Identification of Manufacturing 
Establishments in Applications 
Submitted to CBER and CDER 
Questions and Answers 
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 and Evaluation Research (CBER) 
 
October 2019 
Pharmaceutical Quality/CMC 
 
Revision 1
 
   
Identification of Manufacturing 
Establishments in Applications 
Submitted to CBER and CDER  
Questions and Answers
 
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  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
and/or 
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Center for Biologics Evaluation and Research 
 Food and Drug Administration 
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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 and Evaluation Research (CBER) 
 October 2019 
Pharmaceutical Quality/CMC 
 
 
Revision 1
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  QUESTIONS AND ANSWERS ....................................................................................... 2 
Form FDA 356h Questions/Answers ..................................................................................................... 2 
Module 3 Questions/Answers ................................................................................................................ 6 
General Questions/Answers ................................................................................................................... 8 
  Contains Nonbinding Recommendations 
Identification of Manufacturing Establishments in Applications 
Submitted to CBER and CDER  
Questions and Answers 
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 staff responsible for this guidance as listed on the 
title page.   
 
 
 
I.  INTRODUCTION 
 
This guidance is intended to clarify Agency expectations regarding facility information that 
should be included in original new drug application(s) (NDA); abbreviated new drug 
application(s) (ANDA); original biologics license application(s) (BLA); amendments; 
supplements; chemistry, manufacturing, and controls (CMC) supplements; and resubmissions to 
these submission types.  Submission of Form FDA 356h fulfills the requirement for applicants to 
submit an application form (21 CFR 314.50(a) and 314.94(a)(1); 601.2(a)).  Form FDA 356h 
serves as both a summary of administrative information, as well as a repository of complete 
information on the locations of all manufacturing, packaging, and control sites for both drug 
substance and drug product facilities associated with the application.  This guidance addresses 
questions related to the inclusion and withdrawal of proposed commercial facilities and 
development facilities, the appropriate location within an application for facility information, and 
the type of facility information that should be included in applications.  Applications that include 
appropriate and complete facility information in the establishment information section of Form 
FDA 356h will reduce the frequency of Information Request (IR), Refusal to File (RTF), and 
Refuse to Receive (RTR) actions and increase the efficiency of the application assessment 
process.  This guidance describes the recommended placement of all facility information for both 
original and supplement applications. 
 
This guidance applies to BLA products licensed under section 351 of the Public Health Service 
Act, including In-Vitro Diagnostics regulated as BLAs and drug products marketed (or to be 
marketed) under an NDA or an ANDA under the Federal Food Drug and Cosmetic Act.  This 
guidance applies to all manufacturing locations, including facilities that perform functions under 
contract.  
 
                                                 
1 This guidance was prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research in cooperation with the Center for Biologics and Evaluation Research at the Food and Drug 
Administration.  You may submit comments on this guidance at any time. Submit comments to Docket No. FDA-
2017-D-6821 (available at https://www.regulations.gov/docket?D=FDA-2017-D-6821).  See the instructions in that 
docket for submitting comments on this and other Level 2 guidances. 
  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 
 
The Agency frequently receives questions regarding expectations for inclusion of manufacturing 
establishment information in applications (Module 3) and Form FDA 356h.  In some instances, 
this lack of clarity results in FDA receiving applications that contain extraneous information, 
misplaced information (i.e., not readily accessed by Agency reviewers), or missing information.  
These issues result in delays to the assessment process and in some instances, unnecessary IR, 
RTF, and RTR actions.  This guidance offers detailed recommendations regarding the placement 
of facility information in applications.   
 
