the United States
should have to approve the export of a product to a foreign country, particularly when the foreign
country had its own public health authorities or had approved the product for marketing.
B. Historical Background - Exports of Animal Drugs That May Not Be Sold in the United States
As stated earlier, section 801(e) of the Act was construed as not applying to the
exportation of unapproved new human drugs. This interpretation also covered unapproved new
animal drugs, and was made explicit in 1968 as part of the Animal Drug Amendments of 1968
(Public Law 90-399). Although the initial Congressional bill would have permitted exportation of
unapproved new animal drugs, Congress, at the request of the then-Department of Health,
Education, and Welfare, elected to amend section 801 of the Act to prevent the exportation of
unapproved new animal drugs and animal feed containing unapproved new animal drugs (see S.
Rept. 1308, 90th Cong., 2d Sess., 1968 U.S. Code Cong. & Admin. News 2160). The legislative
history explained that the amendment’s purpose was to “preserve, essentially, the status quo with
13

respect to the export exemption” (id.).
The Drug Export Amendments Act of 1986 altered the export requirements for
unapproved new animal drugs in the same manner that it changed the export requirements for
unapproved new human drugs (such as limiting exports to 21 specific countries and requiring the
exporter to be pursuing product approval in the United States as a condition for allowing
exportation). Consequently, under the 1986 amendments, an unapproved new animal drug could
be exported under section 802 of the Act.
C. Historical Background - Exports of Devices That May Not Be Sold in the United States
As stated earlier, then-section 801(d) of the Federal Food, Drug, and Cosmetic Act of
1938 (now codified at section 801(e) of the Act) stated that a food, drug, device, or cosmetic
intended for export would not be considered adulterated or misbranded if the product: (1) Met the
foreign purchaser’s specifications; (2) was not in conflict with the laws of the country to which it
was being exported; (3) was labeled on the outside of the shipping package that the product was
intended for export; and (4) was not sold or offered for sale in domestic commerce.
This authority remained unchanged until 1976 when, as part of the Medical Device
Amendments Act of 1976 (Public Law 94-295), Congress amended the provision to state that the
four criteria did not apply to any device that did not comply with an applicable requirement under
sections 514 (performance standards) or 515 (premarket approval) of the Act, to devices that were
exempt from sections 514 or 515 of the Act under section 520(g) of the Act (devices subject to an
IDE), and to banned devices (under section 516 of the Act) unless, in addition to requiring
compliance with section 801(e)(1) of the Act, the agency determined that exportation of the
device would not be contrary to the public health and safety and the device had the approval of
the foreign country that would receive the device. In other words, most unapproved devices could
not be exported unless the agency determined that exportation would not be contrary to the public
health or safety and that the foreign country approved of the device. This provision was, and
remains, codified at section 801(e)(2) of the Act (21 U.S.C. 381(e)(2)).
As in the case of FDA drug export approvals, the statutory requirement that FDA approve
device exports led to criticism from the device industry. The device industry criticized the agency
14

for the amount of time FDA took to determine whether an export request met the statutory
criteria. FDA reduced the time for processing device export requests from an average of 91 days
in 1992 to 10 days in 1995. Despite this significant reduction in processing time, the statute’s
export approval requirements were seen as adversely affecting the ability of U.S. firms to enter or
to compete in foreign markets.
D. Enactment of the FDA Export Reform and Enhancement Act of 1996
The FDA Export Reform and Enhancement Act of 1996 (Public Law 104-134, and
amended by Public Law 104-180) addressed the industries’ chief problems and concerns. For
human drugs and biological products that may not be sold in the United States, the 1996
Amendments:
• 	Amended section 801 of the Act to allow exports of approved drugs (except for insulin
and antibiotics) to countries that have different or additional labeling requirements or
conditions for use. The new provision, at section 801(f) of the Act, requires such drugs to
be labeled in accordance with the requirements and conditions for use in the foreign
country and also to be labeled in accordance with the Act. If the drug’s labeling includes
conditions for use that are not approved in the United States, the labeling must state that
such conditions for use have not been approved under the Act.
• 	Replaced section 802 of the Act in its entirety with a new section 802 of the Act that:
ƒ 	Eliminated the requirement for prior FDA approval of exports of unapproved drugs in
most cases,
ƒ 	Significantly expanded the list of countries to which unapproved products can be
exported without prior FDA approval (and also provided administrative mechanisms
for the Secretary of Health and Human Services (the Secretary) to add countries to the
list and for FDA to permit exports of specific products to unlisted countries),
ƒ 	Authorized exports of unapproved drugs and biological products intended for use in
clinical investigations in any of the listed countries,
ƒ 	Authorized the export of certain unapproved products to a listed country in
anticipation of marketing approval in that country,
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ƒ 	Created a simple notification process for most exported products (as opposed to the
application process required under the 1986 Amendments). Notification is not
required for drugs exported for investigational use in a listed country or drugs exported
to a listed country in anticipation of marketing authorization, and
ƒ 	Authorized FDA to permit the export of unapproved products intended to treat tropical
or other diseases that are “not of significant prevalence in the United States.”
For animal drugs that may not be sold in the United States, the 1996 Amendments:
• 	Restricted the authority to export an unapproved new animal drug to section 801(e)(1) of the
Act. Animal drugs cannot be exported under section 802 of the Act because that section
pertains to biological products, devices, and human drugs.
• 	The only unapproved new animal drugs that cannot be exported under section 801 of the Act
are animal drugs that have been “banned in the United States” (see section 801(e)(3) of the
Act).
For devices that may not be sold in the United States, the 1996 Amendments:
• 	Amended section 801 of the Act to permit exportation of certain devices under section 801(e)
of the Act or under section 802 of the Act;
• 	Replaced section 802 of the Act in its entirety with a new section 802 of the Act that:
ƒ 	Eliminated the requirement for prior FDA approval for exports (for devices approved
in a listed country or destined for clinical investigations in a listed country),
ƒ 	Created administrative mechanisms for the Secretary to add countries to the list and
for FDA to approve exports of specific products to unlisted countries,
ƒ 	Authorized exports of unapproved devices intended for use in clinical investigations in
any of the countries identified in section 802 of the Act,
ƒ 	Authorized the export of unapproved devices to a listed country in anticipation of
marketing approval in that country,
ƒ 	Created a simple notification process for exported devices (as opposed to the
application process under section 801(e)(2) of the Act). Notification is not required
for devices exported for investigational use to a listed country or devices exported to a
listed country in anticipation of marketing authorization in the listed country; and
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ƒ 	Authorized FDA to permit the export of unapproved devices intended to treat tropical
diseases or other diseases that are “not of significant prevalence in the United States.”
This document describes the requirements for drugs (both human and animal), biological
products, and devices under sections 801 and 802 of the Act and section 351(h) of the PHS Act,
as amended by the 1996 Amendments. 	The general requirements under section 801(e)(1) of the
Act also apply to exports of foods, cosmetics, antibiotics, and insulin that do not comply with the
Act's requirements for sale and distribution in the United States. (The Act treats exports of
antibiotics and insulin differently from other human drugs (see part VI of this guidance
document).)
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V. General Requirements for Products Exported
Under Section 801(e)(1) of the Act
A. Summary of Section 801(e)(1) of the Act
Section 801(e)(1) of the Act contains general export requirements for any food, drug,
device, or cosmetic that is adulterated or misbranded under the Act. These requirements also
apply to products exported in accordance with sections 801(e)(2), 801(f), or 802 of the Act or
section 351(h) of the PHS Act.4 Depending on the type of product being exported and the legal
authority supporting the product’s exportation, requirements in addition to those in section
801(e)(1) of the Act may apply. The 1996 Amendments made no changes to section 801(e)(1) of
the Act.
Section 801(e)(1) of the Act states that a food, drug, device, or cosmetic intended for
export shall not be deemed to be adulterated or misbranded if the article:
• 	Accords to the specifications of the foreign purchaser;
• 	Is not in conflict with the laws of the country to which it is intended for export;
• 	Is labeled on the outside of the shipping package that it is intended for export; and
• 	Is not sold or offered for sale in domestic commerce.
As a statutory exemption, this provision is to be construed narrowly. The party seeking to export
the product bears the burden of demonstrating that the criteria of the exemption are met.
B. Determining Compliance with Section 801(e)(1) of the Act
During routine inspections, FDA will evaluate whether a firm has complied with section
801(e)(1) of the Act. Consequently, records are very important for demonstrating compliance
4 Section 802(f)(3) of the Act prohibits exportation of a product under section 802 of the
Act if the requirements in section 801(e)(1)(A) through (e)(1)(D) of the Act are not met. The
requirements in section 801(e)(1) of the Act also apply to partially processed biological products
exported under section 351(h) of the PHS Act.
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with each element of section 801(e)(1) of the Act. FDA’s record keeping requirements that
implement section 801(e)(1) of the Act can be found at 21 CFR § 1.101(b).
1. Meeting a Foreign Purchaser’s Specifications
To demonstrate that the product meets the foreign purchaser’s specifications, the firm
exporting the product must maintain records which contain sufficient information to match the
foreign purchaser’s specifications to a particular export (see 21 CFR § 1.101(b)(1)). This could
include details about the product (e.g., dosage strength, dosage form, purity, quality, operating
parameters, composition, etc.) and any details concerning the product’s manufacture (e.g., type of
sterilization process to be used, compliance with a particular manufacturing standard, etc.) as
requested by the foreign purchaser. For example, if the article is food with a food additive that is
not approved in the United States, this could include records showing that the purchaser requested
that the food contain the particular food additive. A second example would be records showing
that the purchaser specifically requested the inclusion or exclusion of a particular manufacturing
step, where the article is violative under U.S. cGMP's due to the presence or absence of that
manufacturing step. A third example is where the foreign purchaser does not request a particular
manufacturing step but instead requests that the product be manufactured pursuant to a set of
specific manufacturing standards that are inconsistent with, or at least different from, U.S.
cGMP's. In this example, sufficient records could include records showing that the purchaser
requested that the product be manufactured pursuant to this set of manufacturing standards and
that the manufacturing process met the specified standards. A fourth example is where the
foreign purchaser places an order for a product but does not provide any specifications (e.g., that a
particular food additive, manufacturing step, or manufacturing standard be used). In such a case,
the foreign purchaser's order, standing alone, would not be sufficient to satisfy section
801(e)(1)(A) of the Act.
In addition, if the foreign purchaser sought 5,000 bottles of drug X tablets, with each
tablet at a 50 mg. dose, FDA would look for records to show that a particular shipment of drug X
to the foreign purchaser consisted of 5,000 bottles of drug X in a 50 mg. tablet form. As noted in
the preamble to the final rule (66 FR 65429 (December 19, 2001)), records stating only that drug
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X was shipped to the foreign purchaser would not be satisfactory because the records would not
reflect whether the purchaser sought a particular dosage or quantity and would not show whether
the export met that dosage specification or whether the quantity that was exported met the
purchaser’s specification.
FDA does not expect complete specifications to accompany every order of the same
product. For example, if an exporter signs a contract to ship the same item to a foreign purchaser
on a monthly basis, the agency would not expect the exporter to obtain complete specifications
for each monthly shipment. However, FDA would expect the exporter to have specifications that
applied to the initial shipment and records showing that subsequent shipments correspond to the
same initial specifications. The agency’s principal interest is to link records to specific export
shipments to verify that a particular exported product met the foreign purchaser’s specifications.
The level of detail in the specifications may vary between orders, but § 1.101(b)(1) requires
exporters to maintain records that demonstrate that the exported product met the foreign
purchaser’s specifications.
FDA recommends that the firm have an English-language translation of the specifications
document or be prepared to translate the document into English at the time of any FDA
inspection.
2. Not in Conflict with the Laws of the Importing Country
Under 21 CFR § 1.101(b)(2), there are two possible ways for demonstrating that the
product to be exported does not conflict with the laws of the importing country. The regulation
states that records demonstrating that the product does not conflict with the laws of the importing
country may consist of either:
• 	a letter from an appropriate foreign government agency, department, or other
authorized body stating that the product has marketing approval from the foreign
government or does not conflict with that country’s laws, or
• 	a notarized certification by a responsible company official in the United States that
the product does not conflict with the laws of the importing country. If a
certification is used, the certification must be in English and include a statement
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acknowledging that the person making the certification is subject to the provisions
of Title 18, section 1001 of the United States Code.5
On July 22, 2002, FDA stated, in response to a petition for reconsideration, that it will generally
not take enforcement action regarding § 1.101(b)(2) while the agency considers whether any
changes are necessary to the regulatory provision as to how a company can demonstrate that the
product to be exported does not conflict with the laws of the importing country. FDA's July 22,
2002, letter also stated "we reiterate that affected parties must continue to comply with the
statutory requirements for exports under sections 801(e) and 802 of the Act." On June 1, 2004,
FDA published an advance notice of proposed rulemaking seeking comments on this issue (69 FR
30842).
3. Shipping Package Labeling Showing That the Product Is Intended for Export
To demonstrate that the product is labeled on the outside of the shipping package that it is
intended for export, § 1.101(b)(3) requires records that show such labeling or labeling statements.
These records may consist of copies of labels or labeling statements, such as “For export only,”
that are placed on shipping packages or, if the exported product lacks a shipping package or
container, on shipping invoices or other documents accompanying the exported product.
4. Product Is Not Sold or Offered for Sale in the United States
To demonstrate that the product is not sold or offered for sale in the United States, §
1.101(b)(4) indicates that production and shipping records for the exported product and
promotional materials may be sufficient.
For example, in situations where there are multiple batches of the same product, batches
of a product that are intended for export throughout the manufacturing process or produced on
manufacturing lines that are dedicated to export markets may meet the requirement in section
801(e)(1)(D) of the Act. Even in these situations, however, if a firm is selling the same product
5 Under 18 U.S.C. 1001, it is a criminal offense to knowingly and willfully submit false
information to the government.
21

