Importation of Certain FDA-
Approved Human Prescription Drugs, 
Including Biological Products, and 
Combination Products under Section 
801(d)(1)(B) of the Federal Food, 
Drug, and Cosmetic Act 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER)  
Center for Biologics Evaluation and Research (CBER)  
Office of Combination Products (OCP) 
Office of Regulatory Affairs (ORA) 
 
 
September 2020 
Labeling  
Pharmaceutical Quality/CMC  
  
    
Importation of Certain FDA-Approved 
Human Prescription Drugs, Including 
Biological Products, and Combination 
Products under Section 801(d)(1)(B) of 
the Federal Food, Drug, and Cosmetic 
  
Act 
Guidance for Industry 
 
 
Additional copies are available from: 
Office of Communications,  Division of  Drug Information   
Center for Drug Evaluation  and Research 
Food and  Drug Administration  
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002   
Phone: 855-543-3784 or 301-796-3400;  Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov   
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
and/or  
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research  
 Food and Drug  Administration  
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov  
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances      
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER)  
Center for Biologics Evaluation and Research (CBER)  
Office of Combination Products (OCP) 
Office of Regulatory Affairs (ORA) 
 
 
September 2020 
Labeling  
Pharmaceutical Quality/CMC 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS  
 
 
 
I.   INTRODUCTION............................................................................................................. 1  
II.   BACKGROUND ............................................................................................................... 2  
III. DESCRIPTION AND LABELING OF AN MMA PRODUCT ......................................... 3  
A.   Description ...................................................................................................................................... 3  
1.  Drug Products .................................................................................................................................. 3  
2.  Biological Products ......................................................................................................................... 4  
3.  Combination Products ..................................................................................................................... 4  
B.   Labeling .......................................................................................................................................... 5  
IV. SUBMISSION OF A SUPPLEMENT FOR AN MMA PRODUCT .................................. 6  
A.   NDA Supplements .......................................................................................................................... 7  
B.   BLA Supplements .......................................................................................................................... 8  
C.   Requirements and Recommendations Applicable to NDA and BLA Supplements ................. 9  
V. REGISTERING, LISTING, AND PROPOSING AN NDC FOR AN MMA PRODUCT  9  
VI. DEAR HEALTHCARE PROVIDER LETTER ................................................................ 10  
VII. DRUG SUPPLY CHAIN SECURITY ACT ..................................................................... 10  
A. Product Identification ..................................................................................................................... 11  
B.   Product Tracing and Verification ..............................................................................................11  
VIII.  IMPORTATION OF MMA PRODUCTS .................................................................... 11  
A.   Import Entries for MMA Products ............................................................................................ 12  
B.   Manufacturer Authorization for MMA Products ..................................................................... 12  
IX. OTHER REQUIREMENTS APPLICABLE TO AN MMA PRODUCT ....................... 13  
i  Contains Nonbinding Recommendations 
 
Importation of Certain FDA-Approved Human Prescription Drugs, 
Including Biological Products, and Combination Products under 
Section 801(d)(1)(B) of the Federal Food, Drug, and Cosmetic Act:  
Guidance for Industry1  
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
 
I.  INTRODUCTION  
 
This guidance describes recommended procedures to obtain a National Drug Code (NDC) for 
certain FDA-approved prescription drug products that are imported into the United States in 
compliance with section 801 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 
U.S.C. 381).2, 3  As described in further detail in the Background section of this guidance, this 
guidance specifically addresses FDA-approved drugs that are also authorized for sale in a foreign 
country in which the drugs were originally intended to be marketed (hereinafter multi-market 
approved products or MMA products).4    
 
 
1 This  guidance has been  prepared by the Center for Drug Evaluation and Research (CDER), the Center  for 
Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health, the Office  of 
Combination Products in the Office of the Commissioner, and the Office of Regulatory Affairs at the Food and  Drug  
Administration.  
2 For the purposes of this guidance, drug product or  drug will be used to refer to human prescription drug and 
biological  products that are regulated as drugs, except where specific reference is  made to  drugs approved under 
section 505  of the FD&C Act (21 U.S.C. 355) or biological products  licensed under section 351 of  the  Public  Health  
Service Act (PHS Act) (42 U.S.C. 262).  For the purposes of  this guidance,  the terms drug  and drug product  also  
refer to combination products approved under a new  drug  application (NDA)  or biologics license application  (BLA),  
and the term  biological product also refers to combination products approved  under a BLA, except where specific 
reference is made to such combination  products. 
3 This  guidance addresses biological products that are licensed pursuant to approved BLAs under either section 
351(a)  or section 351(k) of the PHS Act, including a biological product that was originally approved in an  NDA that 
was deemed to be a license for the biological product (i.e. an approved 351(a) BLA) pursuant to section 
7002(e)(4)(A) or section 7002(e)(4)(B) of the Biologics Price Competition and  Innovation  Act of 2009.  This 
guidance is not intended to address certain biological products, such as blood and  blood components, including  
those intended  for transfusion, or allogeneic cellular or tissue-based products.  As a general matter, because of 
differences in donor eligibility and infectious disease testing  requirements, we do  not expect that these products, 
when approved for marketing  by a non-U.S. regulatory authority and  originally intended for sale outside the United 
States, would be able to meet the requirements to  obtain a U.S. license. 
4 This term is further defined  for purposes of this guidance in section  III.A.  
  1  Contains Nonbinding Recommendations 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys 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.  
   