III.  QUESTIONS AND ANSWERS  
 
Form FDA 356h Questions/Answers 
 
1.  What facility information should I include in the establishment field on Form FDA 
356h?  
 
For original NDA, ANDA, and BLA applications, amendments, efficacy 
supplements, CMC supplements, and resubmissions to these submission types, the 
applicant should include complete information on the locations of all manufacturing, 
packaging, and control sites for both drug substance and drug product on Form FDA 
356h.  This should include: 
  All drug product (in-process material and final) manufacturing (including 
primary, packaging, and labeling sites) and testing sites, including stability 
testing, that are proposed to be involved in the disposition2 of commercial 
product.  Stability testing information associated with the drug substance and drug 
product should be included in Module 3 (see below).  
  All intermediate (performing operations addressed by the International 
Conference on Harmonisation guidance for industry Q7 Good Manufacturing 
Practice Guidance for Active Pharmaceutical Ingredients (September 2016)) and 
final drug substance manufacturing and testing sites that are proposed to be 
involved in the disposition of commercial product.  This includes sterilization and 
micronization sites. 
                                                 
2 For purposes of this guidance the term disposition is the result of a decision to assign a status within the 
commercial supply chain.  Examples of disposition include lot release, quarantine awaiting further data, or lot 
rejection.  Assays and resulting data, which are used to make disposition decisions, are a part of the commercial 
process control strategy. 
  2  Contains Nonbinding Recommendations 
  For combination products, facilities manufacturing a constituent part of a co-
package or single entity combination product, or drug-device combination product 
that are proposed to be involved in the disposition of commercial product.  This 
includes final kitting facilities and facilities that conduct design control activities, 
including verification and validation, of a device constituent part.  For more 
detailed information on combination products please see guidance for industry 
Current Good Manufacturing Practice Requirements for Combination Products 
(January 2017).3  
  All facilities used for storing or warehousing drug substance, in-process material, 
and commercial drug product under quarantine prior to a disposition decision, 
including any facilities that solely store the stability samples.  
 
2.  Should I list all facilities in Modules 2 and 3 on Form FDA 356h?  
 
No.  Facilities that do not impact or inform the commercial control strategy do not 
need to be listed on Form FDA 356h.  Examples of such facilities can be found below 
in response to Question 1 under Module 3 Questions/Answers. 
 
3.  What facilities should be identified in the establishment field on Form FDA 356h 
when submitting an amendment or a supplement? 
 
Submissions should include complete facility information for existing facilities and 
any changes to previously submitted facility information.  If an applicant is adding a 
new facility or removing a previously submitted facility, this information should be 
captured on Form FDA 356h submitted with the amendment or supplement.  The 
appropriate box should be checked: 
 
Pending:   Introducing a new facility to the application.  
Active:    Already approved for use for that application.   
Inactive:   Approved for use to manufacture the drug under the application, 
but is not currently being utilized.  
Withdrawn:  Any facility withdrawn from the current, pending, original, or 
supplemental submission. 
 
4.  If I have withdrawn a facility, how should I revise Form FDA 356h? 
 
If a facility not previously approved is withdrawn before the application (e.g., original 
or supplement) adding the facility is approved, or if a previously approved facility has 
been withdrawn in a post-approval notification under 21 CFR 314.70 or 601.12, the 
facility should remain on Form FDA 356h with the box withdrawn checked.  For 
amendments, this starts with the first amendment notifying FDA that the facility is 
being withdrawn and all subsequent amendments until the application is either 
                                                 
3 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA 
Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
  3  Contains Nonbinding Recommendations 
withdrawn or approved.  The withdrawn facility should be omitted from the list in 
any subsequent supplement.4 
 
5.  For combination products, should I list the device constituent part manufacturer? 
 
Yes.  For a combination product, any finished device constituent part manufacturing 
facilities that are proposed to be involved in the disposition of commercial products 
should be listed on Form FDA 356h.  This includes facilities that conduct design 
controls activities, including verification and validation, in accordance with 21 CFR 
820.30 for the device constituent part.  In addition, Form FDA 356h should list the 
facilities that manufacture the combination product. 
 
6.  Should I have an FDA Establishment Identifier (FEI) number and Data Universal 
Numbering System (DUNS) number for a given facility?  If so, how do I obtain the 
FEI number and DUNS number or alternatively how can I check to see if a facility 
has already obtained these identification numbers?  
  
