The Technology of Structured Product Labeling Presented by

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

Goals of SPL 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 SPL Technology Presentation 2

Creating an SPL Package Insert To create an SPL-compliant package insert, you need the following: Code system IDs and vocabularies HL 7 FDA LOINC Any additional codes Your company’s object identifier (OID) SPL schema Implementation guide (to put it all together) SPL Technology Presentation 3

Code Systems and OIDs 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 HL 7 Data Types specification for detailed information about use of OIDs in HL 7 standards SPL Technology Presentation 4

SPL Schema 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 Technology Presentation 5

Document Attributes 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 SPL Technology Presentation 6

Document Attribute Categories Document attribute categories for the SPL are: Document classification – All SPLs are DOCs in HL 7 -ese (LOINC codes) Document identification – IDs, set. IDs, version #s, type Document time stamps – Creation date, approval date, etc. Document confidentiality – HL 7 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 SPL Technology Presentation 7

Document Attribute Example <author> <time value="20030106"/> <assigned. Entity> <id extension="PH 00017" root="2. 16. 840. 1. 113883. 3. 933"/> <represented. Organization> <name>Midwestern Pharmaceuticals</name> <addr>Metropolis, IN 46285, USA</addr> </represented. Organization> </assigned. Entity> </author> SPL Technology Presentation Identifying the package insert source company 8

Structured Content 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 HL 7, FDA, LOINC) SPL Technology Presentation 9

Structured Content Categories Structured content categories for the SPL are: Observation – Important descriptive information about the product, like imprint code (usually controlled vocabulary) Observation. Media – 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 SPL Technology Presentation 10

Structured Content Example <subject> <manufactured. Product> <manufactured. Labeled. Drug> <name>Gemzar</name> <active. Ingredient. Entity> <code="122111 -03 -9" code. System="2. 16. 840. 1. 113883. 6. 61" code. System. Name=“Chemical Abstract Service"/> <name>gemcitabine HCl</name> </active. Ingredient. Entity> </active. Ingredient> . . . SPL Technology Presentation Identifying the package insert compound 11

Narrative Block 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 HL 7 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 SPL Technology Presentation 12

Narrative Block Markup 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 render. Multi. Media – 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 13 SPL Technology Presentation

Narrative Block Example <component> <section> <id extension="a 123" root="2. 16. 840. 1. 113883. 3. 933"/> <code="34089 -3" code. System="2. 16. 840. 1. 113883. 6. 1" code. System. Name="LOINC" display. Name="Description"/> <title>DESCRIPTION</title> <text> <paragraph>Gemzar® (gemcitabine HCl) is a nucleoside analogue that exhibits antitumor activity. <content emphasis="bold">Gemcitabine HCl </content> is 2'-deoxy-2', 2'-difluorocytidine monohydrochloride (ß -isomer). . </paragraph> </text> </section> </component> SPL Technology Presentation Identifying the Description Section 14

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 SPL Technology Presentation 15

Rendering Requirements 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 SPL Technology Presentation 16

Rendering Examples of labels as viewed in Microsoft Internet Explorer v. 6. 0 x and the draft SPL stylesheet: Add/delete Tables Headings Font effects Lists Graphics SPL Technology Presentation 17

Add and Delete SPL Technology Presentation 18

Tables SPL Technology Presentation 19

Headings SPL Technology Presentation 20

Headings SPL Technology Presentation 21

Font Effects SPL Technology Presentation 22

Lists SPL Technology Presentation 23

Lists SPL Technology Presentation 24

Graphics SPL Technology Presentation 25

Graphics SPL Technology Presentation 26

Addressing Issues Modeling, Stylesheets – contact HL 7 RCRIM Can’t model a label correctly in SPL Label as rendered in stylesheet changes the meaning of the content HL 7 Implementation Guide is inaccurate Implementation – contact FDA-specific implementation questions (i. e. , how do I send my SPL to the FDA? ) SPL Technology Presentation 27

SPL - terminology XML A markup language used to define elements of information that can be shared among applications and organizations. HL 7 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 HL 7 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) 28 SPL Technology Presentation