both in the United States and overseas and the product for sale in the United States is adulterated
or misbranded in the same way as the product intended for export, then the agency would consider
the product to be sold or offered for sale in domestic commerce. Another situation is where a firm
does not decide to export a specific product until it has already begun the manufacturing process,
for example to meet an overseas inventory need. This also may meet the section 801(e)(1)(D)
requirement if the decision to export the product is made at a distinct, identifiable, and documented
point in the manufacturing process; the product is not adulterated or misbranded at the point the
decision is made; and the action that causes the product to become adulterated or misbranded, such
as conforming the product to a foreign specification, is taken subsequent to the decision. In each
of these situations, the product intended for export should be clearly identifiable and segregable
from product intended for the U.S. market.
If the product's sale in the United States does not violate the Act, and the same product is
intended for export for the same approved use and is accompanied closely by the FDA-approved
labeling (if FDA labeling approval is required), FDA may consider the product to be sold or
offered for sale in the United States. Nonetheless, under these circumstances, FDA would consider
the product to be in compliance with the Act such that it would not have to meet the criteria of
section 801(e)(1) of the Act to be exported. By stating that the product is “accompanied closely”
by the FDA-approved label (if FDA is required to approve the product’s labeling), FDA does not
expect the FDA-approved label be affixed to each exported product, but the agency does expect
the FDA-approved label to be included in the export shipment. The agency recognizes that no
interest would be served by requiring firms to attach FDA-approved labels to exported products
otherwise in compliance with the Act’s requirements for sale and distribution in the United States
if those labels would have to be removed or altered for the product to be sold in a foreign country.
In contrast, if the product to be exported:
• 	involves a use that is not approved in the United States, or
• 	is labeled solely in a foreign language and that foreign language labeling discusses
uses that have not been approved by FDA,
then the product is “unapproved” and falls within the Act’s export provisions. In these cases, FDA
would not consider the product with the foreign language label to be sold or offered for sale in the
22

