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 Purchasers 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 FDAs previous guidance on exports entitled, A Review of FDAs 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 Acts 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 FDAs Compliance Policy Guide 7150.01, 
Certification for Exports , and  FDAs 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. 
  Status Under the      Possible Export       
  Federal Food,  Intended for  Approved/ Provision Options  Section  Sections   Special 
Type of  Drug, and  Commercial  Legally  and Relevant  801(e)(1)  802(f)  Requirements 
Product  Cosmetic Act or  Distribution or  Marketed  Guidance  applies?  and 
the Public Health  Investigational  in a Listed  Document  802(g)  
Service Act  Use  Country  Chapter  apply? 
(PHSA) 
Drug  Approved as  Commercial  n/a  801(f)  Yes  No   
(including  distributed in the   
Biological  U.S., but to be  See part VI 
Products)  exported with  Yes  802(b)(1)  Yes  Yes   
different or   
additional labeling  See part VII C and 
requirements or  D 
conditions for use 
Drug  Requires approval  Commercial  Yes  802(b)(1)  Yes  Yes   
(including  under section 505   
Biological  of the Act or  See part VII C and 
Products)  licensing under  D 
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 
Drug  Requires approval  Investigational  Yes  802(b)(1)  Yes  Yes  - 
(including  under section 505   
Biological  of the Act or  See part VII C and 
Products)  licensing under  D 
section 351 of the  n/a  802(c)  Yes  Yes,  - 
PHSA, and does    except 
not have OR not  See part VIII  for notifi-
in compliance with  cation 
approval   under (g) 
includes drugs not 
in compliance with 
OTC monographs 
  or licensing 
 
6   
  Status Under the      Possible Export       
  Federal Food,  Intended for  Approved/ Provision Options  Section  Sections   Special 
Type of  Drug, and  Commercial  Legally  and Relevant  801(e)(1)  802(f)  Requirements 
Product  Cosmetic Act or  Distribution or  Marketed  Guidance  applies?  and 
the Public Health  Investigational  in a Listed  Document  802(g)  
Service Act  Use  Country  Chapter  apply? 
(PHSA) 
Drug  Requires approval  Investigational  n/a  21 CFR 312.110  -  -  See provisions 
(including  under section 505  of 312.110 for 
Biological  of the Act or  specific 
Products)  licensing under  options and 
section 351 of the  requirements 
PHSA, and does 
not have OR not 
in compliance with 
approval - 
includes drugs not 
in compliance with 
OTC monographs 
- or licensing 
Drug  Requires approval  Commercial,  No, but  802(d)  Yes  Yes,   
(including  under section 505  but exported to  exported    except 
Biological  of the Act or  a listed country  in anticipa- See part IX  for  notifi-
Products)  licensing under  for further  tion of  cation 
section 351 of the  formulation,   market  under (g) 
PHSA, and does  processing, etc.  authoriza-
not have OR not  tion 
in compliance with 
approval  
includes drugs not 
in compliance with 
OTC monographs 
 or licensing 
Drug  Requires approval  Commercial;  No.      802(b)(2) or  Yes  Yes,  Both require a 
(including  under section 505  exported to an    802(b)(3)  except  submission to 
Biological  of the Act or  unlisted country    for notify- FDA and a 
Products)  licensing under  See part VII F  cation  determination 
section 351 of the  under (g)  by FDA before 
PHSA, and does  the export can 
not have OR not  begin 
in compliance with 
approval  
includes drugs not 
in compliance with 
OTC 
monographs or 
licensing 
Drug  Requires approval  Intended for  No   802(e) is an option  Yes  Yes,  Requires 
(including  under section 505  use in a tropical    for an export to an  except  approval of an 
Biological  of the Act or  disease or other  unlisted country if  for notifi- application to 
Products)  licensing under  disease not of  the product does  cation  FDA before 
section 351 of the  significant  not qualify for  under (g)  the export can 
PHSA, and does  prevalence in  export under any  begin 
not have OR not  the U.S.  other provision of 
in compliance with  section 802 of the 
approval   Act 
includes drugs not   
in compliance with  See part X 
OTC monographs 
 or licensing 
 