II.  BACKGROUND 
 
This guidance is intended to outline a potential pathway by which manufacturers could obtain an 
NDC for an FDA-approved drug that was originally intended to be marketed in a foreign country 
and is also authorized for sale in that foreign country.  Recently, FDA has become aware that 
some drug manufacturers may be interested in offering certain of their drugs at lower costs and 
that obtaining additional NDCs for these drugs may help them to address certain challenges in 
the private market.  By following the procedures  described in this guidance, manufacturers could 
obtain an NDC for an MMA product, which would provide an additional avenue through which 
drugs could be sold at a lower cost in the U.S. market. 
 
Under this pathway, a manufacturer could import such a drug if, consistent with section 
801(d)(1)(B) of the FD&C Act, the drug is manufactured outside the United States and the 
manufacturer5 has authorized the drug to be marketed in the United States and has caused the 
drug to be labeled to be marketed in the United States.6  In addition to other requirements, under 
section 801(a) of the FD&C Act, to be lawfully imported into the United States, drugs must not 
be in violation of section 505 of the FD&C Act (21 U.S.C. 355), or be adulterated in violation of 
section 501 of the FD&C Act (21 U.S.C. 351) or misbranded in violation of section 502 of the 
FD&C Act (21 U.S.C. 352).     
 
This guidance also describes the recommended procedures for submitting certain documentation 
to demonstrate that the drug offered for import, although originally intended for marketing in a 
foreign country, is, in fact, an FDA-approved drug and meets the required specifications in the 
approved new drug application (NDA) or BLA, and thus may be eligible for importation under 
section 801(a) and (d) of the FD&C Act.  In addition, this guidance describes processes for 
registration and listing and obtaining an NDC for such drugs.     
 
This guidance describes recommended labeling changes for MMA products.  In addition, this 
guidance describes the applicable requirements of section 582 of the FD&C Act (21 U.S.C. 
360eee-1), as added by the Drug Supply Chain Security Act (DSCSA) (Title II of Public Law 
113-54).  Finally, this guidance describes importation procedures and other requirements 
applicable to MMA products.7  
 
 
5 For purposes of this  guidance, the manufacturer is the NDA or BLA holder for the MMA  product.  
6 Section 801(d)(1)(B) of the FD&C Act provides that, with limited exceptions:  
[N]o drug that is subject to section  503(b)(1) [of the FD&C  Act] may be imported into the United States 
for commercial use if such  drug is manufactured outside the United States, unless  the manufacturer has 
authorized the  drug to be marketed in the United States and has caused the  drug to be labeled to  be 
marketed in the United States. 
7 The procedures outlined in this guidance are not intended to supplant existing  procedures for temporary  
importation used to mitigate or prevent drug shortages. 
  2  Contains Nonbinding Recommendations 
 
 
III. DESCRIPTION AND LABELING OF AN MMA PRODUCT 
A.   Description  
This guidance specifically addresses the importation of FDA-approved drugs that are also 
authorized for sale in a foreign country in which the drugs were originally intended to be 
marketed, which we are calling MMA products.  For the purposes of this guidance, an MMA 
product is an FDA-approved prescription drug or FDA-licensed biological product, or a 
combination product approved in an NDA or BLA (see 21 CFR Part 3), that:   
   was originally manufactured outside the United States and is authorized for marketing by 
another countrys regulatory authority; 
   is the subject of a supplement to an approved NDA or a BLA, including all the 
information described in section IV.A. or B. of this guidance;  
   is imported into the United States and is authorized by the manufacturer (i.e., the 
applicant) under section 801(d)(1)(B) of the FD&C Act to be marketed in the United 
States;  
   meets the quality standards in the approved application for marketing in the United 
States; 
   continues to meet the quality standards for marketing in its originally intended market;8  
and, 
   differs from the FDA-approved drug or FDA-licensed biological product only with 
regard to the labeling statement described in section III.B of this guidance.    
 
The following sections provide a more specific description of MMA drug products, biological 
products, and combination products, respectively. 
 
1.   Drug Products 
 
For purposes of this guidance, an MMA drug product is a drug product that is the subject of a 
supplement to an FDA-approved NDA in which the applicant demonstrates that the MMA drug 
product is approved by FDA, and, therefore, that the MMA drug product has the FDA-approved 
products: active ingredient(s); active ingredient source(s) (including manufacturing 
facility(ies)), inactive ingredients; dosage form, strength(s), and route(s) of administration; 
container closure systems and other materials used in the production of the FDA-approved drug; 
and meets the specifications of the drug product, as described in the FDA-approved NDA.  An 
MMA drug product would continue to have the same appearance as the FDA-approved product 
before the MMA supplement was approved; for example, an MMA drug product in solid oral 
dosage form would be identical in attributes including size, shape, color, imprint, and scoring.   
 
As described in further detail in section IV of this guidance, an MMA drug product has the same 
formulation, manufacturing process and specifications for the active ingredients and drug 
product as in the chemistry, manufacturing, and controls section of the approved NDA (including 
any information incorporated by reference).  An MMA drug product conforms to the 
 
8 A products failure to meet the quality standards of the regulatory authority in its originally intended market may 
suggest the existence of manufacturing process control issues in the production of that  product.              
  3  Contains Nonbinding Recommendations 
 
specifications described in the approved NDA, including the quality of active ingredients, drug 
products, intermediates, raw materials, reagents, components, in-process materials, container 
closure systems, and other materials used in the production of the drug.  To meet the 
specifications of the application holders existing NDA, an MMA drug product is manufactured, 
packaged, labeled, and tested at the facility(ies) approved in the NDA, including specific 
site(s),production lines, and quality systems.   
 