Having an FEI number and DUNS number will facilitate the application process and 
establishment registration. 
 
The FEI number is needed by the Agency to proceed with the facility evaluation 
portion of the application assessment.  
 
Section 510 of the Food, Drug, and Cosmetic Act requires that each initial and annual 
drug establishment registration include a Unique Facility Identifier (UFI) (21 U.S.C. 
360(b), (c), and (i)). The Agencys preferred UFI for a drug establishment is the 
DUNS number, assigned and managed by Dun & Bradstreet.5  
 
21 CFR 207.21(a) states that Registrants must register each domestic establishment 
no later than 5 calendar days after beginning to manufacture, repack, relabel, or 
salvage a drug...   
 
21 CFR 207.21(b) states that Registrants must register each foreign establishment 
before a drug ...manufactured, repacked, relabeled, or salvaged at the establishment 
is imported or offered for import into the United States.   
 
FDA recommends that at the time of registration, the owner or operator obtain an FEI 
number.  Although the absence of the FEI number may hinder the timeline for 
assessment of the establishment information contained within your application, you 
should not delay submitting your application due to the absence of an FEI number.  
Rather, you should request an FEI number as soon as possible.     
 
                                                 
4 If further clarification is needed regarding the appropriate action to be taken when a facility is withdrawn, please 
consult with the appropriate FDA review division.    
5 See guidance for industry Specification of the Unique Facility Identifier (UFI) System for Drug Establishment 
Registration (November 2014). 
  4  Contains Nonbinding Recommendations 
To obtain an FEI number for a GDUFA-related facility, email 
FDAGDUFAFEIRequest@fda.hhs.gov. 
 
To obtain an FEI number for a PDUFA- or BsUFA-related facility, email  
PDUFABSUFAFEIRequest@fda.hhs.gov. 
 
Your email should include the following data points: 
(a) Subject:  Foreign or Domestic FEI request for (firm name) 
(b) Company Legal Name for the location for which the activity is being 
conducted  
(c) Company Address for the location for which the activity is being conducted 
(d) Company Point of Contact (name, email, telephone number) 
(e) Activities the firm is going to participate in regarding the drug product 
(manufacturing, labeling, testing, etc.) 
(f) Known drug products (API, finished dose, intermediary) 
(g) Registered with FDA (if so, include the registration number) 
 
Note: An FEI number is a facility specific identifier. Thus, if a particular facility has 
already been assigned an FEI number (through registration of any commodity, 
GDUFA, PDUFA, BsUFA, etc.), you should not request a second FEI number for 
that location.  
 
To obtain a DUNS number: 
 
  DUNS numbers can be obtained, or DUNS information modified, through 
Dun & Bradstreets website:  
https://www.dnb.com/solutions/government/duns-number-request-guide.html 
 
  To find or verify a previously obtained FEI or DUNS number go to FDAs 
registration site for drug establishments: 
https://www.accessdata.fda.gov/scripts/cder/drls/default.cfm 
 
7.  If a facility is listed on Form FDA 356h or elsewhere in my application, will it be 
subject to a user fee?  
 
Form FDA 356h is not linked to the assignment of a user fee.  The function 
performed by the establishment determines the assessment of a user fee, not the 
inclusion of a facility on Form FDA 356h.   
 
If you have questions about user fee assessments, please review the various guidances 
specific to the relevant user fee program: GDUFA, PDUFA, MDUFA, and BsUFA.6  
 
Note: For PDUFA and BsUFA applications, as of October 1, 2017, manufacturing 
facilities/establishments referenced in NDAs and BLAs are no longer subject to user 
fees. 
                                                 
6 See https://www.fda.gov/forindustry/userfees/. 
  5  Contains Nonbinding Recommendations 
 
Module 3 Questions/Answers  
 
1.  What facility information should I list in Module 3? 
 
Module 3 should contain all facilities listed on Form FDA 356h, as well as research 
and development manufacturing and testing sites that generated data in support of the 
application.  This includes facilities that manufactured or tested any lots of the 
product. 
 
