Transcript SPL (Electronic Reg and Drug List)

SPL R4 :
Listing Terminology
& Lifecycle Management
CDR Vada Perkins, USPHS
FDA/CBER/OD
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Controlled Terminology and
Coding
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Improved access to product information by health
care providers and patients
Reduce medical errors and improve patient care
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Data integration/evaluation
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Improved functionality across different data systems
Immediate access to information
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Terminology
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FDA has been working with a number of
organizations to develop and maintain terminology
for electronic drug registration and listing.
Terms and codes used for electronic drug
registration and listing are available for use in the
SPL file at no cost.
Links to the different terminologies are available on
the FDA Web site.
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Terminology Maintenance Organizations
How to obtain the terms and codes used for
electronic drug registration and listing
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Source: Product Data Elements
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Health Level Seven (HL7): www.hl7.org/
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Standards developing organization accredited by the
American National Standards Institute (ANSI)
Support message standards for the exchange and
interoperability of electronic health records.
SPL specification was initially developed by a group
within the HL7 Regulated Clinical Research Information
Management Technical Committee
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SPL Terminology
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Terminology for Drug Establishment Registration and Drug Listing and Content of Labeling
Route of administration
Dosage form
Package type
Units of measure and units of presentation
Color
Shape
Coating
Size
Scoring
Imprint codes
Symbols
SPL DEA Schedule
Section headings
Code system object identifiers (OIDs)
Document Type including Content of Labeling Type
Time Units: Unified Code for Units of Measure (UCUM)
Substances/Unique Ingredient Identifiers (UNIIs)
Business Operation
Marketing Category
Marketing Status
Equivalence Codes
Flavor
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National Drug Code (NDC) System
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FDA maintains the NDC System as an identifier for drugs. The NDC is a 10
character identifier divided into three segments (labeler, product, and
package).
Three codes may be derived from the NDC: NDC Labeler Code, NDC
Product Code, and NDC Package Code
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NDC Labeler Code is a 4 or 5 digit code assigned by FDA to an individual
registrant or private label distributor who needs to create NDCs for drug
products they plan to market.
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NDC Product Code is an 8 or 9 character code that uniquely identifies a
drug product. The NDC Product Code consists of the NDC Labeler Code assigned
by FDA and a 3 or 4 character product segment selected by the company,
separated by a hyphen.
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NDC Package Code is a 10 character code that uniquely identifies a drug
product in final package form. The NDC Package Code consists of the
NDC Product Code and a 1 or 2 character package segment selected by
the company, separated by a hyphen.
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NDC
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Each marketed drug product in final package form has one NDC
Package Code.
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NDC Labeler Codes are requested through electronic registration
and listing using SPL Files
* In addition to the NDC System, FDA maintains the FDA
Submission Tracking System for providing unique identifiers for
applications (e.g., ANADA, ANDA, BLA, NADA, and NDA) and is
obtained by the applicant through the application process.
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United States Pharmacopeia (USP)
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FDA along with USP maintains the preferred names of
ingredients and the Unique Ingredient Identifiers (UNII) using the
FDA Substance Registration System (SRS).
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These names and identifiers are accessible through USP Web
site at http://www.usp.org and publications, the FDA Web site at
http://www.fda.gov/oc/datacouncil
and the NCI Thesaurus Web site at http://evs.nic.nih.gov.
*Additional ingredient identifiers may be requested though FDA
by sending a request to [email protected].
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FDA/Substance Registration System
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www.fda.gov/oc/datacouncil/SRS.htm
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Unique Ingredient Identifier (UNII)
 Active ingredient
 Active moiety
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Unique Ingredient Identifier (UNII) Codes
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Joint FDA/USP Substance Registration
System (SRS) to support health information
technology initiatives by generating unique
ingredient identifiers (UNIIs) for substances in
drugs, biologics, foods, and devices.
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Non-proprietary, free, unique, unambiguous,
alphanumeric identifier based on a
substance’s molecular structure and/or
descriptive information
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UNII Assignment
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In order to receive a UNII, an ingredient must
be a ‘substance’, which is defined as “Any
physical material that has a discrete
existence, irrespective of origin.” Products will
not be assigned a UNII.