United States within the meaning of section 801(e)(1)(D) of the Act unless this version of the
product, with the foreign language label, was sold or offered for sale in the United States.
To summarize, the requirements in section 801(e)(1) of the Act apply to foods, drugs (both
human and animal (except for “banned” animal drugs, which may not be exported)), biological
products, devices, and cosmetics intended for export, whether they are exported under section 801
or section 802 of the Act or section 351(h) of the PHS Act. Furthermore, depending on the type of
product being exported and the legal authority supporting the product’s exportation, additional
requirements may apply.
C. Special Restrictions on Animal Drugs
The 1996 Amendments excluded certain animal drugs from exportation. Section 801(e)(3)
of the Act states that animal drugs that have been “banned in the United States” may not be
exported. Neither the 1996 Amendments nor the legislative history explains what constitutes a
“banned” animal drug.
D. Special Requirements for Certain Devices
Some devices have additional statutory requirements before they can be exported under
section 801(e)(1) of the Act. Under section 801(e)(2) of the Act, if a device:
• 	Does not comply with an applicable requirement under sections 514 (performance
standards) or 515 (premarket approval) of the Act,
• 	is exempt from either such section under section 520(g) of the Act, or
• 	is a banned device under section 516 of the Act,
the device may not be exported unless, in addition to the requirements in section 801(e)(1) of the
Act, FDA has determined that device’s exportation is not contrary to the public health and safety
and has the approval of the country to which it is intended for export, or the device is eligible for
export under section 802 of the Act.
The Act provides that any device introduced into interstate commerce after May 28, 1976,
is automatically considered to be a “class III” device requiring premarket approval under section
515 of the Act. Such devices may not be legally marketed unless and until FDA: (1) Classifies the
23

device into class I or II; (2) grants marketing clearance by issuing an order under section 513(i) of
the Act, in response to a report submitted by the sponsor under section 510(k) of the Act,
determining that the device is substantially equivalent to a predicate device that does not require
premarket approval (hereinafter referred to as 510(k) marketing clearance); or (3) issues an order
under section 515(d)(1)(A) of the Act approving an application for premarket approval.
The Act prohibits exportation of class III devices requiring premarket approval unless the
criteria under section 801(e)(2) of the Act are met (or the device qualifies for export under section
802 of the Act). FDA has exercised its enforcement discretion and, to date, has not taken
enforcement action against a firm who has not complied with the export criteria in section
801(e)(2) of the Act, provided that the firm has reasonably concluded that FDA would have
granted 510(k) marketing clearance if a report under section 510(k) of the Act had been submitted.
FDA intends, on a case by case basis, to continue to consider the exercise of its enforcement
discretion in this manner with respect to the requirements in section 801(e)(2) of the Act. FDA
emphasizes, however, even if a firm reasonably believes that its device would receive a 510(k)
marketing clearance, FDA does not intend to consider the exercise of its enforcement discretion in
this manner with respect to the requirements in section 801(e)(1) of the Act.
To help FDA determine whether exportation of the device is not contrary to the public
health and safety, FDA recommends that firms provide basic safety data for the device. Such data
often consists of a statement certifying that a search of medical databases has not identified any
adverse safety data for similar devices or the materials used in the device, or summaries of any
adverse safety data, including a discussion as to why the adverse effects should not be considered
applicable to the device that is to be exported. Brief summaries of available animal safety studies
conducted with the device and safety data from human clinical studies are also helpful. For in
vitro diagnostic devices, where the device is to be the sole determinate of whether a particular
course of treatment will be initiated for a life-threatening disease, the agency recommends that the
firm provide a statement indicating whether an alternative test will be available to confirm the test
results. FDA ordinarily does not need safety data if the device is the subject of an approved IDE
or is considered to have an approved IDE, and will be marketed or used in the importing country
24

for the same intended use.6
To help FDA determine whether exportation of the device has the approval of the country
to which it is intended for export, FDA recommends that the firm obtain a letter from the foreign
country authorizing the device’s importation. If the firm is exporting the device to a country in the
European Economic Area and the device has received a CE mark, documentation of the CE mark
will ordinarily be sufficient.
Additional information regarding device exports under section 801(e)(2) of the Act can be
found in the guidance document entitled, “Procedures for Obtaining FDA Approval to Export
Unapproved Medical Devices.” (To obtain copies of this guidance, see “For Further Information
Contact” in part XII of this document.)
E. Special Requirements for Partially Processed Biological Products
The 1996 Amendments also changed the export requirements for partially processed
biological products. Under section 351(h) of the PHS Act, a partially processed biological product
may be exported if it is:
• 	“Not in a form applicable to the prevention, treatment, or cure of diseases or injuries of
man,”
• 	not intended for sale in the United States, and
• 	intended for further manufacture into final dosage forms outside the United States.
Exports of such products must comply with section 801(e)(1) of the Act and with cGMP’s or
international manufacturing standards as certified by an international standards organization
recognized by the agency.
1. What Constitutes a Partially Processed Biological Product?
FDA interprets the term “partially processed biological products” as meaning biological
products requiring purification, inactivation, fractionation, or significant chemical modification
6 A device may be considered to have an approved IDE if an institutional review board
determines that the device is a non significant risk device, and provided the device has met the
requirements for non significant risk devices under 21 CFR § 812.2(b).
25

(such as the formation or breakage of covalent bonds and the incorporation of peptides into a
diagnostic test kit) before being used in the formulation of a final product. Thus, a finished bulk
product that could be formulated into a finished dosage form through manufacturing steps other
than purification, inactivation, fractionation, or significant chemical modification would not
constitute a partially processed biological product that could be exported under section 351(h) of
the PHS Act. Certain other products, such as source plasma and source leukocytes, also would not
be partially processed biological products because they are finished products (notwithstanding the
possibility that their intended use may be as a source material for further manufacturing into
another product), and would be subject to licensure if distributed in the United States. Note that
unlicensed biological products that do not qualify for export under section 351(h) of the PHS Act
may qualify for export under section 802 of the Act.
Products that do qualify as partially processed biological products include intermediate
biological products that a firm has partially processed and that would be subject to licensure as
final products after the completion of additional manufacturing steps. FDA encourages persons
who may be uncertain as to whether their products are partially processed biological products to
contact the Center for Biologics Evaluation and Research (see the “For Further Information
Contact” in part XII of this document for the address and phone number).
2. cGMP Requirements
Section 351(h) of the PHS Act also requires partially processed biological products to be
“manufactured, processed, packaged, and held in conformity with current good manufacturing
practice requirements” or meet international manufacturing standards recognized by the agency.
FDA inspects firms to ensure that they are in compliance with cGMP’s.
Section 351(h) of the PHS Act refers to “international manufacturing standards as certified
by an international standards organization” recognized by FDA. As of August, 2006, FDA has not
recognized any such international standards organizations for purposes of section 351(h) of the
PHS Act.
3. Additional Requirements Under Section 351(h) of the PHS Act
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All exports of FDA-regulated products that may not be sold or marketed in the United
States, including partially processed biological products exported under section 351(h) of the PHS
Act, must conform to the standard export requirements of section 801(e)(1) of the Act. Thus, a
product intended for export under section 351(h) of the PHS Act must:
• 	Accord with specifications of the foreign purchaser;
• 	not be in conflict with the laws of the country to which it is intended for export;
• 	be labeled on the outside of the shipping package that it is intended for export; and
• 	not be sold or offered for sale in domestic commerce.
Consistent with section 801(e)(1) of the Act, section 351(h)(2) of the PHS Act further requires that
the product may not be intended for sale in the United States.
Records are important in FDA’s evaluation of compliance with section 351(h) of the PHS
Act, including the requirements section 801(e)(1) of the Act. FDA regulations, at 21 CFR
1.101(c), require persons exporting a partially processed biological product under section 351(h) of
the PHS Act to meet the recordkeeping requirements in § 1.101(b) (discussed in part V.B above)
and to maintain the following records:
• 	Records demonstrating that the product for export qualifies as a partially processed
biological product and not in a form applicable to the prevention, treatment, or cure of
diseases or injuries of man;
• 	Records demonstrating that the partially processed biological product was manufactured in
accordance with cGMP’s;
• 	Records demonstrating the distribution of the exported, partially processed biological
products;
• 	Copies of all labeling that accompanies the exported, partially processed biological
product; and
• 	Other records demonstrating that the product is intended for further manufacture into a
final dosage form outside the United States. This may include a container label with the
statement, “Caution: For Further Manufacturing Use Only” and any package insert.
Additionally, firms that manufacture, prepare, or process partially processed biological
products for export must register with FDA and list their products under section 510 of the Act and
27