Module 3 should also contain testing labs that perform functions integral to the 
control strategy, including but not limited to characterization and comparability of 
molecules and analytical similarity.  This includes any testing sites that generate 
release data, stability testing to support the application, and commercial testing sites.  
 
For combination products7 only: 
 
  Provide a detailed list of all manufacturing facilities; what activities occur at 
the site (e.g., assembly filling, sterilization, testing, other); and what 
constituent parts are at the site (e.g., drug only, device only, both drug and 
device).  For each facility that has at least two different constituent part 
manufacturing operations (e.g., drug and device) identify which CGMP  
operating system is established at the site per 21 CFR 4.4(a).  
  For each facility manufacturing a single entity or co-packaged combination 
product8 that is subject to 21 CFR Part 4, identify which CGMP operating 
system approach is established.  
  If the CGMP operating system complies with 21 CFR 4.4(b), identify the 
elected approach (i.e., 21 CFR 4.4(b)(1) for full 21 CFR 211 compliance with 
additional 21 CFR 820 provisions, or 21 CFR 4.4(b)(2) for full 21 CFR 820 
compliance with additional 21 CFR 211 provisions). 
 
2.  Where should I list the facilities in Module 3? 
 
All manufacturing and control sites should be in either the drug substance (3.2.S.2.1) 
or drug product (3.2.P.3.1) sections of Module 3.  If you are not sure if the site should 
                                                 
7 For additional information, see guidance for industry Providing Regulatory Submissions in Electronic Format  
Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (July 
2019). When final, this guidance will represent the FDAs current thinking on this topic.  For the most recent 
version of a guidance, check the FDA Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.  
8 The CGMP requirements for constituent parts of cross-labeled combination products that are entirely manufactured 
at separate facilities are the same as those that would apply if these constituent parts were not part of a combination 
product (e.g., for a drug/device combination product, only parts 210 and 211 (21 CFR parts 210 and 211) would 
apply to the manufacture of the drug constituent part(s) of the cross-labeled combination product, and only part 820 
(21 CFR part 820) would apply to the device constituent part(s)). 
  6  Contains Nonbinding Recommendations 
be included, add it to Module 3.  If you do not know whether the site should be listed 
in the substance or product section, list it in the section that you think is the most 
applicable.  Failure to list a manufacturing facility in the application or listing a 
facility in an incorrect area (i.e., other than 3.2.S.2.1 and 3.2.P.3.1) could result in an 
extension to the review period.  
 
3.  Should I consolidate facility information in each respective section of Module 3 of an 
application? 
 
Yes.  To facilitate FDAs assessment and inspection planning process, the Agency 
recommends that you clearly identify all facilities associated with your application in 
a table format at the beginning of the relevant section in Module 3.  We also 
recommend that you include this summary table at the beginning of each relevant 
section in Module 2.  
 
FDA further recommends including the full establishment name and the 
establishment address where the manufacturing function is performed.  Include the 
FEI number and specific manufacturing operations and responsibilities for each 
facility, including type of testing and drug master file (DMF) number, if applicable. 
 
Additionally, FDA recommends that you provide the name and title of an onsite 
contact person, including their phone number, fax number, and email address.       
 
Each facility should be ready for an inspection at the time of submission.  If a facility 
is not ready for inspection, indicate when the facility will be ready for inspection. 
 
If you decide to use a table format, FDA recommends that you use the format below.   
 
Facility information: 
 
Drug 
FDA  Specific Manufacturing 
Master 
Establishment  Responsibilities  
Site Name  Site Address  File 
Identifier  or Type of Testing 
Number 
(FEI)   [Establishment Function] 
(if applicable) 
1.         
2.         
 
  7  Contains Nonbinding Recommendations 
Corresponding names and titles of each facilitys onsite contact: 
 
Onsite Contact  Phone and 
Site Name  Site Address  Email address 
(Person, Title)  Fax number 
1.         
2.         
 