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SPL: Product Data Elements
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Ingredients
 Active and inactive ingredient and active moiety
name and code (Unique Ingredient Identifier
(UNII) from FDA SRS)
 Active and inactive ingredient strength (NCI
Thesaurus, UCUM)
Dosage form (NCI Thesaurus)
Appearance (imprint, color, shape, size, score,
coating, symbol) (NCI Thesaurus and HL7)
Route of administration (NCI Thesaurus)
DEA schedule (NCI Thesaurus)
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SPL: Product Data Elements
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Product
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Proprietary and nonproprietary name and code
(FDA DRLS)
Packaging
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Package type (NCI Thesaurus), quantity and code
(FDA DRLS)
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National Cancer Institute (NCI)
Thesaurus
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www.nciterms.nci.nih.gov
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Published monthly
Covers vocabulary for clinical care and research
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National Cancer Institute
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NCI maintains a number of different terminologies used in electronic drug
registration and listing including:
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dosage form
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routes of administration
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package types
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DEA schedule
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product color
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product shape
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flavors
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business operations
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marketing
These codes on located in the NCI Thesaurus and may be accessed through
the NCI Web site at http://evs.nci.nih.gov and FDA web site at
http://www.fda.gov/oc/datacouncil/spl.html.
Additional terms and codes for use in registration and listing may be requested
though FDA by sending a request to [email protected].
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Dun and Bradstreet (D&B)
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Dun and Bradstreet assign and maintain the Data Universal Numbering System (DUNS) Number as an
identifier for businesses. Each business location (e.g., headquarters, branch, subsidiary, establishment,
importer, US agent) has its own unique DUNS Number.
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If the DUNS Numbers for a location is not known, it may be looked up or requested by going to the D&B
Web site at http://www.dnb.com.
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DUNS Numbers are assigned by D&B within 30 business days of a request without charge.
The following information on the business entity is used to obtain a new DUNS Number
from D&B:
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Full legal name of Business,
Business Address,
City, State,
Zip code,
Country,
Local Phone Number,
Name of CEO/Business Owner
Legal structure of the business (e.g., Corporation, Partnership),
Year Business Started
Primary Line of Business (e.g. pharmaceutical manufacturer),
Total Number of Employees (including principals, and part-time).
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The Unified Code for Units of Measures
(UCUM):
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www.regenstrief.org
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Code system intended to include all units of
measures being contemporarily used in
international science, engineering, and business
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Logical Observation Identifier Names and
Codes (LOINC®):
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www.loinc.org
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Code system for reporting laboratory and other clinical
observations
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Regenstrief Institute
The Regenstrief Institute maintains a number of different terminologies
used in electronic drug registration and listing including:
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document types
section headings
units of measure
These terminologies are located in the Logical Observation Identifiers
Names and Codes (LOINC) and Unified Codes for Units of Measure
(UCUM).
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Both of these terminologies are available at
http://www.regenstrief.org and at other locations.
*Send a request to [email protected] for additional terms and codes for use
in
registration and listing.
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National Archives and Records Administration
(NARA)
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NARA maintains the codes for FDA regulations in the Code of
Federal Regulations.
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The codes for the various regulations are available through the
NARA publications and at the Government Printing Office Web
site at http://www.gpoaccess.gov.
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SPL Terminology
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Terminology for Drug Establishment Registration and Drug Listing and Content of Labeling
Route of administration
Dosage form
Package type
Units of measure and units of presentation
Color
Shape
Coating
Size
Scoring
Imprint codes
Symbols
SPL DEA Schedule
Section headings
Code system object identifiers (OIDs)
Document Type including Content of Labeling Type
Time Units: Unified Code for Units of Measure (UCUM)
Substances/Unique Ingredient Identifiers (UNIIs)
Business Operation
Marketing Category
Marketing Status
Equivalence Codes
Flavor
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Term/Code Unavailable?
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If a term/code is unavailable, please contact
[email protected].
**Applicant can provide reference source(s)
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SPL Lifecycle Management
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NDC Labeler Code
Establishment Registration
Drug Listing/Content of Labeling
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NDC Labeler Code Assignment
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NDC Labeler Codes are assigned by FDA to
registrants and private label distributors
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NDC to be assigned to drug products for
marketing.
Electronic drug registration and listing uses SPL
files for managing NDC Labeler Code assignment
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NDC Labeler Code Request
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NDC Labeler Code request SPL file is NDC Labeler Code Request
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Document identifiers – These identifiers are used for tracking the different
versions of the document.
id – uniquely identifies a specific document. The id is a Globally Unique
Identifier (GUID)
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setId – uniquely identifies a group of versions of a document. The setId is
also a GUID. When there is a change in a document, the id changes but the
setId stays the same.
Version number – is used to track SPL files successfully processed by the
FDA system.
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Version number is increased for each subsequent SPL file successfully
submitted using the same setId.
Effective time – the date of the submission.