21 CFR parts 207, 607, or 807, whichever is applicable.
28

VI. 	Labeling Requirements for Drugs and Biological Products Exported
Under Section 801(e)(1) of the Act - Section 801(f) of the Act
The 1996 Amendments contained a new provision that permits the export of drugs (other
than insulin, antibiotics, animal drugs, or drugs exported under section 802 of the Act)7 that may
be sold in the United States and are being exported to a country that has different or additional
labeling requirements or conditions for use (compared to those on the FDA-approved labeling),
and the foreign country requires the drug to be labeled in accordance with those requirements or
uses. For these drugs, section 801(f) of the Act imposes certain labeling requirements. Under
section 801(f)(1) of the Act, the drug intended for export may be labeled in accordance with the
foreign requirements and conditions for use as long as the drug is also labeled in accordance with
the Act.
If the labeling includes conditions of use that are not approved in the United States, section
801(f)(2) of the Act requires the labeling to state that those uses are not approved under the Act.
The Act defines “labeling” as “all labels and other written, printed, or graphic matter (1) upon any
article or any of its containers or wrappers, or (2) accompanying such article.” Thus, to comply
with section 801(f)(2) of the Act, FDA suggests that a firm place a statement on the labeling
regarding the uses that are not approved in the United States wherever an unapproved use appears.
For example, if an unapproved use is on the immediate label and on the product’s container, a
statement identifying the uses that are not approved in the United States would appear on the
immediate label and on the product’s container.
FDA has received questions regarding whether the statement identifying the uses that are
not approved in the United States should be in the language used in the foreign country. Although
7 Insulin and antibiotics are excluded from section 801(f) of the Act because they
historically have been subject only to the export requirements now seen in section 801(e)(1) of the
Act. In 1997, the Food and Drug Administration Modernization Act (Public Law 105-115)
repealed the separate approval provisions for these products and, as a result, made them subject to
section 505 of the Act. In order to permit insulin and antibiotics to continue to be exported under
section 801(e)(1), the 1997 legislation expressly stated that insulin and antibiotics may be exported
without regard to the requirements in section 802 of the Act so long as they meet the export
requirements in section 801(e)(1) of the Act. See section 802(i) of the Act.
29

section 801(f) of the Act is silent on this point, the agency suggests that the statement be in the
language used in the foreign country (i.e., the language of the foreign use labeling as a whole)
because the statutory requirement is more meaningful if foreign consumers can read the statement.
In some instances, products that may be exported in compliance with the labeling
requirements in section 801(f) of the Act may also qualify for export under section 802(b)(1)(A) of
the Act (discussed in part VII.D of this document). In such cases, a firm may elect to export a
product under either section 801(e) or section 802(b) of the Act so long as the product meets the
statutory requirements for export. A drug exported under section 802 of the Act is not subject to
the labeling requirements in section 801(f) of the Act.
30

VII. 	Exports of Unapproved Drugs, Biological Products, and Devices
Under Section 802(b) of the Act
A. Drugs and Biological Products
As stated earlier, courts and FDA have interpreted section 801(e) of the Act as being
inapplicable to unapproved new drugs and biological products. As a result, the 1986 Amendments
amended the Act so that the export of unapproved new drugs and biological products was
regulated under section 802 of the Act.
The 1996 Amendments, insofar as human drugs and biological products are concerned,
modified the scope of section 802 of the Act to state that the provision applies to drugs and
biological products that:
• 	Require approval under section 505 of the Act or, for biological products, require licensing
under section 351 of the PHS Act;
• 	do not have such approval or license; and
• 	are not exempt from section 505 of the Act or section 351 of the PHS Act.
Thus, section 802 of the Act applies to unapproved new human drugs and biological
products and to approved human drugs and biological products being exported for unapproved
uses.8 This includes a drug required to have approval under section 505 of the Act and lacking
such approval, a drug that does not comply with its conditions of approval, and a drug that does
not comply with an applicable over-the-counter drug monograph. If FDA disapproves an
application for a drug or biological product, and that product has been or will be exported to one or
more foreign countries, section 802(a) of the Act requires FDA to notify the appropriate foreign
public health official in those countries of its decision.
Section 802 of the Act also contains special provisions for drugs and biological products
intended for investigational use in a listed country, drugs and biological products intended for
8 Insulin and antibiotics may be exported without regard to the requirements of section 802
of the Act if they meet the requirements in section 801(e)(1) of the Act. See section 802(i) of the
Act and footnote 7, above.
31

further processing or labeling to fill the pipeline in anticipation of marketing authorization in a
listed country, and drugs and biological products intended to treat a tropical disease or disease that
is “not of significant prevalence in the United States.” These provisions are discussed in parts VIII
through X of this document.
B. Devices
Section 802(b) of the Act, like section 801(e)(2) of the Act, applies to devices that:
• 	Do not comply with an applicable requirement under section 514 or 515 of the Act;
• 	are subject to an IDE; or
• 	are banned devices.
This means that devices that have premarket approval are not subject to section 802 of the Act, nor
are devices that are the subject of a marketing clearance under the premarket notification provision
under section 510(k) of the Act. As is the case for disapproved drugs and biological products, if
FDA disapproves an application for premarket approval under section 515 of the Act, and the
device has been or will be exported to one or more foreign countries, section 802(a) of the Act
requires FDA to notify the appropriate foreign public health official in those countries of its
decision.
Section 802’s provisions for products intended for investigational use in a listed country,
intended for further processing or labeling to fill the pipeline in anticipation of marketing
authorization in a listed country, or intended to treat a tropical disease or disease that is “not of
significant prevalence in the United States” also apply to devices.
C. Basic Requirements for All Products Exported Under Section 802 of the Act
Section 802(f) of the Act imposes certain basic requirements for all drugs, biological
products, and devices exported under section 802 of the Act. In brief, these requirements are as
follows:
• 	The product must be manufactured, processed, packaged, and held in “substantial
conformity” with cGMP’s or meet international standards as certified by an
international standards organization recognized by FDA. Neither the 1996
32

Amendments nor its legislative history explains what constitutes “substantial
conformity” with cGMP’s, but the legislative history for the Generic Drug
Enforcement Act of 1992 may be instructive. In discussing the terms “substantial
compliance” with cGMP’s and good laboratory practices, the House Committee on
Energy and Commerce suggested that “substantial compliance” could not mean full
compliance with GMPs because FDA “lacks the continuing presence that would be
necessary to conclude that a firm is in full compliance with GMPs and GLPs” (see
H. Rept. 102-272, 102d Cong., 2d sess. 20 (1992)). FDA interprets the term
“substantial conformity” under section 802(f)(1) of the Act in a similar manner.
The term does mean that the firm should have passed its most recent GMP
inspection (or that GMP violations have been rectified, and the firm has credible
systems and personnel in place to prevent a recurrence of the violation(s)). The
agency has not recognized an international standards organization for purposes of
section 802(f) of the Act, but is examining this issue closely.
• 	The product must not consist in whole or in part of any filthy, putrid, or
decomposed substance and must not have been prepared, packed or held under
insanitary conditions where it may have been contaminated with filth or whereby it
may have been rendered injurious to health;
• 	The container for the product must not be composed, in whole or in part, of any
poisonous or deleterious substance which may render the contents injurious to
health;
• 	The product must have the strength, purity, and quality that it purports or is
represented to possess;
• 	For drugs, no substance may be mixed or packed with the drug that would reduce
the drug’s quality or strength or may substitute in whole or in part for another
substance in the drug;
• 	The product must comply with the requirements in section 801(e)(1) of the Act. (A
discussion of the requirements in section 801(e)(1) of the Act appears in part V.B of
this guidance document. FDA regulations, at 21 CFR 1.101(b), describe the records
33

that a person must retain to demonstrate compliance with section 801(e)(1) of the
Act.)
• 	The product cannot be the subject of a notice by FDA or the U.S. Department of
Agriculture determining that the probability of reimportation of the exported
product would present an imminent hazard to the public health and safety of the
United States, such that exportation must be prohibited;
• 	The product cannot present an imminent hazard to the public health of the country
to which it would be exported; and
• 	The product must be labeled in accordance with the requirements and conditions of
use in the listed country (see part VII.D., below) in which it received valid
marketing authorization, if applicable, and the country to which it would be
exported, and must be labeled in the language and units of measurement used in or
designated by the country to which the drug or device would be exported.
Additionally, a product may not be exported if it is not promoted in accordance with
these labeling requirements.
If the above requirements are not met, section 802(f) of the Act states that the drug or
device may not be exported under section 802 of the Act. Furthermore, in determining whether a
drug or device may present an imminent hazard to the public health of the foreign country or is
improperly labeled or promoted, section 802(f) of the Act requires FDA to consult with the
“appropriate public health official in the affected country.”
Exporters are responsible for determining whether export is permitted under the Act and
whether their exports meet the requirements in section 802(f) of the Act. During an inspection,
FDA will evaluate compliance with the relevant export provisions as appropriate. As discussed
below, section 802(g) of the Act requires persons exporting drugs and devices under section
802(b)(1) of the Act to maintain records of such exported products and the countries to which they
were exported and to provide a simple notification to the agency regarding such exports. FDA’s
export notification requirements can be found at 21 CFR 1.101(d).
34