 
7   
  Status Under the      Possible Export       
  Federal Food,  Intended for  Approved/ Provision Options  Section  Sections   Special 
Type of  Drug, and  Commercial  Legally  and Relevant  801(e)(1)  802(f)  Requirements 
Product  Cosmetic Act or  Distribution or  Marketed  Guidance  applies?  and 
the Public Health  Investigational  in a Listed  Document  802(g)  
Service Act  Use  Country  Chapter  apply? 
(PHSA) 
Drug  Adulterated or  Commercial  n/a  801(e)(1)  Yes  No   
(including  Misbranded BUT   
Biological  does not require  See part V A and 
Product)  approval under  B 
section 505 of the 
Act or licensing 
under section 351 
of the PHSA 
Insulin or  Adulterated or  Commercial  n/a  802(i) and  Yes  No   
Antibiotic  Misbranded  801(e)(1)   
Drug  (irrespective of   
status under  See part V A and 
section 505 of the  B 
Act or section 351 
of the PHSA 
Biological  Partially  To be exported  n/a  section 351(h) of  Yes  No   
Product  processed  for further  the PHSA  
biological product  manufacture   
under section 351  outside the U.S.  See part V A, B, 
of the PHSA   and E 
Device  Adulterated or  Either  n/a  801(e)(1)  Yes  No   
Misbranded BUT   
complies with any  See part V A, B, 
applicable  and D 
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 
Device  Does not comply  Commercial   Yes  802(b)(1)  Yes  Yes   
with an applicable   
requirement of  See part VII C and 
sections 514 or  D 
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  
 
8   
  Status Under the      Possible Export       
  Federal Food,  Intended for  Approved/ Provision Options  Section  Sections   Special 
Type of  Drug, and  Commercial  Legally  and Relevant  801(e)(1)  802(f)  Requirements 
Product  Cosmetic Act or  Distribution or  Marketed  Guidance  applies?  and 
the Public Health  Investigational  in a Listed  Document  802(g)  
Service Act  Use  Country  Chapter  apply? 
(PHSA) 
Device   Does not comply  Investigational  n/a   802(c)  Yes  Yes,  A party may 
with an applicable    except  instead 
requirement of  See part VIII C  for notifi- conduct the 
sections 514 or  cation  export and  
515 of the Act, is  under (g)  investigation 
exempt from  pursuant to 
section 514 or 515  the 
of the Act by  requirements 
section 520(g) of  of 21 CFR 
the Act, or is a  Part 812 
banned device  Yes  802(b)(1)  Yes  Yes   
under section 516     
of the Act   See parts VII C   
and D, VIII C 
 
Device  Does not comply  Commercial,  No, but  802(d)  Yes  Yes,   
with an applicable  but exported to  exported    except 
requirement of  a listed country  in anticipa- See part IX  for notifi-
sections 514 or  for further  tion of  cation 
515 of the Act, is  formulation, or  market  under (g) 
exempt from  processing, etc.  authoriza-
section 514 or 515  tion 
of the Act by 
section 520(g) of 
the Act, or is a 
banned device 
under section 516 
of the Act  
Device   Does not comply  Either   n/a  801(e)(2)  Yes  No  Must submit 
with an applicable    request to 
requirement of  See part V D  FDA 
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  
Device   Does not comply  Intended for  No   802(e) is an option  Yes  Yes,  Requires 
with an  applicable  use in a tropical  for an export to an  except  approval of an 
requirements of  disease or other  unlisted country if  for notifi- application to 
sections 514 or  disease not of  the product does  cation  FDA before 
515 of the Act, is  significant  not qualify for  under (g)  the export can 
exempt from  prevalence in  export under any  begin 
section 514 or 515  the U.S.  other provision in 
of the Act by  section 802 of the 
section 520(g) of  Act 
the Act, or is a   
banned device  See part X 
under section 516 
of the Act  
 
9   
  Status Under the      Possible Export       
  Federal Food,  Intended for  Approved/ Provision Options  Section  Sections   Special 
Type of  Drug, and  Commercial  Legally  and Relevant  801(e)(1)  802(f)  Requirements 
Product  Cosmetic Act or  Distribution or  Marketed  Guidance  applies?  and 
the Public Health  Investigational  in a Listed  Document  802(g)  
Service Act  Use  Country  Chapter  apply? 
(PHSA) 
Animal  Adulterated or  Either  n/a  801(e)(1)  Yes  No  If requires 
Drug or  Misbranded    approval 
Feed  See part V A and  under section 
B  512 of the Act 
and is banned 
in the United 
States, section 
801(e)(3) of 
the Act 
prohibits 
export 
Food or   Adulterated or  n/a  n/a  801(e)(1)  Yes  No   
Cosmetic  Misbranded   
See part V A and 
B 
Drug,  In full compliance  Commercial  n/a  No specific export   No  No   
Device,  with the applicable  requirements  
Biological  Act or PHSA 
Product,  requirements for 
Animal  distribution and 
Drug or  sale in the United 
Feed,  States  
Food, 
Cosmetic 
 
 
 
 
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 Acts 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 amendments 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 purchasers 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 statutes 
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 drugs 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: 
(cid:131)  Eliminated the requirement for prior FDA approval of exports of unapproved drugs in 
most cases,  
(cid:131)  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), 
(cid:131)  Authorized exports of unapproved drugs and biological products intended for use in 
clinical investigations in any of the listed countries,  
(cid:131)  Authorized the export of certain unapproved products to a listed country in 
anticipation of marketing approval in that country, 
 
15   
(cid:131)  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 
(cid:131)  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: 
(cid:131)  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),  
(cid:131)  Created administrative mechanisms for the Secretary to add countries to the list and 
for FDA to approve exports of specific products to unlisted countries, 
(cid:131)  Authorized exports of unapproved devices intended for use in clinical investigations in 
any of the countries identified in section 802 of the Act,  
(cid:131)  Authorized the export of unapproved devices to a listed country in anticipation of 
marketing approval in that country,  
(cid:131)  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 
 
16   
(cid:131)  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).)   
 
