Electronic Submission of Lot 
Distribution Reports 
 
 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-7800, or email ocod@fda.hhs.gov, or 
from the Internet at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/default.htm. 
   
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above or (CDER) Office of Communications, Division of Drug Information at 
301-796-3400. 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
Center for Drug Evaluation and Research 
March 2015 
 
   
Electronic Submission of Lot 
Distribution Reports 
 
 
 
Guidance for Industry 
 
 
Additional copies are available from: 
Office of Communication, Outreach, and Development 
WO71, Room 3128  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave. 
Silver Spring, MD 20993 
Phone: 800-835-4709 or 240-402-7800 
ocod@fda.hhs.gov  
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/default.htm   
 
or 
 
Office of Communications 
Division of Drug Information  
WO51, Room 2201 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave. 
Silver Spring, MD 20993 
Phone: 301-796-3400; Fax: 301-847-8714 
druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
Center for Drug Evaluation and Research  
March 2015 Contains Nonbinding Recommendations 
 
 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  LOT DISTRIBUTION REPORTS .................................................................................. 2 
IV.  PROCESS .......................................................................................................................... 3 
V.  WAIVER REQUESTS ..................................................................................................... 4 
A.  Content of Waiver Requests ................................................................................ 4 
B.  Where to Submit Waiver Requests ..................................................................... 5 
C.  FDA Response to Waiver Requests ..................................................................... 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The technical specifications associated with this guidance entitled Structured Product Labeling 
Implementation Guide with Validation Procedures is provided in a separate document and is 
updated periodically.  The technical specifications document is incorporated by reference into 
this guidance document.  To ensure that you have the most recent version of the technical 
specifications document, check the CBER Electronic Submissions Web page at: 
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. 
 
 
i 
  Contains Nonbinding Recommendations 
 
 
 
 
Electronic Submission of Lot Distribution Reports 
 
 
Guidance for Industry 
 
This guidance represents the Food and Drug Administrations (FDAs or Agencys) current 
thinking on this topic.  It does not create or confer any rights for or on any person and does not 
operate to bind FDA or the public.  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 using the contact 
information on the title page of this guidance. 
 
 
I.  INTRODUCTION 
 
This guidance provides you, licensed manufacturers of products distributed under an approved 
biologics license application (BLA) (henceforth referred to as applicants), with recommendations 
on how to submit lot distribution reports (LDRs) for biological products in an electronic format 
that FDA can process, review, and archive. 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe FDAs 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 FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
1  Contains Nonbinding Recommendations 
 
 
II.  BACKGROUND 
 
On June 10, 2014, FDA issued a final rule which, among other things, amended the requirements 
as to biological LDRs required under Title 21 of the Code of Federal Regulations 600.81 (21 
CFR 600.81).  Specifically, under this rule, applicants are required to submit LDRs to FDA in an 
electronic format that the Agency can process, review and archive (79 FR 33072).  This 
reporting requirement is effective as of June 10, 2015.1  Note that the rule does not change the 
content of these reports.   
 
In addition, 21 CFR 600.81 provides that the Agency will issue guidance on how to provide the 
electronic submission (e.g., method of transmission, media, file formats, preparation and 
organization of files).  The purpose of this guidance is to provide that information.  This 
guidance represents the Agencys current thinking on this topic.   
 
For example, as discussed later in this document, the guidance sets forth the Structured Product 
Labeling (SPL) standard and vocabulary for electronic submission of LDRs.  Within this 
guidance, you also are directed to additional resources, such as an implementation guide, 
validation procedures, and links with further information.  Note that we recommend using the 
same message exchange format that is currently used for establishment registration and drug 
product listing 
(http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm).  
 
FDA is developing links between the Center for Biologics Evaluation and Researchs (CBERs) 
lot distribution database and FDAs Adverse Event Reporting System (FAERS) and Vaccine 
Adverse Event Reporting System (VAERS) databases.  We anticipate that this linkage will allow 
for better monitoring of safety patterns by product lot.   
 
 
III.  LOT DISTRIBUTION REPORTS  
 
Under 21 CFR 600.81, applicants must submit to CBER or to the Center for Drug Evaluation and 
Research (CDER), as appropriate, LDRs containing certain specified information every 6 months 
about the quantity of the product distributed under their BLAs (including to distributors).  As 
needed, FDA may require an applicant to submit more detailed product distribution information.  
                                                 
1 Section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 379k-1), added by section 
1136 of the Food and Drug Administration Safety and Innovation Act (Pub. L. 112-144), provides that submissions 
under section 505(b), (i), or (j) of the FD&C Act or section 351(a) or (k) of the Public Health Service Act shall be 
submitted in such electronic format as specified by FDA in guidance.  In section 745A(a), Congress granted explicit 
statutory authority to FDA to implement the electronic format for submissions requirement by guidance.  This grant 
of authority, however, does not preclude FDA from implementing such requirements by notice and comment 
rulemaking (5 U.S.C. 553).  Accordingly, at this time, even though FDA has concluded that certain submissions that 
are addressed in the rule entitled Postmarketing Safety Reports for Human Drug and Biological Products; 
Electronic Submission Requirements are also within the scope of section 745A(a), FDA has determined that it is 
appropriate to amend the regulations on the submission of certain reports to remove references to paper submissions 
and to specify that such reports be submitted in an electronic format that FDA can process, review, and archive.  
FDA may consider, at a future date, whether to include information pertaining to submission of reports in electronic 
format in guidance pursuant to section 745A(a) of the FD&C Act. 
2  Contains Nonbinding Recommendations 
 
 
Furthermore, upon written notice, the Agency may request distribution reports at times other 
than every 6 months.   
 