D. Exports of Unapproved New Drugs, Biological Products, and Devices
to a Listed Country - Section 802(b)(1)(A) of the Act
The principal provision authorizing the exportation of unapproved new drugs, biological
products, and devices is section 802(b)(1)(A) of the Act. Section 802(b)(1)(A) of the Act states
that a drug or device “may be exported to any country, if the drug or device complies with the laws
of that country and has valid marketing authorization by the appropriate authority” in Australia,
Canada, Israel, Japan, New Zealand, Switzerland, South Africa, or any member nation in the
European Union or the European Economic Area. As of July, 2007, the EU countries are: Austria,
Belgium, Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany,
Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland,
Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, and the United Kingdom. The EEA
countries are the EU countries, Iceland, Liechtenstein, and Norway. The number of “listed
countries” expands automatically as countries become members of the EU or the EEA.
This means that a firm whose drug or device has received marketing authorization in any of
the countries listed above can export that drug or device to any country in the world, without
submitting an export request to FDA or receiving FDA approval to export the drug or device, as
long as the drug or device meets applicable requirements of the Act, including the laws of the
country to which the product is being exported. This is a change from the 1986 Amendments,
under which firms had to seek prior FDA approval to export under this provision.
FDA interprets the term “valid marketing authorization” as meaning an affirmative
decision by the appropriate public health authority in a foreign country to permit the drug,
biological product, or device to be sold in that country. For example, under this interpretation, if
country D approves a drug for investigational use, the approval would not constitute “valid
marketing authorization” because country D’s decision did not extend to commercial marketing.
Likewise, a decision by country D to permit sales to another country would not represent “valid
marketing authorization” because it does not permit sales within country D.
Some countries, however, have regulatory systems that permit marketing without an
affirmative act or decision by the government. In such cases, FDA may consider a drug, biological
product, or device to have “valid marketing authorization” if the listed country does not object to
35

the product’s marketing in that country. In these cases, FDA recommends that the firm obtain a
document from the relevant authority in the listed country indicating that it does not object to the
product’s marketing.
As for the word “drug,” the drug to be exported under section 802(b)(1)(A) of the Act
should be the same product as the drug that received marketing authorization in the listed foreign
country. Thus, the issue of whether the drug to be exported must be exactly identical to the drug
authorized in the listed country may depend on the conditions surrounding market authorization in
the foreign country. For example, under this interpretation, if country E’s marketing authorization
applies only to a drug product with a specific composition, rather than to drugs that have a
particular active ingredient or general composition, then the drug that is to be exported from the
United States should have the same composition as the drug that received marketing authorization
in country E. If, however, country E approves a drug product and, as a result of that approval,
permits marketing of other drugs using the same active ingredient, then the “drug” that could be
exported under section 802(b)(1)(A) of the Act could be any drug that has the same active
ingredient.
Similarly, the product’s use can be an issue. If the listed country approved the drug for a
specific use, then the exported drug should be indicated for that specific approved use. For
example, under this interpretation, if country E grants market authorization for a drug only to treat
disease X, then a drug exported under section 802(b)(1)(A) of the Act in reliance on country E’s
marketing authorization should be indicated for treatment only of disease X. If, however, the
listed country’s market authorization is not specific to a particular use, then the exported drug can
be for any use, provided that such use remains consistent with the terms of the listed country’s
market authorization.
Similar concepts apply to devices. Devices that are exported under section 802(b)(1)(A) of
the Act should be similar (to the degree that any variation could not affect the safety or
effectiveness of the product) or identical to the devices that receive marketing authorization in a
listed country, depending on the requirements of that listed country. The uses for the exported
device should also be consistent with the requirements of the listed country.
36

E. Expanding the List of Countries in Section 802(b)(1)(A) of the Act
The list of countries in section 802(b)(1)(A) of the Act can expand. The 1996
Amendments contained a mechanism whereby the Secretary may add other countries to the list,
provided that the country meets certain criteria. These criteria include: (1) Statutory or regulatory
requirements which require the review of drugs and devices for safety and effectiveness by a
government entity in that country and which authorizes marketing approval of only those drugs
and devices that trained and qualified experts acting on behalf of the government have determined
to be safe and effective, (2) statutory or regulatory requirements pertaining to cGMPs, (3) statutory
or regulatory requirements for reporting adverse events and for removing unsafe or ineffective
drugs and devices from the market, (4) statutory or regulatory requirements that a product’s
labeling and promotion be in accordance with the product’s approval, and (5) equivalence of the
country’s marketing authorization system with that in the listed countries.
Under section 802(b)(1)(B) of the Act, the authority to add countries to the list rests solely
in the Secretary of Health and Human Services. Thus, FDA has no authority to add countries to
the list.
F. Exports of Unapproved New Drugs and Biological Products to an Unlisted Country -
Section 802(b)(2) and (b)(3) of the Act
If a firm intends to export an unapproved new drug (including a biological product) to a
foreign country not included in section 802(b)(1)(A) of the Act and the drug does not have valid
marketing authorization in a listed country, the firm has two other options for exporting the
product.9
One option is in section 802(b)(2) of the Act. This section permits a firm to export an
unapproved drug directly to an unlisted country if:
• 	The drug complies with the laws of the foreign country and has valid marketing
9 The provisions of sections 802(b)(2) and (b)(3) of the Act do not apply to devices.
Congress omitted devices from these provisions because it found FDA’s practice of permitting,
under section 801(e)(2) of the Act, exports of devices that had approved IDE’s to be an acceptable
alternative.
37

authorization by the “responsible authority” in that country, and
• 	FDA determines that the foreign country has statutory or regulatory requirements:
ƒ 	Which require the review of drugs for safety and effectiveness by a
government entity in that country and which authorize marketing approval
of drugs which trained and experienced experts have determined to be safe
and effective. The experts must be employed by or acting on behalf of the
foreign government entity and base their determination on adequate and
well-controlled investigations (including clinical investigations);
ƒ 	pertaining to cGMP’s;
ƒ 	for reporting adverse events and for removing unsafe or ineffective drugs
from the market; and
ƒ 	which require that the labeling and promotion be in accordance with the
product’s approval.
FDA recommends that firms intending to export drugs under section 802(b)(2) of the Act
provide to the agency documentation showing that the drug complies with the foreign country’s
laws and has valid marketing authorization. (If the country has a regulatory system that allows
marketing without an affirmative decision by the government, FDA recommends that the firm
obtain a document indicating that the authorities in that country do not object to the product’s
marketing.) The agency also suggests that firms provide documentation so FDA can make its
determination on the foreign country’s statutory and/or regulatory requirements. Copies of the
foreign country’s laws and regulations (in English) may be helpful, but are not required; firms may
also provide a description of the foreign country’s laws and regulations with citations that identify
the precise law or regulation. If FDA cannot make the necessary determinations concerning the
foreign country’s statutory and regulatory requirements, the firm cannot export the drug under
section 802(b)(2) of the Act.
Because section 802(b)(2) of the Act requires FDA to evaluate the foreign country’s
statutory and regulatory system, the agency’s determination concerning the foreign country’s
statutory and regulatory requirements may be applicable to subsequent exports if the foreign
country’s statutes or regulations remain unchanged. 	FDA intends to make decisions under section
38

802(b)(2) publicly available, either through a notice in the Federal Register or through some other
means.
The second option is in section 802(b)(3) of the Act. This section permits a firm to petition
the agency to authorize exportation to an unlisted country if the conditions for export under section
802(b)(1) and 802(b)(2) of the Act cannot be met. Under section 802(b)(3) of the Act, FDA shall
allow exportation of the drug if:
• 	The person exporting the drug: (1) Certifies that the drug would not meet the
conditions for approval under the Act or the conditions for approval in a listed
country; and (2) provides “credible scientific evidence” for the product to be
exported that is acceptable to FDA to show that the drug would be safe and
effective under the conditions of use in the country to which it is being exported.
The statute does not specify what constitutes “credible scientific evidence,” but an
adequate and well-controlled study or studies, animal and in vitro pharmacology
and toxicology studies, microbiology studies (for biological products), and
statistical analyses of data should be helpful; and
• 	the appropriate health authority in the foreign country that is to receive the drug: (1)
Requests approval of the drug’s exportation; (2) certifies that the health authority
understands that the drug is not approved under the Act or by any listed country;
and (3) concurs that the scientific evidence provided to FDA is credible scientific
evidence that the drug would be reasonably safe and effective in the foreign
country. Please note that the foreign health authority must “concur” that the
evidence provided to FDA is credible scientific evidence regarding the drug’s safety
and efficacy; this means that the foreign health authority should base its
concurrence on the same evidence presented to FDA. If the foreign health authority
reviewed different evidence or if FDA cannot determine whether the foreign health
authority reviewed or concurred with the same evidence, then the requirement in
section 802(b)(3) of the Act has not been met. Similarly, FDA has received
requests under section 802(b)(3) of the Act where the requesting party states that
the foreign government “does not object” to the product’s importation; the foreign
39