17   
 
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 products 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.   
 
18   
with each element of section 801(e)(1) of the Act.  FDAs 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 Purchasers Specifications 
  To demonstrate that the product meets the foreign purchasers specifications, the firm 
exporting the product must maintain records which contain sufficient information to match the 
foreign purchasers 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 products 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 
 
19   
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 
purchasers 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 agencys principal interest is to link records to specific export 
shipments to verify that a particular exported product met the foreign purchasers 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 
purchasers 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 countrys 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 
 
20   
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 products 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 Acts 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 Acts 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 products 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 devices 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 devices 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 cGMPs 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 cGMPs.   
  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  
  26   
  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 FDAs 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 cGMPs; 
  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 products container, a 
statement identifying the uses that are not approved in the United States would appear on the 
immediate label and on the products 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 802s 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 cGMPs 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 cGMPs, but the legislative history for the Generic Drug 
Enforcement Act of 1992 may be instructive.  In discussing the terms substantial 
compliance with cGMPs 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 drugs 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.  FDAs 
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 Ds 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 products 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 
products 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 Es 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 products 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 Es 
marketing authorization should be indicated for treatment only of disease X.  If, however, the 
listed countrys 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 countrys 
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 products 
labeling and promotion be in accordance with the products approval, and (5) equivalence of the 
countrys 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 FDAs practice of permitting, 
under section 801(e)(2) of the Act, exports of devices that had approved IDEs 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: 
(cid:131)  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);  
(cid:131)  pertaining to cGMPs;  
(cid:131)  for reporting adverse events and for removing unsafe or ineffective drugs 
from the market; and 
(cid:131)  which require that the labeling and promotion be in accordance with the 
products 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 countrys 
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 products 
marketing.)  The agency also suggests that firms provide documentation so FDA can make its 
determination on the foreign countrys statutory and/or regulatory requirements.  Copies of the 
foreign countrys laws and regulations (in English) may be helpful, but are not required; firms may 
also provide a description of the foreign countrys laws and regulations with citations that identify 
the precise law or regulation.  If FDA cannot make the necessary determinations concerning the 
foreign countrys 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 countrys 
statutory and regulatory system, the agencys determination concerning the foreign countrys 
statutory and regulatory requirements may be applicable to subsequent exports if the foreign 
countrys 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 drugs 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 drugs 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 products importation; the foreign 
  39   
governments acquiescence to importation does not satisfy section 802(b)(3) of the 
Acts requirement that the foreign government concur that the scientific evidence 
provided to FDA is credible scientific evidence of the drugs 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 Acts 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 countrys 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 FDAs 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 countrys 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   
(cid:131)  The drug is intended for export; 
(cid:131)  The drug is intended for investigational use in a foreign country; 
(cid:131)  The drug meets the foreign purchaser=s or consignee=s specifications; 
(cid:131)  The drug is not in conflict with the foreign country=s laws; 
(cid:131)  The outer shipping package is labeled to show that the drug is intended for 
export from the United States; 
(cid:131)  The drug is not sold or offered for sale in the United States; 
(cid:131)  The clinical investigation will be conducted in accordance with  312.120; 
(cid:131)  The drug is manufactured, processed, packaged, and held in substantial 
conformity with good manufacturing practices; 
(cid:131)  The drug is not adulterated within the meaning of section 501(a)(1), 
(a)(2)(A), (a)(3), (c), or (d) of the Act; 
(cid:131)  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 
(cid:131)  The drug is labeled in accordance with the foreign countrys 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 
countrys laws and has valid marketing authorization in a listed country.  Exports 
  46   
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.   
  FDAs 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 FDAs 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.  
  47   
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 countrys 
product approval process is specific to an application (i.e., to have marketing authorization, a firm 
  48   
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 countrys 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. 
  49   
 
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 cGMPs) 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 
  50   
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 drugs risks, and 
the drugs 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. 
  51   
 
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 products trade name, 
  if the product is a drug or biological product, the products 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 products strength 
and dosage form or, if the product is a device, the products 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, 
  52   
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 countrys 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 
exporters 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,  
  53   
    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 products trade name,  
  if the product is a drug or biological product, the products 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 products lot or control number or, if the product is a device, 
the products model number,  
  the consignees 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 cGMPs 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). 
  55   
 
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, 
  56   
  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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