EDM Reference Model – Extensions for US Labeling Presenter: Pat Cowall-Hanover Eli Lilly and Company

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Outline EDM Reference Model EDM - Labeling Domain Labeling - Specific challenges Labeling Domain Metadata Next Steps

The DIA EDM Reference Model “The EDM Reference Model is a document management initiative aimed at developing a taxonomy/metadata reference model that can ultimately be shared by biopharmaceutical organizations as a common starting point for building sustainable, shareable EDM repositories.” It is focused on: documents and document management activities driven by regulatory submission requirements, particularly relating to the eCTD. It is being developed by several teams under an umbrella group sponsored by the DIA EDM SIAG.

The DIA EDM Reference Model Artifact: A document that is included in a submission. Associated with each artifact are properties (metadata elements). Metadata Categories: Submission Document Management Content Management Product Domain Specific Quality Non-Clinical Clinical Prescribe (aka Labeling) Pharmacovig Admin

Outline EDM Reference Model EDM - Labeling Domain Labeling - Specific challenges Labeling Domain Metadata Next Steps

Scope: Labeling Artifacts All types of product labeling Information that require regulatory approval PLUS… In all electronic formats, and Some related artifacts (eg, CCDS, global reference / justification documents) Content of Labeling - Scope includes: Healthcare professional (HCP) labeling Patient/consumer (PC) labeling Core labeling: CCDS and other global reference documents Carton and container labeling And potentially: Labeling history documents Development CDS Other documents used for RA discussion (eg, FDA TPP)

Labeling Domain Sub-group Team Members Lead: L. Fontaine Active Members: S. Bass, P. Cowall-Hanover, A. Howett, G. Saner, K. Thomas Status Project start: July 2008. Initial metadata identified for USPI USPI metadata definition/characterization ongoing

Outline EDM Reference Model EDM - Labeling Domain Labeling - Specific challenges Labeling Domain Metadata Next Steps

Labeling Model Labeling has concept of ….draft to final/approved …to submitted And … Submission(s) Internal Approval Draft 1 Draft 2 etc… Archive

Labeling Model Labeling has concept of ….draft to final/approved …to submitted Label is not a single document - multiple “editions” And…. First Edition Submission(s) V1.0 Approved Draft 0.1 Draft 0.2 etc… Archive Second Edition Draft 1.1 Draft 1.2 etc…

Labeling Model Labeling still has concept of ….draft to final/approved …to submitted Label is not a single document - multiple “editions” Branched flow of content – with complex relationships The final version of one “edition” is the basis of multiple simultaneous new “editions” First Edition Submission(s) V1.0 Approved Draft 0.1 Draft 0.2 etc… Archive Second Edition Draft 1.1 Draft 1.2 etc… Third Edition Draft 2.1 Draft 2.2 etc…

Labeling – What’s different about labeling (1) (aka Specific Challenges) “Document type” and “product identification” are complex. Product characteristics: unique identification and searching needs Product/generic name is not enough Need identifiers for formulation, strength, dosage form, package type, etc. Need product class level(s) – eg ATC Need product family level(s) – eg insulins, antihypertensives, oncolytics, etc. Labeling artifact types: granular Physician labeling, PPI, Medguide, User manual Container label, carton, blister foils 13

Labeling – What’s different about labeling (2) (aka Specific Challenges) Labeling documents live in a larger world than the eCTD submission. Parallel universes: Content of labeling exists in multiple formats and/or in multiple artifacts. e-content of labeling: .doc, .pdf, xml, html Printed version (“artwork”): special electronic formats for creating printed copy Printed version sometimes contains multiple artifacts – eg USPI and PPI SPL contains multiple artifacts – USPI, PPIs, packaging images Need to track the specific “edition” of the content of labeling (COL) text into all artifacts Larger universe: Relationships need to be tracked “Core” labeling – CCDS (company core data sheet) - Track “core” concepts to / from local and country-specific labeling documents For Generics: Reference label Supporting documentation 14

Labeling – What’s different about labeling (3) (aka Specific Challenges) Need to track complex relationships and status on multiple levels. Nested Life Cycle. Approval is needed on multiple levels Internal cross-functional working groups Corporate labeling committees Regulatory agencies Interlaced Workflows – Splitting (branching) and merging of workflows Need to track relationships between drafts and “editions” Parallel drafting - multiple (draft) documents maintained in parallel Multiple “active” versions of the label - reconciliation of new and “old” Merging of text from multiple drafts / “editions” “Versioning challenge” Publication / Implementation -- Multiple customers Corporate web site Regulatory authorities – eg. FDA Printed version (“artwork”) – included with marketed product Drug Listing (US) – NLM website Other - PDR, promotional / marketing materials 15

