Electronic Submission of Lot Distribution Reports: Guidance for Industry

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

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

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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.

Contains Nonbinding Recommendations
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Electronic Submission of Lot Distribution Reports
Guidance for Industry
This guidance represents the Food and Drug Administration’s (FDA’s or Agency’s) 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.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe FDA’s current thinking on a topic, and should be
viewed only as recommendations unless specific regulatory or statutory requirements are cited.
The use of the word should in FDA’s guidances means that something is suggested or
recommended, but not required.

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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 Agency’s 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 Research’s (CBER’s)
lot distribution database and FDA’s 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.

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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 FDA’s 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 eCTD 2 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
m153574 htm.

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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), FDA’s
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 applicant’s request to waive the electronic format
requirement must include one of the following as supporting documentation: An
explanation why the applicant’s compliance with the requirement is unnecessary or
cannot be achieved (e.g., acts of nature, widespread internet outages, temporary issues
with the manufacturer’s 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.

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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.