government’s acquiescence to importation does not satisfy section 802(b)(3) of the
Act’s requirement that the foreign government concur that the scientific evidence
provided to FDA is credible scientific evidence of the drug’s safety and
effectiveness. A letter from the relevant foreign government entity addressing each
item in this paragraph will, in most circumstances, be acceptable.
Exports under section 802(b)(3) of the Act, therefore, differ from exports under section 802(b)(2)
of the Act in two important respects: (1) Exports under section 802(b)(3) of the Act involve the
submission of scientific evidence to FDA and to foreign health authorities; and (2) exports under
section 802(b)(3) of the Act are situation-specific (i.e., they pertain to a specific drug intended for
export to a specific country).
Because of these differences, a decision to allow exports of a particular drug under section
802(b)(3) of the Act does not extend to other drugs. Section 802(b)(3) of the Act requires a person
to provide FDA with “credible scientific evidence” that the drug will be safe and effective under
the conditions of use in the foreign country, and the foreign country must concur that the scientific
evidence provided to FDA is credible scientific evidence that the drug would be reasonably safe
and effective. However, because drug products may differ in formulation, dosage, route of
administration, or other respects, scientific evidence to show that one drug is safe and effective
may not necessarily show that another drug, made by a different firm or even the same firm, is safe
and effective. As a result, the Act’s emphasis on providing and reviewing credible scientific
evidence will, in most cases, prevent a person from relying on an earlier decision to allow
exportation under section 802(b)(3) of the Act.
FDA has 60 days to act on a request to export a drug under section 802(b)(3) of the Act.
The agency plans to begin the 60 day period on the date that it receives a complete petition
containing the certification and evidence required by the Act. Please note, however, that while
FDA tries to act on export requests expeditiously, the Act does not allow exportation to proceed if
FDA has not responded within 60 days.
As a reminder, any person who exports a drug under section 802 of the Act also must
comply with the basic export requirements set forth in section 802(f) of the Act and with the
recordkeeping requirements in section 802(g) of the Act.
40

Persons who wish to export a drug under sections 802(b)(2) or 802(b)(3) of the Act should
address any questions to, and send their documentation or requests to:
(For Biological Products)
Division of Case Management (HFM-610),
Center for Biologics Evaluation and Research,
Food and Drug Administration,
1401 Rockville Pike, Suite 200N,
Rockville, 	MD 20852-1448.
(For Drug Products)
Executive Secretariat Team (HFD-6),
Center for Drug Evaluation and Research,
1451 Rockville Pike,
Rockville, 	MD 20852-1420.
41

VIII. Exports of Unapproved Drugs and Devices for Investigational
Use to Listed Countries Under Section 802(c) of the Act
A. Historical Background
The 1986 Amendments did not impose any special requirements for drugs or devices
exported for investigational use. Moreover, FDA did not apply section 801(e) of the Act to
investigational drugs because courts had interpreted section 801 of the Act as not applying to “new
drugs.” As a result, FDA regulated the exportation of unapproved new drugs (including biological
products) for investigational use under its authority over investigational drugs at section 505(i) of
the Act.
FDA issued regulations governing the exportation of unapproved new drugs for
investigational use on January 18, 1984 (49 FR 2095), with minor modifications between 1984 and
2002. These regulations were codified at 21 CFR § 312.110, and so the program became known as
the “312 program.” The regulations required any person who intends to export an unapproved new
drug product for use in a clinical investigation either to have an IND or to submit a written request
to FDA. The regulations required the written request to provide sufficient information about the
drug to satisfy FDA that the drug is appropriate for investigational use in humans, that the drug
will be used for investigational purposes only, and that the drug may be legally used by the
consignee in the importing country for the proposed investigational use. The regulations further
stated that the request must specify the quantity of the drug to be shipped and the frequency of
expected shipments. If FDA authorized exportation of the drug, it would notify the government of
the importing country. The regulations, however, did not apply to drugs approved for export under
section 802 of the Act or section 351(h)(1)(A) of the PHS Act. As discussed in part VIII.B.,
below, the agency recently issued a final rule to modify the regulations for the 312 program.
In contrast, the agency did apply section 801(e) of the Act to investigational devices. This
was partly because, unlike the situation for drugs, the Act contains only one definition for
“device.” The agency issued a regulation on device exports on January 18, 1980 (45 FR 3732 at
3751). The provision, codified at § 812.18(b), simply stated that a person who intends to export an
unapproved device must obtain FDA approval (under what is now part of section 801(e)(2) of the
Act) before exporting the device.
42

B. Impact of the 1996 Amendments on Drugs Exported for Investigational Use
The 1996 Amendments impacted the 312 program significantly by creating a new section
802(c) of the Act. In brief, section 802(c) of the Act permits a firm to export an unapproved drug
for investigational use in any of the listed countries without prior FDA approval or even an IND.
The only requirements are that the drug be exported in accordance with the laws of the foreign
country and comply with the basic export requirements in section 802(f) of the Act. The exporter,
under section 802(g) of the Act, must also maintain records of all drugs exported and the countries
to which they were exported.
It is important to note that section 802(c) of the Act allows exports of drugs and devices
“intended for investigational use in any [listed] country...in accordance with the laws of that
country” (emphasis added). The key statutory phrase is that the drug or device must be intended
for investigational use in a listed country. FDA is aware that some firms have interpreted section
802(c) of the Act as allowing shipments of investigational drugs or devices to an unlisted country
(a practice known as “transshipment”) as long as the shipment passes through a listed country.
FDA disagrees with such an interpretation because the unrestricted transshipment of
investigational drugs and devices from listed to unlisted countries would undermine the express
limitation in section 802(c) of the Act.10 There is no indication that Congress intended to make
listed countries act as mere transfer points for investigational drugs or devices that are destined for
unlisted countries.
Exports under section 802(c) of the Act are subject to the recordkeeping requirement in
section 802(g) of the Act. FDA regulations pertaining to such records can be found at 21 CFR
1.101(e). These exports, however, are not subject to the notification requirements of section
802(g) of the Act.
Additionally, as an alternative to section 802(c) of the Act in some circumstances, section
802(b)(1) of the Act authorizes exportation of an unapproved product, including an investigational
10 In contrast, exports to a listed country, followed by shipment to another listed country is
permitted under section 802(c) of the Act, provided that the shipments are consistent with the laws
of the importing countries, because that provision permits exportation of an investigational drug or
device to any listed country.
43

new drug, to unlisted countries if the drug complies with the foreign country’s laws and has valid
marketing authorization in a listed country. Thus, exports under section 802(b)(1) of the Act may
be made for investigational uses as well as for marketing purposes.
For exports of drugs for investigational use in unlisted countries where the drug product
has not received valid marketing authorization in a listed country, the “312 program” requirements
at § 312.110 remain applicable. On November 23, 2005, FDA issued a final rule to modify the
regulations for the “312 program” (see 70 FR 70720). This final rule describes four mechanisms
for exporting an investigational new drug product:
• 	First, the export may occur if the foreign clinical trial is covered by an IND. This
means that the conduct of the foreign clinical trial will comply with FDA’s IND
requirements.
• 	Second, if the drug has marketing authorization in any country that is listed or
described in section 802(b)(1)(A) of the Act, it may be exported to any country,
including for investigational use. Neither an IND nor prior FDA approval is
necessary. This mechanism corresponds to section 802(b)(1)(A) of the Act, and
exports under this provision are subject to certain statutory requirements. For
example, the export must not conflict with the foreign country’s laws. Federal law
also requires firms to notify FDA when they export products under section
802(b)(1) of the Act.
• 	Third, the export may occur if the drug is to be used in a clinical investigation in
any country that is listed or described in section 802(b)(1)(A) of the Act. Neither
an IND nor prior FDA approval is necessary. This mechanism corresponds to
section 802(c) of the Act, and exports under this provision are subject to certain
statutory requirements. However, federal law does not require firms to notify FDA
when they export drugs under section 802(c) of the Act.
• 	Fourth, the export may occur, without prior FDA approval and without an IND,
upon submission of a certification that the drug and export meet certain conditions
as specified in the rule. This mechanism is the revised “312 program.” In brief, the
would-be exporter must certify to all of the following:
44

