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
Improved access to product information by health care providers and patients Reduce medical errors and improve patient care Data integration/evaluation Improved functionality across different data systems Immediate access to information 2
Terminology
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. 3
Terminology Maintenance Organizations How to obtain the terms and codes used for electronic drug registration and listing 4
Source: Product Data Elements
Health Level Seven (HL7): www.hl7.org/ 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 5
SPL Terminology
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 6
National Drug Code (NDC) System
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
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.
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.
NDC Package Code NDC Product Code
is a 10 character code that uniquely identifies a drug product in final package form. The NDC Package Code consists of the and a 1 or 2 character package segment selected by the company, separated by a hyphen. 7
NDC
Each marketed drug product in final package form has one
NDC Package Code
.
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)
FDA along with USP maintains the preferred names of ingredients and the
Unique Ingredient Identifiers (UNII)
using the FDA Substance Registration System (SRS).
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
www.fda.gov/oc/datacouncil/SRS.htm
Unique Ingredient Identifier (UNII)
Active ingredient
Active moiety
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Unique Ingredient Identifier (UNII) Codes
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.
Non-proprietary, free, unique, unambiguous, alphanumeric identifier based on a substance’s molecular structure and/or descriptive information 11
UNII Assignment
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. 12
SPL: Product Data Elements
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) 13
SPL: Product Data Elements
Product
Proprietary and nonproprietary name and code (FDA DRLS)
Packaging
Package type
(FDA DRLS) (NCI Thesaurus), quantity and code 14
National Cancer Institute (NCI) Thesaurus www.
nciterms.nci.nih.gov
Published monthly Covers vocabulary for clinical care and research 15
National Cancer Institute
NCI maintains a number of different terminologies used in electronic drug registration and listing including:
dosage form routes of administration package types DEA schedule product color product shape flavors business operations 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)
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
.
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
.
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:
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): www.regenstrief.org
Code system intended to include
all
units of measures being contemporarily used in international science, engineering, and business 18
Logical Observation Identifier Names and Codes (LOINC®): www.
loinc.org
Code system for reporting laboratory and other clinical observations 19
Regenstrief Institute
The Regenstrief Institute maintains a number of different terminologies used in electronic drug registration and listing including:
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). 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)
NARA maintains the codes for FDA regulations in the
Code of Federal Regulations
. 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
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 22
Term/Code Unavailable?
If a term/code is unavailable, please contact [email protected]
.
**
Applicant can provide reference source(s) 23
SPL Lifecycle Management
NDC Labeler Code Establishment Registration Drug Listing/Content of Labeling 24
NDC Labeler Code Assignment
NDC Labeler Codes are assigned by FDA to registrants and private label distributors NDC to be assigned to drug products for marketing. Electronic drug registration and listing uses SPL files for managing
NDC Labeler Code
assignment 25
NDC Labeler Code Request
NDC Labeler Code request SPL file is
NDC Labeler Code Request
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)
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. 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 Request Validation Error
SPL file cannot be processed because it fails validation a report on the validation error is sent from FDA to the contact person Correct the error in the SPL file and resubmit the SPL file using the same
setId
as the rejected SPL file 27
Corrections to a Submitted NDC LCR File
Edit the SPL file and submit the new SPL file with:
new
id
new
version number
original
setId 28
Unused NDC Labeler Code
NDC Labeler Code must be used to create a NDC for a listed drug within 24 months of the initial assignment Code will be reassigned 29
NDC Labeler Code Information Update
Update the previous SPL file to include: new information without changing the other existing information submit the new SPL file using:
new
id
new
version number
original
setId.
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2
nd
NDC Labeler Code Request
Only one NDC Labeler Code is associated with each NDC Labeler Code request.
Submit a separate SPL file with a different setId if a second NDC Labeler Code is requested 31
Establishment Registration
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:
Establishment registration No change notification 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
Registrants include one or more establishments for each Establishment Registration SPL file Even if the establishments have been registered in the past.
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Establishment Registration Validation Error
SPL file can not be processed because it fails validation 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.
34
Corrections to a Submitted SPL File
Edit the SPL file and submit the new SPL file using:
new
id
new
version number
original
setId 35
Update Information for a Registered Establishment
Update the previous SPL file to include: new information without changing the other existing establishment registration information Submit the new SPL file using:
new
id
new
version number
original
setId 36
Addition of New Establishment
Update the previous SPL file to include: Information on a new establishment without changing the information on the other establishments Submit the new SPL file using:
new
id
new
version number
original
setId 37
Remove a Previously Registered Establishment
Update the previous SPL file by removing the specific establishment information without changing the existing information on the other establishments Submit the new SPL file using:
new
id
new
version number
original
setId 38
No Changes to Registration Information
Update information once a year If no change, submit an SPL file with the document type-No change notification
new
id
new
version the
original
setId. 39
Registrant Out of Business
Submit an SPL file with the document type: Out of
business notification
using:
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
Marketing category
is included for each product.