4.  If I use a firm to develop analytical method(s), should I list these facilities in the 
application?   
 
Yes.  The information for such firms should be provided in Module 3 of the 
application.    
 
General Questions/Answers 
 
1.  If a DMF is referenced in my marketing application, should I list the facilities 
associated with the DMF in my NDA/ANDA application? 
 
Yes.  The facility information contained within a DMF properly incorporated by 
reference should be included on both Form FDA 356h and in Module 3 of the 
application, as appropriate.  The recommended placement of the DMF facility 
information in the application follows the same logic as any other facility that is not 
part of a DMF (see Question 1 under Form FDA 356h Questions/Answers for facility 
information to include on the Form FDA 356h and Question 1 under Module 3 
Questions/Answers for the facility information to include in Module 3.)  The Agency 
will consider all facilities that are listed in a DMF apply to the referencing NDA or 
ANDA application unless explicitly stated in the DMF Letter of Authorization (LOA) 
that only certain facilities will be used by the referencing application.   
 
The DMF LOA, which permits the Agency to review the DMF and permits the 
authorized party (i.e., the company or individual who submits an application or 
another DMF) to incorporate information from the DMF into an application or 
another DMF by reference, should specify which facilities will be utilized in the 
commericial manufacturing.  If the LOA specifies a subset of facilities that will be 
utilized in commericial manufacturing, then only these facilities should be listed in 
Form FDA 356h and in Module 3 of the application.  Absent this specificity, all 
facilities that could be potential sources of the materials for which the DMF is being 
referenced by the NDA/ANDA should be listed in the application.   
 
Facility withdrawals submitted in an amendment to the DMF should also be 
submitted on Form FDA 356h for referencing applications if the facilities were 
included on the applicants Form FDA 356h (see Question 4 under Form FDA 356h 
Questions/Answers). 
 
  8  Contains Nonbinding Recommendations 
2.  Do I need to list research and development or testing site DMF facilities that generate 
release data or stability testing data to support my NDA or ANDA?   
 
Yes.  If a facility referenced in a DMF is to be utilized for research and development 
or testing, this is considered part of the commercial control strategy and should be 
included in your application.  Thus, if you intend to accept a LOA from a DMF 
testing facility, we recommend that this facility be listed in your application.  The 
recommended placement of the DMF facility information in the application follows 
the same logic as any other facility that is not part of a DMF (see Question 1 under 
Form FDA 356h Questions/Answers for facility information to include on the Form 
FDA 356h and Question 1 under Module 3 Questions/Answers for the facility 
information to include in Module 3 of the application). 
   
3.  Should I list excipient testers in the application? 
 
In general, excipient testers do not need to be listed in the application.  FDA expects 
the drug product manufacturers to have adequate testing/controls in place to 
determine if the excipient meets established acceptance criteria per 21 CFR 211.84.  
However, if an excipient is considered critical to the drug product performance (e.g., 
liposomes), the testing facilities should be listed in Module 3. 
 
4.  Do I need to include crude heparin manufacturing sites? 
 
Yes.  All crude heparin manufacturing sites and heparin testing sites should be listed 
on Form FDA 356h and in Module 3.  If there are any changes in the crude heparin 
sites, inform FDA as soon as possible through an appropriate amendment or post-
marketing submission.  
 
5.  For a Priority ANDA where an applicant is eligible to pre-submit facility information 
(i.e. Pre-Submission Facility Correspondence, PFC), what facility information should 
I include on Form FDA 356h that accompanies this pre-submission? 
 
See the guidance for industry ANDAs: Pre-Submission of Facility Information 
Related to Prioritized Generic Drug Applications (Pre-Submission Facility 
Correspondence) (November 2019)9 for the facility information that should be 
submitted on Form FDA 356h. 
                                                 
9 When final, this guidance will represent the FDAs current thinking on this topic.  For the most recent version of a 
guidance, check the FDA Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.  
  9