ƒ 	The drug is intended for export;
ƒ 	The drug is intended for investigational use in a foreign country;
ƒ 	The drug meets the foreign purchaser=s or consignee=s specifications;
ƒ 	The drug is not in conflict with the foreign country=s laws;
ƒ 	The outer shipping package is labeled to show that the drug is intended for
export from the United States;
ƒ 	The drug is not sold or offered for sale in the United States;
ƒ 	The clinical investigation will be conducted in accordance with § 312.120;
ƒ 	The drug is manufactured, processed, packaged, and held in substantial
conformity with good manufacturing practices;
ƒ 	The drug is not adulterated within the meaning of section 501(a)(1),
(a)(2)(A), (a)(3), (c), or (d) of the Act;
ƒ 	The drug does not present an imminent hazard to public health, either in the
United States, if the drug were to be reimported, or in the foreign country;
and
ƒ 	The drug is labeled in accordance with the foreign country’s laws.
The revised “312 program” also contains special provisions for exportation of an investigational
new drug in the event of a national emergency in a foreign country where the national emergency
necessitates exportation of an investigational new drug. The “national emergency” aspect of the
“312 program” contemplates two different scenarios. In the first, the investigational new drug is to
be stockpiled in the foreign country in anticipation of a national emergency so that the drug may be
available for use if and when the national emergency arises. In the second, the investigational new
drug is needed for use in a sudden and immediate national emergency in a foreign country. FDA
developed the “national emergency” provisions for the “312 program” due to growing concerns
about the possible use of biological, chemical, or other weapons in a terrorist attack and to the
sudden emergence of new diseases. The “national emergency” provisions allow an exporter to
export a drug under the “312 program” without making one or more of the certifications, but it also
requires the Department of Health and Human Services to make certain decisions and, for
45

stockpile situations, requires FDA to approve exportation before exportation occurs.
Since enactment of the 1996 Amendments, most exports of investigational new drugs have
occurred under section 802(c) of the Act or under the 312 program.
C. Impact of the 1996 Amendments on Devices Exported for Investigational Use
The 1996 Amendments also significantly affected investigational device exports. Section
802(c) of the Act permits a firm to export an unapproved device for investigational use in any of
the listed countries, without prior FDA approval or an IDE. As in the case for drugs, the device
must be exported in accordance with the laws of the foreign country, and the exports are subject to
the recordkeeping requirement in section 802(g) of the Act as implemented by 21 CFR 1.101(e).
Yet, unlike the situation for drug exports, the 1996 Amendments permit device firms to
export a device either under section 801(e)(2) of the Act or under section 802 of the Act. The
authority selected is important because each section of the Act carries its own statutory
requirements.
For example, if company F wants to export an unapproved device for investigational use to
a listed country, it could:
• 	Export the device under section 801(e) of the Act. Under this provision, the
exporter would need to comply with section 801(e)(1) of the Act and, depending on
the device, might have to comply with section 801(e)(2) of the Act and submit
information that would enable FDA to determine that exportation is not contrary to
the public health and safety and that the foreign country approves of the
exportation, or
• 	Export the device under section 802(b)(1)(A) of the Act if the device has received
valid marketing authorization in any listed country. Section 802(b)(1)(A) of the Act
permits exportation of an unapproved device, for any purpose, if the device
complies with the laws of the foreign country and has received valid marketing
authorization in a listed country. Exports under section 802(b)(1) of the Act may
also occur to unlisted countries so long as the device complies with the foreign
country’s laws and has valid marketing authorization in a listed country. Exports
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under this option must comply with the basic export requirements at section 802(f)
of the Act (such as being in “substantial conformity” with cGMPs or meeting
international standards as certified by a recognized international standards
organization recognized by the Secretary and complying with section 801(e)(1) of
the Act) and the notification and recordkeeping requirements in section 802(g) of
the Act, or
• 	Export the device to a listed country under section 802(c) of the Act, without prior
FDA approval or the submission of any information to FDA. However, under this
option, compliance with the basic export requirements in section 802(f) of the Act
and the recordkeeping requirement in section 802(g) of the Act and § 1.101(e) is
necessary.
FDA’s regulation at 21 CFR § 812.18 reflects the options for exporting a device for
investigational use, stating that a person exporting an investigational device subject to part 812
must obtain FDA’s prior approval under section 801(e)(2) of the Act or comply with section 802
of the Act.
A firm has the additional option of conducting the investigation under an IDE, in which
case the IDE requirements in part 812 would apply to the export.
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IX. 	Exports of Unapproved Drugs and Devices in Anticipation of
Foreign Approval - Section 802(d) of the Act
Section 802(d) of the Act permits the exportation of an unapproved drug, biological
product, or device “intended for formulation, filling, packaging, labeling, or further processing in
anticipation of market authorization” in any of the listed countries. The only requirements for such
exports are that:
• 	the use of the product must comply with the laws of the foreign country,
• 	the export must comply with the requirements in section 802(f) of the Act, and
• 	records for such exports must be kept in accordance with section 802(g) of the Act.
The range of activities covered under section 802(d) of the Act is very broad, although
mere storage of an unapproved drug, biological product, or device would not constitute
“formulation, filling, packaging, labeling, or further processing.” Additionally, FDA interprets the
phrase “in anticipation of market authorization” as meaning that the firm exporting the product has
filed an application or submission to obtain final marketing authorization in the foreign country.
FDA does not consider an intent to seek market authorization or to file a marketing application at
some future time to constitute “anticipation of market authorization.”
FDA also does not interpret section 802(d) of the Act as allowing anyone to export a drug
as long as someone is seeking market authorization, irrespective of the laws of the foreign country
at issue. 	Section 802(d) of the Act is commonly referred to as allowing firms to “fill the pipeline”
so that a product will be available immediately upon market authorization by a foreign country.
To interpret section 802(d) of the Act as allowing any firm to export the product so long as
someone was seeking market authorization would essentially ignore the word “anticipation” of
market authorization. Arguably, if a firm has not applied for market authorization, it cannot be
“anticipating” market authorization. Thus, the word “anticipation” in section 802(d) of the Act
suggests that the firm exporting the drug, biological product, or device is, in fact, the entity that is
seeking market authorization or would be able to distribute that drug, biological product, or device
legally upon marketing authorization.
Consequently, FDA interprets section 802(d) of the Act as follows. If the foreign country’s
product approval process is specific to an application (i.e., to have marketing authorization, a firm
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must submit an application, and the application must be approved), then a firm seeking to invoke
section 802(d) of the Act to export a drug, biological product, or device to a foreign country must
be seeking market authorization in that foreign country.
If, however, the foreign country’s product approval process would allow multiple products
on the market upon market authorization (i.e., once marketing authorization occurs, any person can
market a drug, biological product, or device that meets the conditions of that marketing
authorization), then a firm seeking to invoke section 802(d) of the Act to export a drug, biological
product, or device to such a foreign country does not have to be the firm that sought marketing
authorization in that foreign country.
This interpretation of section 802(d) of the Act acknowledges both the particular marketing
authorization process in a foreign country and gives appropriate weight to the words “in
anticipation of market authorization.”
Please note that exports in anticipation of market authorization under section 802(d) of the
Act are not subject to the simple notification requirement in section 802(g) of the Act. Instead, the
exporter would send the simple notification to FDA once it receives market authorization and
begins to export the product under section 802(b)(1)(A) of the Act.
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X. Exports of Drugs and Devices for Diagnosing, Preventing, or
Treating a Tropical Disease or a Disease “Not of Significant Prevalence in
the United States” - Section 802(e) of the Act
The 1986 Amendments authorized exports of unapproved new drugs and biological
products intended to prevent or to treat a tropical disease. Under the 1986 Amendments, the
exporter had to submit an export application to FDA. The export application had to:
• 	Describe the drug being exported,
• 	list each country to which the drug would be exported,
• 	contain a certification that the drug would not be exported to a country if the agency
could not find that the drug would be safe and effective in that country,
• 	identify the establishments where the drug is made, and
• 	show that other statutory requirements (such as compliance with cGMP’s) are met.
FDA had to approve the export application before exportation could proceed.
The 1996 Amendments amended the tropical disease provision in several ways. The
provision now covers drugs, including biological products, intended to diagnose, prevent, or treat
tropical diseases; includes devices among the products eligible for exportation; and includes drugs,
biological products, and devices that are intended to treat diseases that are “not of significant
prevalence” in the United States. A disease that is “not of significant prevalence” in the United
States can be one that is not manifested in many Americans (either because the pathogen is not
common or because available treatments have made the disease rare in the United States) or is
indigenous to a particular foreign country or to an area in another country. For example, measles
may be considered to be a disease that is not of significant prevalence in the United States because
most children are immunized against measles. As another example, poliomyelitis would be a
disease that is not of significant prevalence in the United States because a Pan American Health
Organization program eliminated polio in the Western Hemisphere in 1991.
However, like the 1986 Amendments, the 1996 Amendments require FDA to approve an
export application before the product can be exported (see section 802(e) of the Act). The export
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application should contain information showing that the drug or device is intended for use in the
treatment of a tropical disease or a disease that is not of significant prevalence in the United States.
Additionally, the application should contain information that will enable FDA to determine
whether the drug, biological product, or device:
• 	Will not expose patients in the foreign country to an unreasonable risk of illness or
injury, and
• 	will have a probable benefit to health that outweighs the risk of injury or illness
from its use, taking into account the probable risks and benefits of currently
available drug or device treatment, provided that the product is used under
conditions prescribed, recommended, or suggested in the labeling or proposed
labeling. This includes information on the illness to be treated, the drug’s risks, and
the drug’s benefits. By “currently available drug or device treatment,” the applicant
should consider the availability of products that are approved for the particular
disease as well as those that are commonly used to treat the disease, even if the
product is not approved for that indication.
FDA has not received any applications under section 802(e) of the Act. FDA will use a
case-by-case approach on any application received under section 802(e) of the Act until it acquires
sufficient expertise to state general criteria for these applications.
Persons interested in submitting an application under section 802(e) of the Act should
contact the offices listed in part XII of this document.
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XI. Export Notification and Recordkeeping
Under Section 802(g) of the Act
Section 802(g) of the Act requires persons exporting a drug or device under section
802(b)(1) of the Act to provide a “simple notification * * * identifying the drug or device when the
exporter first begins to export such drug or device” to any country listed in section 802(b)(1) of the
Act. If the product is to be exported to an unlisted country, section 802(g) of the Act requires the
exporter to provide a simple notification “identifying the drug or device and the country to which
such drug or device is being exported.”
With respect to all exports pursuant to section 802 of the Act, section 802(g) of the Act
requires the exporter to maintain records of all drugs or devices exported and the countries to
which they were exported.
A. The Content of the Simple Notification
FDA regulations, at 21 CFR 1.101(d), prescribe the content of the simple notification. The
simple notification must contain:
• 	The product’s trade name,
• 	if the product is a drug or biological product, the product’s abbreviated or proper
name or, if the product is a device, the type of device,
• 	if the product is a drug or biological product, a description of the product’s strength
and dosage form or, if the product is a device, the product’s model number, and
• 	if the export is to a country not listed in section 802(b)(1) of the Act, the country
that is to receive the exported article. The notification may, but is not required to,
identify countries listed in section 802(b)(1) of the Act or state that the export is
intended for a listed country without identifying the listed country. FDA
acknowledges that section 802(g) of the Act and § 1.101(d) require exporters to
identify the country that is to receive the exported product only if the country is not
a listed country. However, FDA encourages exporters to identify listed countries
that are to receive the exported product. Identification of the foreign country,
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regardless of whether it is listed or not, will make it easier for FDA to meet its
obligations under sections 802(a) and 802(f)(4), (f)(5), and (f)(6) of the Act which
prohibit exports under certain conditions (such as a finding of an imminent hazard
to the public health) and/or require FDA to consult with the “appropriate public
health official” in the affected country.
If a firm declines to identify a listed country in its simple notification, FDA strongly
recommends that the firm state that it exported the product to a listed country. This will inform
FDA that the omission of a foreign country’s name was not an oversight. If it later becomes
necessary for FDA to contact foreign health officials in a listed country, FDA will inspect the
exporter’s records to determine where the exported products were sent. Inspections consume both
time and resources for FDA and the affected firm, so FDA encourages voluntary disclosure of the
listed countries receiving an exported product.
B. Where to Send the Simple Notification
Notifications should be sent to the following addresses:
For biological products and devices regulated by the Center for Biologics Evaluation and
Research (CBER):
Division of Case Management (HFM-610),
Office 	of Compliance and Biologics Quality,
Center 	for Biologics Evaluation and Research,
Food and Drug Administration,
1401 Rockville Pike, Suite 200N,
Rockville, 	MD 20852-1448.
For human drug products and biological products regulated by the Center for Drug
Evaluation and Research (CDER):
Division of New Drugs and Labeling Compliance (HFD-310),
Center for Drug Evaluation and Research,
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Food and Drug Administration,
11919 Rockville Pike,
Rockville, MD 20852.
For 	devices:
Division of Program Operations (HFZ-305),
Center 	for Devices and Radiological Health,
Food and Drug Administration,
2094 	Gaither Rd.,
Rockville, 	MD 20850.
C. Recordkeeping
As stated earlier, section 802(g) of the Act requires exporters to maintain records of all
drugs and devices exported and the countries to which the products were exported. As provided by
21 CFR 1.101(e), this includes, but is not limited to, records showing:
• 	The product’s trade name,
• 	if the product is a drug or biological product, the product’s abbreviated or proper
name or, if the product is a device, the type of device,
• 	if the product is a drug or biological product, a description of its strength and
dosage form and the product’s lot or control number or, if the product is a device,
the product’s model number,
• 	the consignee’s name and address, and
• 	the date on which the product was exported and the quantity of product exported.
FDA regulations require that these records be kept at the site from which the products were
exported or manufactured, and be maintained for the same period of time as required for records
subject to good manufacturing practice or quality systems regulations applicable to the product.
Under 21 CFR 1.101(e)(2), the records must be made available to FDA, upon request, during an
54