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NDC Labeler Code RequestValidation Error
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SPL file cannot be processed because it fails
validation
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a report on the validation error is sent from FDA to
the contact person
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Correct the error in the SPL file and resubmit the
SPL file using the same setId as the rejected SPL
file
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Corrections to a
Submitted NDC LCR File
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Edit the SPL file and submit the new SPL file
with:
new id
new version number
original setId
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Unused NDC Labeler Code
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NDC Labeler Code must be used to create a
NDC for a listed drug within 24 months of the
initial assignment
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Code will be reassigned
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NDC Labeler Code Information
Update
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Update the previous SPL file to include:
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new information without changing the other
existing information
submit the new SPL file using:
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new id
new version number
original setId.
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2nd NDC Labeler Code Request
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Only one NDC Labeler Code is associated
with each NDC Labeler Code request.
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Submit a separate SPL file with a different setId if
a second NDC Labeler Code is requested
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Establishment Registration
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Establishments are registered by the owners or operators of the
establishments (registrants).
Electronic drug registration and listing uses SPL files for
managing establishment registration
The document type used for registration include:
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Establishment registration
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No change notification
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Out of business notification.
**The registrant provides their business name and DUNS Number
and contact information.
**The type of contact information is the same as described in the
section on requesting a NDC Labeler Code.
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Initial Submission for Establishment
Registration
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Registrants include one or more
establishments for each Establishment
Registration SPL file
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Even if the establishments have been registered
in the past.
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Establishment Registration Validation Error
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SPL file can not be processed because it fails
validation
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Report on the validation error is transmitted from
FDA to the contact person.
Correct the error in the SPL file
Resubmit the SPL file using the same setId as the
rejected SPL file.
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Corrections to a
Submitted SPL File
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Edit the SPL file and submit the new SPL file
using:
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new id
new version number
original setId
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Update Information for a Registered
Establishment
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Update the previous SPL file to include:
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new information without changing the other
existing establishment registration information
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Submit the new SPL file using:
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new id
new version number
original setId
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Addition of New Establishment
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Update the previous SPL file to include:
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Information on a new establishment without changing the
information on the other establishments
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Submit the new SPL file using:
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new id
new version number
original setId
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Remove a Previously Registered Establishment
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Update the previous SPL file by removing the
specific establishment information without changing
the existing information on the other establishments
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Submit the new SPL file using:
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new id
new version number
original setId
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No Changes to Registration Information
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Update information once a year
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If no change, submit an SPL file with the
document type-No change notification
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new id
new version
the original setId.
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Registrant Out of Business
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Submit an SPL file with the document type: Out of
business notification using:
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new id
new version number
original setId
**Registrant and establishment information is not
included with a SPL with the document type Out of
business notification.
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Marketing Category
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Marketing category is included for each
product.
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If marketing category is a marketing application
(e.g., NDA, ANDA)
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If marketing category is a monograph
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Application Number is included.
Code of Federal Regulation citation is included.
If Bulk ingredient is included
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Master File number is included.
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Marketing Status
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Marketing status
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Describes the date when the SPL file is added to
the public repository of SPL files and,
When the SPL file is removed from the public
repository
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The expiration date of the last lot released to the
marketplace provides a date when the SPL file should
be removed.
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Product Characteristics
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Product characteristics may include:
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Color, size, shape, scoring and imprint (solid
forms), flavors, and general substances that the
product contains.
A standardized image of the solid dosage
form may be included.
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Obtained from the FDA for inclusion with the
listing information.
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Route of Administration
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The routes of administration approved for the
drug product are included.
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Content of Labeling
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The content of the labeling provided with drug
listing (e.g., package insert, consumer
labeling, carton labels and container labels) is
included in the same SPL file as the other
drug listing information.
Carton and container labels include the
content of the Drug Facts or equivalent for
animal drug products and the content of the
principal display panel including the image of
the entire label as a single jpg file.
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Drug Listing Release 3 SPL
Previously Submitted
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Update the previous SPL release 3 file to a SPL
release 4 file with the additional drug listing
information and submit a new SPL file using
new id
new version number
original setId
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Initial Drug Listing Submission
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The drug listing information is provided in a single SPL file even if
the drug products have been listed in the past
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More than one drug product are included in a single SPL file
when the products relate to the same content of labeling though
each drug product is included in only one SPL file
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Drug listing includes all jpg files associated with the content of
labeling
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Drug listing SPL file is separate from the SPL file for NDC
Labeler Code request and the SPL file for establishment
registration.
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SPL: Private Label
Distributor
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Private label distributor includes all of the information that would have
been supplied by the registrant to include:
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All establishments involved in the manufacturing and processing
of the drug product
Registrant does not submit a SPL file for this drug product.
