DIA Webinar
SPL R4 :
Electronic Drug Establishment
Registration and Drug Listing
September 9, 2008
LCDR 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
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Source: Drug Listing 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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National Cancer Institute (NCI) Thesaurus: www.nciterms.nci.nih.gov
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Published monthly
Covers vocabulary for clinical care and research
The Unified Code for Units of Measures (UCUM): 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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Source: Drug Listing Data
Elements (cont.)
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Logical Observation Identifier Names and
Codes (LOINC®): www.loinc.org
 Code
system for reporting laboratory and other
clinical observations
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FDA/SRS:
www.fda.gov/oc/datacouncil/SRS.htm
 Unique
Ingredient Identifier (UNII)
 Active ingredient
 Active moiety
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SPL: Drug Listing Data Elements
• Product
– Proprietary and nonproprietary name and code (FDA DRLS)
• Description
– 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)
• Packaging
– Package type (NCI Thesaurus), quantity and code (FDA DRLS)
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SPL Terminology
Verification
Terminology for Drug Establishment
Registration/Drug Listing and Content of
Labeling
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Drug Registration and Drug Listing and Content
of Labeling Terminology Lists in XML format –
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"Structured Product Labeling Validation
Procedures for Drug Establishment Registration
and Drug Listing"
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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 www.spl.fda.hhs.gov
**Applicant can provide reference source(s)
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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.
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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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Ingredients
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Ingredient name (substance name)
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Established name of ingredient (active and inactive)
 Source -FDA
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Ingredient code (substance code)
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Active moiety name (active moiety entity name)
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Unique Ingredient Identifier
Source –FDA Substance Registration System
Active portion of the active ingredient (without counter ion)
Source –FDA
Active moiety code (active moiety code)
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Unique Ingredient Identifier (UNII)
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Source –FDA Substance Registration System (SRS)
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Unique Ingredient Identifier
(UNII) Codes

FDA Notification of UNII codes via distribution
list to FDA Data Standards Council Listserv
members (updated monthly)
 Assigned
UNIIs for CBER legacy products:
Notification to Industry through formal regulatory
correspondence
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Confirmation of UNII Codes
Other DLDE requirements
Necessary to list electronically (June 2009)
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Important Information
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More information about UNII codes and
the SRS is available at:
 SRS@cder.fda.gov
 http://www.fda.gov/oc/datacouncil/SRS.htm
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Content of Labeling Requirement
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Health Level Seven (HL7) Structured Product Labeling (SPL) in XML to be
the only acceptable presentation in electronic format for the submission of
content of labeling
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CDER: In Effect (October 31, 2005)
CBER: beginning October 15, 2008
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Applies to the content of labeling with original submissions, supplements,
and annual reports.
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Content of labeling in SPL format is not required for annual reports unless
there are changes from the currently approved SPL labeling.
**Submit if this is the first time submitting to FDA in SPL format
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Memorandum to Docket 92S-0251
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Notification of FDA readiness to accept
electronic regulatory submissions for
content of labeling.
 Pursuant
to 21 CFR part 11.2(b)(2)
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Labeling
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Continue to submit Word version with SPL
labeling
 SPL
to PDF/Word Conversion Tool
Currently in testing
 Would eliminate the requirement to submit content
of labeling in Word
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16
FDA Data Standards CouncilSupporting 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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http://spl-work-group.wikispaces.com
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FDA Electronic Submissions
Gateway (ESG)
Courtesy of MICHAEL FAUNTLEROY,
FDA/CBER/OD
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What is the Gateway?
An Agency-wide solution and central transmission point for accepting
secure electronic regulatory submissions over the Internet.
The FDA ESG is a conduit, or "highway", along which submissions travel to
reach their final destination. It does not open or review submissions; it
automatically routes them to the proper FDA Center or Office.
Sponsor
Gateway acknowledgement sent
to sponsor
Electronic
Regulatory
Submission
Center
FDA ESG
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Gateway Cost
• The FDA does not charge for the use of ESG
• The only costs incurred should relate to following;
– Public Key Infrastructure (PKI) certificate
• Binds public keys with user IDs via a certificate authority
• duration of 1-3 years
• typically costs from $20-$30
– JAVA, which is available for free
– Cost of desktop support
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FDA Electronic Submission Gateway - Benefits
• Improves costs, resource requirements, and time efficiencies for
both Sponsors and the Agency
• Obviated need to burn CDs/DVDs or create tapes
• Eliminated QC of submission associated with creating media
• Eliminated courier fees associated with Regulatory submissions
• Provided a more efficient and secure transfer of electronic
submissions
• *Facilitates earlier receipt of the submission by the Agency and
access to the submission by the Reviewer
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Electronic Submissions Gateway Process Before You Register
• Submit a Letter of Non-Repudiation Agreement
– A letter of Non-Repudiation Agreement must be submitted to the
FDA. The non-repudiation agreement allows the FDA to receive
electronically signed submissions in compliance with 21 Code of
Federal Regulations (CFR) Part 11.100.
• Send letter to Office of Regional Operations, (ORO)
• Send copy to ESG Project Manager
– Sample letters are on the FDA ESG website
• Obtain a Digital Certificate
– The FDA ESG uses digital certificates to secure the transaction and
communications.
– ESG website has information on how to obtain a digital certificate
• Determine Submission Method
– Web-based (WebTrader)
– Gateway-to-Gateway (B2B) submissions using industry standards
for the transport protocol (AS2)
– A separate registration will be required for each option selected
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ESG Account Registration and Setup Process
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Send an email request to esgprep@fda.gov , include the
submission method you intend to use, contact persons name
and company name is the email.
FDA will email back the registration information
Register online using the information provided
FDA will review the registration and activate the account
FDA will send an approval notification and guidelines for test
preparation
Complete the guidelines and send test submission
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ESG resources and contact information
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Website: http://www.fda.gov/esg/
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Registration Information
System Requirements
User Guide and Tutorials
Digital Signatures and Certificates
System Status and Help Desk
Links to submission guidelines
Email for preparation/Registration/Policy: esgprep@fda.gov
– This email is for question and help in setting up test and production
accounts
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Email for technical issues: esgreg@gnsi.com
– This email is for system and submission related issues
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FDA project manager: Michael Fauntleroy
– Email: michael.fauntleroy@fda.hhs.gov
– Phone: 301-827-5132
– Address: Office of the Director (HFM-25)
Center for Biologics Evaluation and Research
Food and Drug Administration
11400 Rockville Pike, Room 4119
Rockville, MD 20857
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