The Technology of Structured Product Labeling

1. The Technology of Structured Product Labeling Presented by Robert H. Wallace 06 June 2004

2. Human-readable labeling content compatible across systems Faster dissemination of labeling to improve risk mgmt More efficient evaluation of labeling changes More coordinated data collection and storage Better support for analysis of data Improved interoperability with other systems Improved integration of clinical data Improved access by prescribers and consumers Support for retention of legacy product labeling Goals of SPL

3. To create an SPL-compliant package insert, you need the following: Code system IDs and vocabularies HL7 FDA LOINC Any additional codes Your company’s object identifier (OID) SPL schema Implementation guide (to put it all together) Creating an SPL Package Insert

4. Vocabularies for SPL sections, etc. are controlled by code systems Source organization for a code system is specified in SPL by ITU-T or ISO object identifiers (OIDs) OIDS are informative: 2 = ISO/ITU-T jointly assigned OID 2.16.840 = a US entity of some kind 2.16.840.1.113883.6.1 = root identifier for LOINC Source organizations establish code systems and vocabularies for specific domains – LOINC codes are for lab and clinical info (i.e., 34092-7 is the Clinical Studies section for an FDA Package Insert) SPL also expects the pharma’s OID on the document See the HL7 Data Types specification for detailed information about use of OIDs in HL7 standards Code Systems and OIDs

5. Making an SPL requires the XML schema Schema = a file defining structure, content, and organization of an XML document SPL schema has three intermingling parts – document attributes (SPL header), structured content (SPL body structures), and narrative block (SPL body) SPL Schema

6. Discrete information about the document Identifies the type of document and its origin for storage, document management, exchange between institutions, etc. Does not identify the product Usually not intended for “human readability” Each discrete piece usually consists of the content and possibly a code from a predefined code system Document Attributes

7. Document attribute categories for the SPL are: Document classification – All SPLs are DOCs in HL7-ese (LOINC codes) Document identification – IDs, setIDs, version #s, type Document time stamps – Creation date, approval date, etc. Document confidentiality – HL7 controlled vocabulary Document language – IETF controlled vocabulary Author – Document author or originator (optional, but…) Owner of Marketing Authority – Such as Lilly Legal Authenticator – Guarantor of accuracy Reviewer – Agency reviewer Document Attribute Categories

8. Document Attribute Example <author> <time value="20030106"/> <assignedEntity> <id extension="PH00017" root="2.16.840.1.113883.3.933"/> <representedOrganization> <name>Midwestern Pharmaceuticals</name> <addr>Metropolis, IN 46285, USA</addr> </representedOrganization> </assignedEntity> </author> Identifying the package insert source company

9. Discrete information about the product Product information uniquely identifies the drug or biologic described in the package insert Coded elements may stand alone or may point to text in the narrative block (in XML) Also not intended for “human readability” Each discrete piece usually consists of the content and a code from a predefined code system (commonly HL7, FDA, LOINC) Structured Content

10. Structured content categories for the SPL are: Observation – Important descriptive information about the product, like imprint code (usually controlled vocabulary) ObservationMedia – Multimedia pointer, i.e., to molecular structure graphic Drug product code – Such as NDC code Package type, quantity – Controlled vocabulary Controlled substance classification – Like DEA number Active ingredient Active moiety Inactive ingredient Labeled route of administration Proprietary name – Trade name Generic name – Nonproprietary name Structured Content Categories

11. Structured Content Example <subject> <manufacturedProduct> <manufacturedLabeledDrug> <name>Gemzar</name> <activeIngredient> <activeIngredientIngredientEntity> <code code="122111-03-9" codeSystem="2.16.840.1.113883.6.61" codeSystemName=“Chemical Abstract Service"/> <name>gemcitabine HCl</name> </activeIngredientIngredientEntity> </activeIngredient> . . . Identifying the package insert compound

12. Contains the actual content – text, tabular data, and graphics – that comprises a package insert The human-readable package insert Intended for rendering (displaying or printing) of the package insert HL7 doesn’t require the narrative block to be in XML … but agencies can (and FDA will) Although it’s not called structured, the narrative block still has complex mark-up Narrative Block

13. Narrative block markup for the SPL includes: Content – High-level “wrapper” for narrative text Link – Similar to a hypertext link on the Web Delete and insert – Indicates change from previous version Subscript and superscript Line break – Line control (soft break), not a paragraph mark renderMultiMedia – Place for graphic to appear in narrative Paragraph List – Ordered (numbered) or unordered (bulleted) lists Table – Modified XHTML table model (similar to Web pages) Caption – Can label any other block structure Narrative Block Markup

14. Narrative Block Example <component> <section> <id extension="a123" root="2.16.840.1.113883.3.933"/> <code code="34089-3" codeSystem="2.16.840.1.113883.6.1" codeSystemName="LOINC" displayName="Description"/> <title>DESCRIPTION</title> <text> <paragraph>Gemzar&#174; (gemcitabine HCl) is a nucleoside analogue that exhibits antitumor activity. <content emphasis="bold">Gemcitabine HCl </content> is 2'-deoxy-2',2'-difluorocytidine monohydrochloride (&#223;-isomer). . . . </paragraph> </text> </section> </component> Identifying the Description Section

15. Rendering of an SPL-compliant file usually presents only the narrative block Narrative block contains all the text we think of as “labeling” SPL has an associated Web browser-compatible rendering as the “standard” view SPL will have an separate browser-compatible rendering for the structured content as well Rendering

16. Rendering an SPL-compliant package insert in a Web browser requires: The SPL file itself – drugapil.xml Files for any graphic that appears in the SPL file The SPL stylesheet files – currently called SPL.xsl and SPL.css Rendering Requirements

17. Examples of labels as viewed in Microsoft Internet Explorer v. 6.0x and the draft SPL stylesheet: Add/delete Tables Headings Font effects Lists Graphics Rendering Examples

18. Add and Delete

19. Tables

20. Headings

21. Headings

22. Font Effects

23. Lists

24. Lists

25. Graphics

26. Graphics

27. Modeling, Stylesheets – contact HL7 RCRIM Can’t model a label correctly in SPL Label as rendered in stylesheet changes the meaning of the content HL7 Implementation Guide is inaccurate Implementation – contact FDA FDA-specific implementation questions (i.e., how do I send my SPL to the FDA?) Addressing Issues

28. XML A markup language used to define elements of information that can be shared among applications and organizations. HL7 Health Level 7: An ANSI-accredited standards developing organization LOINC Logical Observation Identifiers Names and Codes: A code system managed by the Regenstrief Institute; LOINC codes serve as universal identifiers for clinical observations, including FDA package insert sections Structured Product Labeling An HL7 standard that addresses drug product labeling markup SPL body Also called SPL narrative block, the SPL body is labeling content that visually makes up the bulk of the package insert but is not “structured” per se SPL header Also called SPL document attributes, the SPL header is the “metadata” for the SPL document, denoting information about the origin of the SPL instance, such as its sender SPL structured content Text organized according to a predefined set of rules (schema) and in which each discrete piece of content is identified according to previously established definitions (schema and code systems) SPL - terminology