U.S. Food and Drug Administration Notice: Archived Document The content in this document is provided on the FDA’s website for reference purposes only. It was current when produced, but is no longer maintained and may be outdated.

Structured Product Labeling (SPL) CDR Vada Perkins, USPHS Regulatory Program Management Officer FDA/CBER/OD

BACKGROUND Federal Register of December 11, 2003 (68 FR 69009) FDA published final regulations requiring that the content of labeling be submitted electronically “in a form" that FDA can process, review, and archive. CDER announced in public docket number 92S-0251 the following new procedures for electronic submission of content of labeling, effective October 31, 2005: PDF is no longer a format FDA can use to accept the content of labeling submitted electronically. Applicants should use the SPL standard when submitting all labels, labeling supplements, and amendments to FDA in XML. 21 CFR Part 11 Electronic Records; Electronic Signatures; Final Rule Electronic Submissions; Establishment of Public Docket; Notice

CBER Notification http://www.fda.gov/oc/datacouncil/spl.html Subject: Docket 92S-0251 – Transmittal Effective Date: October 15, 2008 Notification established Health Level Seven (HL7) Structured Product Labeling (SPL) in XML as the only acceptable presentation in electronic format for the submission of the content of labeling Applicable to the content of labeling with original submissions, supplements, and annual reports. Regulatory citation: 314.50(l), 314.94(d), 601.14(b), 314.81(b).

Structured Product Labeling (SPL) Electronic labeling standard developed by Health Level 7 (HL7) Utilizes eXtensible Markup Language (XML) Machine readable tags to improve search functionality across systems Usability across multiple database platforms Promote electronic health information initiatives Enhance search capabilities

Current State Limited in: Readability Accessibility Usability paper labels and forms cannot be accessed by computer systems

Drug Registration and Listing (Paper) Forms (2656, 2657, 2658)

XML Structured Content <time value="20080207"/>       <assignedEntity>             <id extension=“VP00019" root="2.43.106.1.925856.8.422"/>             <representedOrganization>                   <name>Greatest Pharmaceuticals</name>                   <addr>Metropolis, MA, USA</addr>             </representedOrganization>       </assignedEntity> </author>  •SPL is created using Extensible Markup Language (XML) –similar to HTML for webpages •XML–Relatively human-legible –Machine readable–Tags (elements) permit search of key information •XML Documents –created via Notepad, Word Pad, XML editing tools, SPL authoring tools, SPL conversion services, Xforms, etc… •XSL Stylesheet –transforms the XML data to be viewed via web browser or printed documents

SPL Stylesheet View/Source Code Courtesy of Lonnie Smith, FDA

Benefits of SPL Improved access Computer Readable Information Systems Locate a specific section of the labeling and specific elements within labeling and product listing sections. Information Systems XML easily imported into information systems for other uses (e.g., data mining). Publicly available Content of Labeling is made available by the FDA thru NLM (DailyMed) to consumers and health care providers. http://dailymed.nlm.nih.gov/dailymed/about.cfm

Draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration and Drug Listing (7/11/08) Voluntary Pilot Program NDC Labeler Code Request Establishment Registration Drug Listing/Content of Labeling Guidance covers: How to submit the information electronically in Structured Product Labeling (SPL) files, using a defined terminology. Transition from paper-based to electronic submissions of drug establishment registration and drug listing information. What registration and listing information (including labeling) to submit. Test the performance of FDA’s electronic system for this type of submission. Mandatory (1 June 09)

FDA eLIST Inbound TRANSMIT (NLM Web) (Redacted Listing Files) DailyMed website FDA ESG Gateway eList Industry REPOSITORY . Pass VALIDATE PROCESS FDA Web (Redacted Listing Files) FACTS@FDA website Fail Outbound DATA FILES (Database Reports) Registration Listing ERROR MESSAGE NDC Directory & Establishments Websites VALIDATION ERRORS Validation of Structured Product Labeling Data Elements

Data Source – SPL Documents NDC LCR Listing/CoL Labeler Code: XXXXX Labeler DUNS #: 354898887 Labeler Code: XXXXX Labeler DUNS # 354898887 Establishment DUNS #(s) 111111111 Type of Operations Establishment Registration Establishment DUNS #(s) 111111111 Type of Operation(s) US Agent Importer(s) Courtesy of Lonnie Smith, FDA

SPL Terminology Only controlled terminology permitted in SPL. Terminology lists located on FDA Data Standards Council’s SPL web page: http://www.fda.gov/oc/datacouncil/spl.html

SPL Terminology Only controlled terminology is permitted in SPL documents Terminology lists are on FDA Data Standards Council’s SPL web page: http://www.fda.gov/oc/datacouncil/spl.html 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

Listserv FDA Data Standards Council Website http://www.fda.gov/oc/datacouncil/

Acknowledgements Lonnie Smith, FDA/Office of Critical Path Programs Randy Levin, MD, FDA/Office of Critical Path Programs

Thank You General Questions: vada.perkins@fda.hhs.gov