2.   Biological Products 
 
For purposes of this guidance, an MMA biological product is a biological product that is the 
subject of a supplement to an FDA-approved BLA (including an FDA-approved NDA that was 
deemed to be an FDA-approved BLA) in which the applicant demonstrates that the MMA 
biological product is licensed by FDA, and, therefore, that all lots of the MMA biological 
product have the FDA-licensed products drug substance and drug substance source(s) (including 
manufacturing facility(ies); dosage form, strength, and route(s) of administration; container 
closure systems and other materials used in the production of the FDA-licensed biological 
product; and all lots of the MMA biological product meet the specifications of and comply with 
the FDA-approved BLA.  An MMA biological product would continue to have the same 
appearance as the FDA-licensed product before the MMA supplement was approved; for 
example, an MMA biological product in liquid dosage form would be identical in attributes such 
as color.  
 
As described in further detail in section IV of this guidance, an MMA biological product has the 
same formulation, manufacturing process and specifications for drug substance and biological 
product as in the chemistry, manufacturing, and controls section of the approved BLA (including 
any information incorporated by reference, if appropriate).  An MMA biological product 
conforms to the specifications described in the approved BLA, including the quality of drug 
substances, intermediates, raw materials, reagents, components, in-process materials, container 
closure systems, and other materials used in the production of the biological product.  To meet 
the specifications of the license-holders existing BLA, an MMA biological product is 
manufactured, packaged, labeled, and tested in the facility(ies) and using the manufacturing 
line(s) and quality system(s) used to manufacture the FDA-licensed biological product.  
 
3.   Combination Products 
 
For purposes of this guidance, an MMA combination product is a combination product, as 
defined in 21 CFR 3.2(e), except for any combination product that includes a biological product 
not within the scope of this guidance (see footnote 3).  An MMA combination product is a 
combination product that is the subject of a supplement to an FDA-approved BLA or NDA  and 
for which the product as a whole, including the constituent parts, meets the specifications of the 
FDA approval.9    
 
 
9 If a drug  or  biological product is a constituent part of a cross-labeled combination  product that includes a 
separately distributed device constituent part (see 21 CFR 3.2  (e)(3) and 3.2(e)(4)), the MMA product would be  the 
drug  or  biological product constituent part of the combination product.  The separately  distributed device constituent 
part would not be an MMA  product.  
  4  Contains Nonbinding Recommendations 
 
For purposes of this guidance, an MMA combination product would contain a drug and/or 
biological product constituent part that meets the specifications in the approved application as set 
forth in the applicable paragraphs of section III.A.1. or III.A.2. of this guidance, above.  For 
combination products containing a device constituent part, the device constituent part of an 
MMA combination product is the same device constituent part that is included in the FDA-
approved application for the combination product.  The components, manufacturing materials, 
and specifications of the device constituent part of an MMA combination product are identical to 
those used in the manufacture of the FDA-approved combination product, and the methods used 
in, and the equipment, facilities, and testing and other controls used for, the design, manufacture, 
packaging, labeling, and storage of the combination product, including the device constituent 
part, are the same as those for the FDA-approved combination product.  An MMA combination 
product must comply with current good manufacturing practice requirements set forth in 21 CFR 
Part 4, Subpart A. 
B.   Labeling 
Under the procedures described in this guidance, an MMA product, like any FDA-approved 
prescription drug, must bear the FDA-approved labeling, including the proprietary name (if any) 
and the nonproprietary name,10 the container label, and the carton or package labeling, and be 
accompanied by FDA-approved labeling (e.g., the Prescribing Information) as required under the 
FD&C Act and implementing regulations.  (See, e.g., 21 U.S.C.  352(e), (f); 42 U.S.C.  
262(a)(1)(B)(i); 21 CFR 201.5; 21 CFR 201.57(a)(2); 21 CFR 201.80(a)(1)(i); 21 CFR 
201.100(b), (c); 21 CFR 600.3(k); 21 CFR 610.60; 21 CFR 610.61).    
 
In addition, FDA recommends, as described in the following paragraphs, that the container label 
and carton or package labeling of an MMA product bear features that allow the MMA product to 
be easily distinguishable from non-MMA products and that the container label, carton or package 
labeling, and labeling on or within the package from which the MMA product is dispensed 
(except for FDA-approved patient labeling) include a statement to differentiate the MMA 
product from non-MMA products.   
 
For the container label and carton or package labeling, FDA recommends that the MMA product 
bear a narrow, transparent colored stripe, which we generally recommend to be yellow,11 printed 
horizontally within the top one-half of the container label and carton or package labeling.  The 
shade of color used in the stripe should provide sufficient contrast with the background of the 
container label and carton or package labeling so that the stripe will be easily visible when  
selecting the product from the pharmacy shelf.  Likewise, the stripe should be of a sufficient 
width relative to the size of the container label and carton or package labeling so that the MMA 
product will be easily visible when selecting the product from the pharmacy shelf.      
 