If m
arketing category is a marketing application (e.g., NDA, ANDA)
Application Number
is included.
If
marketing category is a monograph
Code of Federal Regulation citation
is included.
If Bulk ingredient is included
Master File
number is included.
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Marketing Status
Marketing status 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 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
Product characteristics may include:
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. Obtained from the FDA for inclusion with the listing information.
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Route of Administration
The routes of administration
approved
drug product are included.
for the 44
Content of Labeling
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.
45
Drug Listing Release 3 SPL Previously Submitted
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 46
Initial Drug Listing Submission
The drug listing information is provided in a single SPL file even if the drug products have been listed in the past 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 Drug listing includes all jpg files associated with the content of labeling 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
Private label distributor includes all of the information that would have been supplied by the registrant to include: All establishments involved in the manufacturing and processing of the drug product Registrant does
not
submit a SPL file for this drug product. If the private label distributor chooses not to provide the SPL file with the drug listing information, then the registrant provides the SPL file. 48
SPL Listing: Registrant Lists a Drug for a PLD
Private label distributor chooses not to provide the SPL file with the drug listing information Registrant provides the SPL file to include: 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.
49
SPL: Listing with More than One Registrant
More than one registrant is involved in manufacturing and processing a single drug product (e.g., contract manufacturers), Only one registrant provides the SPL file with the drug listing information for the drug product The registrant who provides the SPL file includes: Own establishments All establishments of all other registrants involved in the manufacturing and processing of the drug product 50
SPL: Listing for Bulk Ingredients
Registrant provides the SPL file with the drug listing information for the bulk drug ingredients (e.g., active pharmaceutical ingredient). 51
SPL Listing: Registrant Using a Marketed Bulk Ingredient
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. 52
SPL Listing: Registrant Repacking or Relabeling a Marketed Drug Product
The repacker or relabeler provides the SPL file with the drug listing information for its drug product Includes the NDC Product Code for the source marketed drug product 53
Kit: Two or More Drug Products
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) NDC Product Code NDC Package Codes (if applicable) 54
SPL: Drug Listing Validation Error
SPL cannot be processed if it fails validation (pass/fail) Report on the validation error transmitted from FDA to the contact person Correct the error in the SPL file Resubmit the SPL file the
same
set Id as the rejected SPL file 55
Correct a Mistake in Drug Listing SPL File
Edit the SPL file to correct the mistake and submit the new SPL file
new
id
new
version number
original
setId 56
Update Information for Electronic Drug Registration and Listing
Update the previous SPL file so it includes the new information without changing the other existing drug listing information Submit the new SPL file
new
id
new
version number
original
setId 57
Change in C of L Requiring Prior Approval
Only Content of Labeling that accompanies a marketed drug product is used for electronic drug registration and listing Content of Labeling requiring prior approval not included 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.
58
Change in C of L Not Requiring Prior Approval
Update the previous SPL file by changing the content of labeling without changing the other existing drug listing information Submit the new SPL file
new
id
new
version number
original
setId 59
Add a Package Configuration
Update the previous SPL file by adding the new package configuration without changing the other existing drug listing information Submit the new SPL file
new
id
new
version number
original
setID 60
Remove a Package Configuration
Update the previous SPL file by removing the specific package configuration without changing the other drug listing information Submit the new SPL file
new
id
new
version number
original
setId 61
Add a Drug Product Strength
Update the previous SPL file by adding the information on the new drug product strength without changing the other drug listing information Submit the new SPL file
new
id
new
version number
original
setId 62
Discontinue One of Multiple Drug Product Strength
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
new
id
new
version number
original
setId 63
Discontinue Final Drug Product
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 FDA will remove the SPL file from the public repository on the expiration date 64
FDA Data Standards Council-Supporting Documentation
http://www.fda.gov/oc/datacouncil/spl.html
Directions for obtaining the SPL standard and schema from HL7 Links to the SPL FDA Implementation Guide, the companion document to the HL7 SPL standard providing additional details on creating SPL files Link to the
Guidance for Industry: Providing Regulatory Submissions in Electronic Format - Content of Labeling
Guidance for Industry: Providing Regulatory Submissions in Electronic Format-Drug Establishment Registration and Drug Listing (Draft Guidance)
Style sheet files for viewing SPL content of labeling files 65
Thank You
66