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If the private label distributor chooses not to provide the SPL file
with the drug listing information, then the registrant provides the
SPL file.
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SPL Listing: Registrant
Lists a Drug for a PLD
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Private label distributor chooses not to provide the SPL file with
the drug listing information
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Registrant provides the SPL file to include:
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Name of the private label distributor as the labeler
Itself as the registrant
All establishments involved in the manufacturing and processing of
the drug.
** The drug listing information is provided in a single SPL file
even if the drug products have been listed in the past.
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SPL: Listing with More than One
Registrant
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More than one registrant is involved in manufacturing and
processing a single drug product (e.g., contract
manufacturers),
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Only one registrant provides the SPL file with the drug
listing information for the drug product
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The registrant who provides the SPL file includes:
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Own establishments
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All establishments of all other registrants involved
in the manufacturing and processing of the drug
product
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SPL: Listing for Bulk Ingredients
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Registrant provides the SPL file with the drug
listing information for the bulk drug
ingredients (e.g., active pharmaceutical
ingredient).
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SPL Listing: Registrant Using a
Marketed Bulk Ingredient
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The registrant provides the SPL file with the
drug listing information for its drug product
including the NDC Product Code for the
marketed bulk drug ingredient.
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SPL Listing: Registrant
Repacking or Relabeling a Marketed Drug
Product
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The repacker or relabeler provides the SPL
file with the drug listing information for its
drug product
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Includes the NDC Product Code for the source
marketed drug product
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Kit:
Two or More Drug Products
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The registrant or private label distributor
provides the SPL file with the drug listing
information for its kit.
Includes drug listing information for each drug
product in the kit (component)
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NDC Product Code
NDC Package Codes (if applicable)
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SPL: Drug Listing Validation Error
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SPL cannot be processed if it fails validation
(pass/fail)
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Report on the validation error transmitted from
FDA to the contact person
Correct the error in the SPL file
Resubmit the SPL file
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the same set Id as the rejected SPL file
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Correct a Mistake in Drug Listing SPL
File
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Edit the SPL file to correct the mistake and
submit the new SPL file
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new id
new version number
original setId
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Update Information for Electronic Drug
Registration and Listing
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Update the previous SPL file so it includes
the new information without changing the
other existing drug listing information
Submit the new SPL file
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new id
new version number
original setId
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Change in C of L Requiring Prior
Approval
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Only Content of Labeling that accompanies a
marketed drug product is used for electronic drug
registration and listing
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Content of Labeling requiring prior approval not
included
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The SPL file for the content of labeling requiring prior
approval uses the same setId as the SPL file used in
electronic registration and listing.
Upon approval, the revised content of labeling is included
in the SPL file provided for electronic registration and listing
as described when changing content of labeling not
requiring prior approval.
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Change in C of L Not Requiring Prior
Approval
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Update the previous SPL file by changing the
content of labeling without changing the other
existing drug listing information
Submit the new SPL file
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new id
new version number
original setId
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Add a Package Configuration
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Update the previous SPL file by adding the
new package configuration without changing
the other existing drug listing information
Submit the new SPL file
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new id
new version number
original setID
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Remove a Package Configuration
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Update the previous SPL file by removing the
specific package configuration without
changing the other drug listing information
Submit the new SPL file
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new id
new version number
original setId
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Add a Drug Product Strength
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Update the previous SPL file by adding the
information on the new drug product strength
without changing the other drug listing
information
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Submit the new SPL file
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new id
new version number
original setId
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Discontinue One of Multiple Drug Product
Strength
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Update the previous SPL file by removing the
information on the specific drug product
strength without changing the other drug
listing information
Submit the new SPL file
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new id
new version number
original setId
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Discontinue Final Drug Product
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Update the previous SPL file by changing the
marketing status of the remaining drug
product to “completed” and provide the
expiration date for the last lot marketed in the
appropriate SPL data elements
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FDA will remove the SPL file from the public
repository on the expiration date
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FDA Data Standards Council-Supporting
Documentation
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http://www.fda.gov/oc/datacouncil/spl.html
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Directions for obtaining the SPL standard and schema from HL7
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Links to the SPL FDA Implementation Guide, the companion document to
the HL7 SPL standard providing additional details on creating SPL files
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Link to the Guidance for Industry: Providing Regulatory Submissions in
Electronic Format - Content of Labeling
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Guidance for Industry: Providing Regulatory Submissions in Electronic
Format-Drug Establishment Registration and Drug Listing (Draft Guidance)
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Style sheet files for viewing SPL content of labeling files
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Thank You
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