 
10 The nonproprietary  name designated by  FDA in the license for a biological product licensed under the PHS Act is  
its  proper name  (section 351(a)(1)(B)(i) of  the PHS  Act (42 U.S.C. 262(a)(1)(B)(i))  and  600.3(k) (21 CFR  
600.3(k)). 
11 Other colors should be considered in situations where a yellow stripe may not  provide adequate contrast against  
other coloring  used  on a container label or carton  or package labeling, or where a yellow stripe may not allow for 
adequate legibility of the text  on the container label or carton  or package labeling.  
  5  Contains Nonbinding Recommendations 
 
The container label, carton or package labeling, and Prescribing Information should also include 
a statement to help pharmacists distinguish an MMA product.  The container label and carton or 
package labeling should prominently display within the stripe the statement or similar statement, 
Imported following the procedures recommended in FDA Guidance: see [insert current link to 
this guidance on FDA.gov].  In cases where the container label does not have adequate space 
for the statement, the statement should be affixed to the container by other prominent means such 
as a peel-back label.  In the rare event where prominent placement within the stripe is not 
feasible, FDA recommends that this statement appear on the principal display panel of the 
container label and carton or package labeling.  The stripe and statement on the container label 
and carton or package labeling should be sufficiently prominent to help a pharmacist readily 
distinguish the MMA product without obscuring required or recommended information (e.g., 
information that will reduce the risk of medication errors and ensure safe administration of the 
drug).12     
 
FDA recommends that the following statement or similar statement should be included in the 
Prescribing Information: Imported following the procedures recommended in FDA Guidance: 
see [insert current link to this guidance on FDA.gov].  FDA recommends that this statement 
appear in the HOW SUPPLIED/STORAGE AND HANDLING section for products subject to 
21 CFR 201.56(d) and 201.57, or in the HOW SUPPLIED section for products subject to 21 
CFR 201.56(e) and 201.80.  FDA recommends that this statement be associated with the NDC 
number(s) of MMA product(s) (e.g., an asterisk can be placed after each MMA product NDC 
number which will refer to the recommended statement in the HOW SUPPLIED/STORAGE 
AND HANDLING section for products subject to 21 CFR 201.56(d) and 201.57).    
IV. SUBMISSION OF A SUPPLEMENT FOR AN MMA PRODUCT  
This section describes the process by which the holder of an approved application may obtain 
marketing approval of an MMA product and describes the recommended information to be 
submitted with the appropriate supplement for the labeling changes to the approved application.  
An applicant must notify FDA of a change to an approved application in accordance with all 
statutory and regulatory requirements.  FDA recommends that an applicant seeking to market an 
MMA product under an NDA or a BLA submit a supplement, generally a labeling supplement, 
under 21 CFR 314.70 or 601.12(f), respectively.  The labeling statement discussed in this 
guidance would not be appropriately submitted in an annual report under 21 CFR 314.70(d) or 
601.12(f)(3).  FDA also recommends that the cover letter for the supplement note that the 
supplement is an MMA supplement. 
 
FDA recommends that the information supporting the supplement be provided by attestation, as 
described in detail below.  The information contained in the attestation accompanying the NDA 
or a BLA supplement should be known to the applicant.  In addition, the drug or biological 
product should not have left the control of the applicant prior to or during the manufacturing, 
packaging, labeling, and testing processes described in sections A. and B. below to which the 
applicant attests.  
 
12  FDA has issued draft guidance that, when final, will represent FDAs current thinking on this topic.  See FDA 
Draft Guidance for  Industry  Safety Considerations for Container Labels  and Carton  Labeling Design to Minimize 
Medication Errors  (Apr. 2013).  For the most recent version of a guidance,  check the FDA guidance web page at 
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. 
  6  Contains Nonbinding Recommendations 
 
A drug offered for import as an MMA product without an approved supplement may be subject 
to refusal of admission.   
 
In the subsections below, FDA provides recommendations for submission of NDA supplements 
and BLA supplements.  Since there are some differences in the information accompanying the 
submissions for each product type, and for ease in quickly identifying the applicable 
recommendations for the different supplements, the sections are divided by type of application.  
A.   NDA Supplements 
In an NDA supplement seeking to change the FDA-approved labeling for an MMA product, 
FDA recommends that the following information be submitted.  The supplement should include 
information to demonstrate that a product originally intended for sale in another country is the 
FDA-approved product and is manufactured in accordance with the FDA-approved NDA, with 
the exception of the limited labeling differences discussed in this guidance.  The information 
about the MMA product should also establish that the composition of the drug product, as well 
as the entirety of the manufacturing process, from active pharmaceutical ingredient through 
finished product, meets all of the specifications in the chemistry, manufacturing, and controls 
section in the NDA for the FDA-approved drug product (21 CFR 314.50(d)(1)) and any 
submission incorporated by reference (e.g., Type II drug master file).  FDA expects to review the 
addition of the labeling statement discussed in this guidance to ensure it does not distract from, 
interrupt, or distort the required and recommended information in the labeling.   
 
FDA recommends that the supplement include an attestation in the cover letter stating that the 
MMA product has the active ingredient(s), active ingredient source (including manufacturing 
facility(ies)), inactive ingredients, dosage form, strength(s), route(s) of administration, and 
device constituent part(s) (as applicable) described in the NDA.  The application also should 
include information specifying the non-U.S. regulatory authority (Health Canada, the European 
Medicines Agency, etc.) that has authorized the drug product for marketing in a non-U.S. 
jurisdiction.  The attestation should include the applicants commitment that the MMA product 
will continue to meet the quality standards for marketing in its originally intended market.  The 
attestation should establish that the MMA product conforms to the information described in the 
approved application regarding the quality of active ingredients, drug products, intermediates, 
raw materials, reagents, components, in-process materials, container closure systems, and other 
materials used in the production of the drug.  The attestation should establish that the MMA 
product, including the device constituent part (as applicable), is manufactured, packaged, 
labeled, and tested at the facility(ies) approved in the NDA, including specific site(s), production 
lines, and quality system(s).  The attestation described above and executed batch records 
described below would generally be considered an acceptable way to demonstrate in the 
supplement that the MMA product is the FDA-approved product. 
 