inspection for review and copying by FDA.11
FDA regulations, at 21 CFR 1.101(b), also require records demonstrating compliance with
section 801(e)(1) of the Act. The requirements for records demonstrating compliance with section
801(e)(1) of the Act are different from those required under section 802(g) of the Act. This
guidance document discussed section 801(e)(1) of the Act and records in part V, above. Thus,
because exports under section 802 of the Act must comply with the requirements in section 802(f)
of the Act, and section 802(f) incorporates section 801(e)(1) of the Act, exports under section 802
of the Act must comply with the recordkeeping requirements of both 21 CFR 1.101(b) and
1.101(e).
Additionally, FDA reminds parties that they may need to maintain other records beyond
those specified in section 802(g) of the Act. For example, firms whose products must be in
substantial conformity with cGMP’s under section 802(f)(1) of the Act may be subject to cGMP
recordkeeping requirements under the regulations that apply to their products.
11 On July 22, 2002, FDA stated, in response to a petition for reconsideration, that it would
exercise enforcement discretion and not generally take enforcement action regarding § 1.101(b)
insofar as it pertains to access to records held by food and cosmetic exporters while the agency
considers whether any changes to that provision are necessary. On June 1, 2004, FDA published
an advance notice of proposed rulemaking seeking comments on this issue (69 FR 30842).
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XII. 	For Further Information Contact:
For animal drugs:
Division of Compliance (HFV-230),
Center for Veterinary Medicine,
Food and Drug Administration,
7519 Standish Place
Rockville, 	MD 20855,
240-276-9200
For biological products and devices regulated by CBER:
Division of Case Management (HFM-610),
Office of Compliance and Biologics Quality,
Center for Biologics Evaluation and Research,
Food and Drug Administration,
1401 Rockville Pike, Suite 200N,
Rockville, MD 20852-1448,
301-827-6201.
For devices:
Division of Program Operations (HFZ-305),
Center for Devices and Radiological Health,
Food and Drug Administration,
2094 Gaither Rd.,
Rockville, MD 20850,
240-276-0132
For drugs and biological products regulated by CDER:
Division of New Drugs and Labeling Compliance (HFD-310),
Center for Drug Evaluation and Research,
Food and Drug Administration,
5600 Fishers Lane,
Rockville, MD 20857,
301-827-8930.
For drugs exported for investigational use under § 312.110:
Office of International Programs (HFG-1),
Food and Drug Administration,
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5600 Fishers Lane,
Rockville, MD 20857,
301-443-4480.
For foods and cosmetics:
Division of Enforcement (HFS-605),
Office of Compliance,
Center for Food Safety and Applied Nutrition,
Food and Drug Administration,
5100 Paint Branch Parkway,
College Park, MD 20740
1-888-723-3366
These offices listed above may have additional guidance documents and information on specific
export topics or products.
For general policy questions:
Office of International Programs (HFG-1),
Food and Drug Administration,
5600 Fishers Lane,
Rockville, MD 20857,
301-827-4480 or 404-253-1221
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