The following link lists the elements to be included when you submit your electronic LDRs for 
each final container lot distributed during the reporting period - Structured Product Labeling 
Implementation Guide with Validation Procedures. 
 
Where feasible, parameter values for each field should be drawn from FDAs electronic data 
standards for SPL Resources.  The most current information on these electronic data standards is 
located at 
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.   
 
If an appropriate value does not appear to meet the needs for a particular product, you should 
submit a request for additional values to spl@fda.hhs.gov. 
 
 
IV.  PROCESS 
 
The lot distribution file should be included in eCTD Module 3, section 3.2.R Regional 
Information.  Applicants should name the leaf title, Lot-Distribution-Report-[Date of the 
submission].  The lifecycle for this file should be updated as appropriate, in accordance with the 
current eCTD2 specification. 
 
Lot distribution files should be formatted in the same electronic messaging standard used for 
drug registration and listing information and for the content of labeling for BLAs.  This standard, 
known as Health Level Seven (HL7) Structured Product Labeling (SPL), allows information to 
be exchanged, searched, and combined with other data sources in a manner that supports health 
information technology initiatives to improve patient care.   
 
Required information may be created using the following information to generate a Lot 
Distribution SPL file:  
 
A free tool for generating SPL files is available at  
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm189651.htm. 
 
Step-by-step instructions for electronically creating, validating, and submitting self-identification 
information are available at 
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm; or 
software tools developed internally by generic manufacturers utilizing the SPL technical 
specifications.   
 
Additional information is available at 
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. 
                                                 
2 eCTD guidance and specifications are available at 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/uc
m153574htm.  
3  Contains Nonbinding Recommendations 
 
 
Once a Lot Distribution SPL file is created and finalized, the file should be transmitted to FDA 
as a BLA eCTD submission through the Electronic Submissions Gateway (ESG), FDAs 
electronic information portal.  Information on the ESG is available at 
http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/default.htm. 
 
If any questions arise, you should call 240-402-8622 or communicate via email to 
LDD@fda.hhs.gov.  
 
 
V.  WAIVER REQUESTS 
 
Under 21 CFR 600.90, an applicant required to submit an LDR under 21 CFR 600.81 may ask 
FDA to waive temporarily the requirement that the report be submitted in electronic format.  We 
anticipate that temporary waivers from the electronic submission requirement will be needed 
only in rare circumstances.  Companies experiencing technical difficulties with transmission of 
their electronic submissions to FDA should consult FDA for technical assistance rather than 
submitting a waiver request.   
 
A.  Content of Waiver Requests 
 
Under 21 CFR 600.90(a), an applicants request to waive the electronic format 
requirement must include one of the following as supporting documentation:  An 
explanation why the applicants compliance with the requirement is unnecessary or 
cannot be achieved (e.g., acts of nature, widespread internet outages, temporary issues 
with the manufacturers database(s)); a description of an alternative submission format 
that satisfies the purpose of the requirement; or other information justifying a waiver. 
 
We recommend that this request be submitted to FDA in writing by mail.  The request 
should reference all products that are to be covered by the waiver.  If not already 
provided as justification for the waiver for purposes of meeting the requirements under 
21 CFR 600.90(a), the waiver request should include the reason for the request (i.e., the 
nature of the inability to comply), and the anticipated time to recover.  The waiver 
request also should include a proposed end date for the waiver and a description of any 
proposed alternative reporting method, as relevant to the circumstances.  Potential 
alternative reporting methods could include (but are not limited to) physical media and 
fax.  The waiver request should be clearly titled WAIVER REQUEST  LOT 
DISTRIBUTION REQUIREMENTS in bold capital letters at the top of the first page 
of the submission.   
 
4  Contains Nonbinding Recommendations 
 
 
B.  Where to Submit Waiver Requests 
 
For licensed biological products regulated by CDER, waiver requests should be 
addressed to: 
 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Therapeutics Biological Products Document Room 
5901-B Ammendale Road 
Beltsville, MD 20705-1266 
 
For licensed biological products regulated by CBER, waiver requests should be addressed 
to: 
 
Document Control Center  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Avenue 
Building 71, Room G112 
Silver Spring, MD  20993-0002 
 
C.  FDA Response to Waiver Requests 
 
FDA reviews waiver requests on a case-by-case basis.  FDA intends to respond in writing 
to the requestor,3 stating whether or not the waiver is granted.  If the waiver is granted, 
FDA intends to also include in its response letter a description of the alternate submission 
method(s) the Agency intends to accept.  Waivers of the requirement to submit 
reports in electronic format, if granted, will be temporary. 
 
                                                 
3 To follow up with the company, FDA intends to contact the individual who submitted the waiver request unless an 
alternate contact person is provided. 
5