The supplement should include the executed batch record, including the certificate of analysis 
(COA), for at least one commercial scale batch of the MMA product produced using each of the 
intended manufacturing line(s).  This analysis should be compared to the analysis completed for 
a recently manufactured commercial batch produced and released for distribution to the U.S. 
market under the approved NDA.    
 
  7  Contains Nonbinding Recommendations 
 
B.   BLA Supplements 
In a BLA supplement seeking to change the labeling for an MMA product, FDA recommends 
that the following information be submitted.13  The supplement should include information to 
demonstrate that a product originally intended for sale in another country is the FDA-licensed 
product and is manufactured in accordance with the FDA-approved BLA, with the exception of 
the limited labeling differences discussed in this guidance.  The information about the MMA 
product should also demonstrate that the lots of the MMA product intended for importation meet 
all of the specifications in the chemistry, manufacturing, and controls section of the approved 
BLA for the biological product.  (See 21 CFR 601.3).  FDA expects to review the labeling 
statement discussed in this guidance to ensure it does not distract from, interrupt, or distort the 
required and recommended information in the labeling.   
 
For licensed biological products, in order to support a demonstration that the MMA product is 
the FDA-licensed biological product, the supplement should include an attestation in the cover 
letter that the MMA product is the FDA-licensed product, including device constituent part(s) (as 
applicable), and is manufactured in accordance with the FDA-approved BLA, with the exception 
of the limited labeling differences discussed in this guidance.  The application should also 
include information specifying the non-U.S. regulatory authority (Health Canada, the European 
Medicines Agency, etc.) that has authorized the biological product for marketing in a non-U.S. 
jurisdiction.  The attestation should include the applicants commitment that the MMA product 
will continue to meet the quality standards for marketing in its originally intended market.  The 
attestation should establish that the MMA product conforms to the information in the FDA-
approved BLA to confirm the quality of drug substances, drug products, intermediates, raw 
materials, reagents, components, in-process materials, container closure systems, and other 
materials used in the production of the biological product.  In the supplement, the applicant 
should include information and data demonstrating that the lots of the MMA product intended 
for importation are, and will continue to be manufactured, packaged, labeled, and tested in the 
FDA-licensed biological products facilities using the same manufacturing line(s) and quality 
system(s) that are used to manufacture the FDA-licensed biological product, including the device 
constituent part (as applicable).  The attestation described above and executed batch records 
described below would generally be considered an acceptable way to demonstrate in the 
supplement that the MMA product is the FDA-licensed product.   
 
The supplement should include an executed batch record, including the COA for a recently 
manufactured commercial batch of the MMA product, and the batch record should contain all 
relevant information regarding the manufacturing process and controls to support the 
demonstration that the batches of the MMA product intended for importation are the FDA-
licensed biological product.  This analysis should be compared to the analysis completed for a 
recently manufactured commercial lot produced and released for distribution to the U.S. market 
under the approved BLA.   
 
 
 
13 Such changes to the approved labeling  of a biological product typically are submitted as prior approval 
supplements (21  CFR 601.12(f)(1)). 
  8  Contains Nonbinding Recommendations 
 
C.   Requirements and Recommendations Applicable to NDA and BLA Supplements 
The applicant should evaluate and address in the supplement the potential impact of shipping 
conditions, including holding and warehousing, necessary to import the MMA product on the 
safety and efficacy, identity, quality, purity, or potency of the MMA product, especially drug 
product stability, and reference supporting data in the NDA or BLA, or provide supporting data 
in the supplement.   
 
The lots of MMA product produced under the approved supplement must meet applicable 
current good manufacturing practice requirements under the FD&C Act and FDA regulations.  
(See 21 U.S.C. 351(a)(2)(B); 21 CFR Parts 210-211; 21 CFR 314.50(d)(1); 21 CFR Parts 600-
680; 21 CFR Part 4).  Current good manufacturing practice records for the lots of the MMA 
product produced under the approved supplement must be established and retained as required 
by FDA regulations.  (21 CFR Part 211, Subpart J; 21 CFR 600.12; 21 CFR Part 4, Subpart A; 
21 CFR Part 820, Subpart M). 
 
V. REGISTERING, LISTING, AND PROPOSING AN NDC FOR AN MMA PRODUCT  
This section describes registration and listing of an MMA product as well as procedures for 
proposing an NDC for the MMA product.  Drug products are identified and reported using a 
unique, three-segment NDC that serves as a unique product identifier for drugs.  The segments of 
the NDC are the labeler code, the product code, and the package code.  Generally, as described 
in further detail below, the request for the NDC is governed by 21 CFR 207.33, 207.35, and 
207.37, and is required to be submitted as part of an electronic submission. 
 
To obtain an NDC for an MMA product, the manufacturer should propose an NDC for the MMA 
product by following the procedures set forth in 21 CFR 207.33.  Although a manufacturer may 
propose a change to either the labeler code or product code, as described above, an MMA 
product differs from the FDA-approved drug or FDA-licensed biological product only with 
regard to the labeling statement.  For this reason, FDA recommends that a manufacturer seeking 
an NDC for an MMA product obtain a new labeler code.  To avoid potential confusion between 
product packages with the same name, the change to the NDC for the MMA product should not 
be solely to the package code.  To avoid confusion, if the MMA product label includes an NDC, 
the MMA product should bear only the NDC that FDA assigns to the MMA product.  FDA 
recommends that the MMA product be listed under the marketing category for multi-market 
approved products, which FDA has added to the registration and listing system.    
 
The procedures for registration and listing and proposing an NDC for MMA products are the 
same as the procedures for all FDA-approved drugs.  Nothing in this guidance changes those 
procedures.  Information about registration and listing, including a webinar, is available at 
www.fda.gov/edrls.  Instructions for registration and listing are available at 
https://www.fda.gov/drugs/drug-registration-and-listing-system-drls-and-edrls/electronic-drug-
registration-and-listing-instructions.  For assistance with registration and listing of an MMA 
product, please email the eDRLS team at edrls@fda.hhs.gov.   
 
 
  9  Contains Nonbinding Recommendations 
 
VI. DEAR HEALTHCARE PROVIDER LETTER 
In addition to the features recommended to be included on MMA product labeling to assist 
pharmacists and other healthcare providers in readily distinguishing an MMA product from other 
FDA-approved drugs, FDA recommends that manufacturers issue a Dear Healthcare Provider 
Letter (DHCP).  DHCP letters are correspondence  often in the form of a mass mailing from the 
manufacturer or distributor of a human drug or from FDA  intended to alert physicians, 
pharmacists, and other health care providers about important new or updated information 
regarding a drug product.  DHCP letters may also be distributed by email and are often made 
available on the Internet (e.g., on company websites or through patient advocacy groups).  FDA 
recommends that a DHCP letter be issued upon approval of a supplement for an MMA product.  
The DHCP letter would help pharmacists and healthcare providers to distinguish an MMA 
product from a counterfeit or unapproved product.  A DHCP letter will also help ensure that 
pharmacists and other healthcare providers can identify products and bill and submit claims 
information in an accurate manner.  FDA has included a suggested template for a DHCP letter as 
Appendix A to this guidance.   
 
VII. DRUG SUPPLY CHAIN SECURITY ACT  
The DSCSA amended the FD&C Act and set forth, among other requirements, product tracing, 
product identifier, verification, and authorized trading partner14 requirements for 
manufacturers,15 repackagers, wholesale distributors, and dispensers to facilitate the tracing of 
certain prescription drugs through the pharmaceutical distribution supply chain.  An MMA 
product offered for import that meets the DSCSA definition of a product, like all DSCSA 
products, is subject to all applicable requirements of section 582 of the FD&C Act (21 U.S.C. 
360eee-1).16  For example, trading partners involved in transactions of DSCSA-covered MMA 
products are required to be authorized, which includes proper registration with FDA or licensure 
at the State or Federal level, as applicable.17  Failure to comply with the requirements of section 
582 of the FD&C Act is a prohibited act under section 301(t) of the FD&C Act (21 U.S.C. 
331(t)) and subject to enforcement action under the FD&C Act. 
 
An MMA product should be imported into the United States by the manufacturer of such product 
or by an authorized trading partner as defined in the DSCSA, when such importation is 
facilitated by the manufacturer under section 801(d)(1)(B) of the FD&C Act.  This will help 
ensure that appropriate product safety and supply chain integrity safeguards are in place to 
reduce the possibility of counterfeit, substandard, or other unapproved products entering the 
closed U.S. supply chain. 
 
 
14  Authorized is defined in section 581(2) of the FD&C Act (21 U.S.C. 360eee(2)). Trading partner is  defined in  
section  581(23)(A)  of the FD&C Act.  Although third-party  logistics providers are also considered trading partners 
under section 581(23)(B) of the FD&C  Act, the requirements of section  582(a)-(e) are not applicable to them. 
15  Manufacturer is  defined  for  the purposes of section 582  of the FD&C Act in  section 581(10) of  the FD&C  Act  
and includes the NDA or BLA holder or co-licensed partner or  affiliate of such holder. 
16  Product is  defined in section 581(13) of the FD&C  Act.  
17 See sections  582(b)(3),  (c)(3), (d)(3), and  (e)(3)  of the FD&C Act. 
 
  10   Contains Nonbinding Recommendations 
 
A. Product Identification 
Under the DSCSA, manufacturers are required to affix or imprint a product identifier to each 
package and homogenous case of a product intended to be introduced in a transaction into 
commerce.18  The manufacturer of a DSCSA-covered MMA product is required to affix or 
imprint the product identifier to each package and homogenous case of a product intended for 
marketing in the United States.19  No transactions in interstate commerce may occur before the 
product identifier is affixed.20  FDA recommends that manufacturers affix or imprint the required 
product identifier to the DSCSA-covered MMA product at the same time at which the FDA-
approved label is applied.  DSCSA-covered MMA products will not be considered 
grandfathered for purposes of the product identifier requirement, because they will be 
packaged after November 27, 2018.21    
B.   Product Tracing and Verification  
Under section 582(b)(1), (c)(1), (d)(1), and (e)(1) of the FD&C Act, trading partners are required 
to provide the subsequent purchaser with product tracing information22 for each transaction23  
involving a DSCSA-covered MMA product.  For example, if the manufacturer transfers 
ownership of a DSCSA-covered MMA product to a wholesale distributor, the wholesale 
distributor generally shall not accept ownership of a product unless the manufacturer has, prior to 
or at the time of the transaction, provided the transaction history, transaction information, and a 
transaction statement for the product.24    
 
Trading partners also are required to have verification systems in place for the DSCSA-covered 
MMA products to comply with the requirements under section 582(b)(4), (c)(4), (d)(4), and 
(e)(4) of the FD&C Act.  These requirements include steps to handle suspect and illegitimate 
product.25   
 
VIII.  IMPORTATION OF MMA PRODUCTS 
This section sets forth recommendations intended to assist importers of MMA products by 
facilitating an efficient and effective admissibility review.  Following the procedures in this 
section will also assist FDA in determining that the importation is authorized and not, for 
example, a counterfeit.   
 
18  See section 582(b)(2) of the FD&C Act.  Product Identifier is defined in section 581(14) and includes the 
products standardized  numerical identifier,  which is composed  of the NDC and a unique alphanumeric serial  
number (see section 581(20)). 
19  See section 582(b)(2) of the FD&C Act. 
20  See section 582(b)(2) of the FD&C Act. 
21 See FDA Guidance for Industry  Grandfathering Policy for Packages and  Homogenous Cases of Product Without  
a Product Identifier (Sept.  2018).  This  guidance and other  guidance documents on the DSCSA are available on  
FDAs website at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
22 For purposes of this  guidance, the term product tracing  information refers to the transaction information,  
transaction history, and transaction statement defined in section 581(26), (25), and (27)  of  the FD&C  Act. 
23  Transaction is defined in section 581(24) of  the FD&C  Act.  
24 See section 582(c)(1)(A) of the FD&C Act. 
25  Suspect product is defined in section 581(21), and illegitimate product is defined in section 581(8), of the FD&C  
Act.  
 
  11   Contains Nonbinding Recommendations 
 
A.   Import Entries for MMA Products 
To help FDA verify that a shipment that purports to contain an MMA product is one in which the 
manufacturer26 has, in fact, authorized the drug to be marketed in the United States and has 
caused the drug to be labeled to be marketed in the United States, we strongly encourage the 
filing of an electronic entry in the Automated Commercial Environment (ACE).  If a 
manufacturer plans to use or authorize another process for making entry of an MMA product 
other than ACE, such as a paper entry, we strongly encourage the manufacturer to inform FDA 
in advance.  FDAs view is that international mail is not appropriate for the importation of MMA 
products.   
   
ACE is currently the sole Electronic Data Interchange (EDI) system authorized by the U.S. 
Customs and Border Protection (CBP) to process electronic entry and entry summary filings for 
FDA-regulated products.  Submitting complete, accurate information in ACE facilitates effective 
and efficient admissibility review by FDA.  FDA regulations set forth the required data elements 
that must be submitted in an electronic entry in ACE, or any other EDI system authorized by 
CBP, for any entry that includes FDA-regulated products (21 CFR Part 1, Subpart D).27    
 
At the time of filing entry in ACE, a filer must submit, among other elements, a Drug Listing 
Number, which is currently the NDC for drugs, including biological products and combination 
products, regulated by CDER (21 CFR 1.74).  For drugs, biological products and combination 
products, regulated by CBER, the Drug Listing Number is not required.  Although not required, 
FDA strongly encourages filers to submit the Drug Listing Number for CBER-regulated MMA 
products in ACE at the time of entry because this information will assist FDAs initial screening 
and further review of the entry, which can significantly increase the likelihood that the entry line 
will receive an automated May Proceed from FDA.   
B.   Manufacturer Authorization for MMA Products  
As stated above, section 801(d)(1)(B) of the FD&C Act provides that, with limited exceptions: 
[N]o drug that is subject to section 503(b)(1) [of the FD&C Act] may be imported 
into the United States for commercial use if such drug is manufactured outside the 
United States, unless the manufacturer has authorized the drug to be marketed in 
the United States and has caused the drug to be labeled to be marketed in the 
United States.   
 
Under this provision, any shipment of a purported MMA product that is offered for importation 
would be subject to refusal unless the manufacturer has authorized the MMA product to be 
marketed in the United States.  It is essential that FDA be provided the information needed to 
confirm that each shipment of a purported MMA product offered for importation has been 
authorized for marketing in the United States by the manufacturer.  To help ensure that a 
particular shipment is authorized, and to help mitigate the potential for counterfeiting, the 
manufacturer should provide information that is sufficient for FDA to verify that each shipment 
 
26 As  noted in  footnote 5, above, for purposes of this guidance, the manufacturer is the NDA or BLA holder for the  
MMA product. 
27 FDA  published its final rule, Submission  of Food  and  Drug  Administration Import Data in the Automated  
Commercial Environment, on  November  29, 2016  (81 FR 85854), and the rule was effective December  29, 2016.  
  12   Contains Nonbinding Recommendations 
 
of an MMA product has, in fact, been authorized by the manufacturer to be marketed in the 
United States.  This information is described in the following paragraph. 
 
FDA strongly encourages manufacturers to submit a report via the Electronic Submissions 
Gateway (ESG) (or to an alternative transmission point identified by FDA) notifying the Agency 
of the importation of an MMA product 10 business days in advance of the first import entry of an 
MMA product covered by the report, which will facilitate FDAs timely admissibility review 
when the MMA product is offered for import.  This report should include: the MMA product 
name, dosage form, and quantity of the MMA product; the name, address, and telephone number 
of the authorized importer; and any temporal or other limitations the manufacturer has placed on 
the authorized importation.  For example, a report could authorize multiple shipments of an 
MMA product for a specified period of time.  An updated report should be timely submitted by 
the manufacturer each time there is a change to the material information in the report; this 
updated report would be submitted before any additional imports affected by the changes are 
entered into ACE.  Manufacturers who choose to submit this report must do so electronically in 
Portable Document Format (PDF) using the Electronic Common Technical Document (eCTD) 
format and the ESG (or to an alternative transmission point identified by FDA).28  The report 
should be referenced and placed in Module 1.  For further information regarding eCTD, please 
refer to FDAs website at 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Electr 
onicSubmissions/ucm153574.htm. 
 
IX. OTHER REQUIREMENTS APPLICABLE TO AN MMA PRODUCT 
An MMA product is subject to all relevant requirements of applicable statutes, including those 
implemented by FDA such as the FD&C Act and the PHS Act; applicable implementing 
regulations under those authorities; and other relevant statutes, including the Social Security Act, 
the Poison Prevention Packaging Act, and the Controlled Substances Act.  The provisions 
implemented by FDA include, but are not limited to, provisions related to adulteration and 
misbranding, and requirements related to adverse event reporting (or postmarketing safety 
reporting for combination products under 21 CFR Part 4, Subpart B), recalls, and Risk 
Evaluation and Mitigation Strategies (REMS).     
 
28 FDA  Guidance for  Industry  Providing  Regulatory Submissions  in Electronic Format   Certain Human 
Pharmaceutical Product Applications and Related Submissions  Using the eCTD Specifications (Jan. 2019).  For the 
most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents.   
  13   Contains Nonbinding Recommendations 
 
Appendix A: Dear Healthcare Provider Letter 
 
Dear Healthcare Provider 
Month Year 
 
IMPORTED PRODUCT FOLLOWING PROCEDURES IN: Importation of Certain FDA-
Approved Human Prescription Drugs, Including Biological Products, and Combination Products 
under Section 801(d)(1)(B) of the Federal Food, Drug, and Cosmetic Act: Guidance for 
Industry - MODEL LETTER 
 
Subject: Importation of TRADENAME (nonproprietary name for drugs/proper name for 
biological products) (NDC #1, NDC #2):  Availability of an FDA-approved prescription  
drug/biological product/combination product that was originally intended to be marketed in a 
foreign country and authorized for sale in that foreign country. 
 
Dear Health Care Provider: 
 
The purpose of this letter is to inform you that TRADENAME (NDC #1, NDC #2), an FDA-
approved prescription drug(s)/biological product(s)/combination product(s) that was/were 
originally intended to be marketed in a foreign country and authorized for sale in that foreign 
country, will be available in the United States.  SPONSOR is marketing TRADENAME (NDC 
#1, NDC #2) in the U.S. following the procedures in FDA guidance issued to describe a means 
for drug companies to offer lower cost versions of their drugs/biological products/combination 
products to Americans.  In addition to marketing TRADENAME with NDC #1 and NDC #2, 
SPONSOR markets other lots of TRADENAME with NDC #10 and NDC #11 in the United 
States.  TRADENAME marketed under NDC #10 and NDC #11 is also an FDA-approved 
prescription drug/biological product/combination product. 
 
TRADENAME (NDC #1, NDC #2) will:  
 
   have FDA-approved container and carton or package labeling;  
   be identical in physical appearance to TRADENAME (NDC #10 , NDC #11), and   
   be accompanied by other FDA-approved labeling (e.g., Prescribing Information, patient 
labeling). This labeling will include the proprietary name (if any) and the  nonproprietary 
name, used for other lots of TRADENAME (NDC #10, NDC #11).   
 
Lots of TRADENAME (NDC #1, NDC #2) will include certain features on the labels and 
labeling to distinguish these lots from other lots of TRADENAME (NDC #10, NDC #11).  These 
features include a yellow (or other contrasting color) stripe printed within the top one-half of the 
container label and carton or package labeling.   
 
The container label (or a peel-back label affixed to the container), the outside carton or package, 
and the Prescribing Information (in the HOW SUPPLIED/STORAGE AND HANDLING 
section or HOW SUPPLIED section) will include the statement (or similar statement),  
Imported following the procedures recommended in FDA Guidance: see [insert current link to 
this guidance on FDA.gov].  This guidance titled, Importation of Certain FDA-Approved 
  14   Contains Nonbinding Recommendations 
 
Human Prescription Drugs, Including Biological Products, and Combination Products under 
Section 801(d)(1)(B) of the Federal Food, Drug, and Cosmetic Act, provides more detailed 
information about this importation pathway, and is available on www.FDA.gov.    
 
Reporting Adverse Events  
 
Heath care providers and patients are encouraged to report adverse events that occur in patients 
taking TRADENAME to SPONSOR at 1-800-xxx-xxxx or to the FDA (Visit 
www.FDA.gov/medwatch, or call 1-800-FDA-1088). 
 
You may also contact our medical information department at 1-800-xxx-xxxx if you have any 
questions about the information contained in this letter or the safe and effective use of 
TRADENAME. 
 
This letter is not intended as a complete description of the benefits and risks related to the use of 
TRADENAME. Please refer to the enclosed prescribing information (and medication guide, if 
there is a medication guide for the product, or any other approved patient information). 
 
Reporting Counterfeit Drugs 
 
If you suspect that you may have a counterfeit drug, please report to FDAs MedWatch office 
(Visit www.FDA.gov/medwatch). 
 
If you are aware of suspicious activity that may be associated with counterfeit prescription drugs, 
please contact FDAs Office of Criminal Investigations (OCI) (Send a report to OCI online at  
https://www.accessdata.fda.gov/scripts/email/oc/oci/contact.cfm or contact OCI headquarters in 
Rockville, Md.: 240-276-9500; Toll Free: 1-800-551-3989).  
 
For additional information, please call Sponsor at 1-800-xxx-xxxx or visit www.tradename.com. 
 
Sincerely, 
 
Company Representative 
 
Enclosure(s): TRADENAME Prescribing Information 
 
  15