Compendial change+CBE Labeling: “Interlaced Workflow” A Regular CBE B Urgent CBE C PA - New indication D AR - Name change E and F Compendial change+CBE C cont. PA approved A α β γ 1 I a b c B 2 II C III D 3 E 4 IV F 5 V Team Approved Tech Editing Submitted to FDA Team Drafting Released for Publishing White = CBE Pink = PA, Prior Approval Green = Annual Report

Released for Publishing Team Drafting a a a a a a a Labeling: Publishing/printing b b b b b b b c c c c c c c Team Approved Published to Web A Web 1 B Web 2 C Web 3 D E Web 4 F Web 5 Tech Editing α α α α α α β β β β β β γ γ γ γ γ γ Submitted to FDA I II III IV V Released for Publishing 1 2 3 4 5 a b c 1 a b c 2 a b c 4 a b c 5 FPL Preparation * 2 4 5 Published to Pack *Currently no production scheduled (assumption: no repackaging required)

Outline EDM Reference Model EDM - Labeling Domain Labeling - Specific challenges Labeling Domain Metadata Next Steps

EDM Model: Base Metadata EDM Focus: eCTD taxonomy and document management Submission Document Management Content Management Product Name Application Creation Date Author Chemical Name Region Creator Business Owner Compound ID Submission Country Language Component Name Generic Name Application Type Litigation Hold Contributor Trade Name Submission Type Modify Date Document Title Procedure Type Status Issued Date Transaction Version Label CTD/Section Version Number Project Submit Date

Challenge: Document type and Product characterization Challenge: Artifact identification and searching Granularity of document types and product characteristics Searching across geographies Example = U.S. Patient Package Insert - Gooddrug 10 mg/ml Pen EDM Metadata: Labeling Domain Metadata: Artifact name (from eCTD) Document title Country Language Generic name Tradename Labeler Company name Product Descriptors: Additional Product identifiers 10 mg/ml, Pen Package characteristics Pack size of 1 Product family Insulins Product class ATC classification 20

Challenge: Nested Lifecycle Challenge: Each label has multiple possible customers for approval and publication / implementation Corporate/internal: labeling team (drafting), corporate approval committees, etc. Regulatory: initial submission, label negotiations, approved label Implementation: printed label, website, drug listing, publication Example: USPI - approved by regulatory authority, not yet published EDM Metadata: Labeling Domain Metadata: Status Corporate/Internal status Regulatory status Publication / Implementation / Listing status Each of the above would have fields associated with: Status - multiple values possible Date - for some nests 21

Challenge: Multiple formats and/or layouts Challenges: Some labeling artifacts are like “envelopes” that include multiple labeling artifacts Printed labels and SPL (drug listing) includes the USPI and PPI(s) “Envelopes” are published/implemented Artifacts and “envelopes” can be published/printed in different formats and “layouts” Different “artwork” because of paper size or folding Examples: “Artwork” has multiple layouts – eg one to be packaged with bottles and one to be packaged with blisters. They are folded differently and the title and barcode are positioned in different places based on the folding. EDM Metadata: Labeling Domain Metadata/Relationships: Artifact name Artifact presentation type - COL, printing, web, etc Artifact contains (ie what is in this “envelope”) Layout identifier (ie Item code) Electronic file extension (ie type of rendition) 22

Challenge: Interlaced workflow Challenges: Branching relationships. Multiple “active” labels exist at any one time. Active = versions that are allowed to be used in a next step (not out-dated or retired) Current = versions that are “in use” - depending on the context of use and “local” customs eg. Approved by FDA, implemented on web/print/etc Tracking COL text that is included in each “active” label Examples/questions: Approved: only one version is the most “current” approved by FDA Published: different labels are “current” – based on the customer Which “edition” of the label was used as the “basis” for this label change? What changes are included in this “edition” of the label? EDM metadata: Labeling Domain Metadata/Relationship: Project Version number Version label (???) Based on Key changes (not “track changes”) Approval type – CBE, PA, AR 23

Challenge: Relationship to other global labeling / references Challenge: Need to track relationship of COL to other key documents CCDS: company core data sheet Specific local label to and from corporate reference document Reference label Generics Example/question What labeling concepts are included in this USPI EDM metadata: Labeling Domain Metadata / Relationship Country Relationship to reference document - specific version of the CCDS, RL 24

EDM Model: Labeling Domain Submission Document Management Content Management Product Name Labeling Domain Application Creation Date Author Chemical Name Product /package identifiers Region Creator Business Owner Compound ID Labeler(s) Submission Country Language Component Name Generic Name Project Application Type Litigation Hold Contributor Trade Name Based on Submission Type Modify Date Document Title Key changes Procedure Type Status Issued Date Link to reference documents Transaction Version Label Artifact contains CTD/Section Version Number Artifact presentation type Layout identifiers (Item codes) Submit Date Approval type Internal status and dates Regulatory Publication status and dates

Outline EDM - Reference Model EDM - Labeling Domain Labeling - how is it different Labeling - Specific Metadata Next Steps

Labeling Domain: Next Steps Complete definition/characterization of USPI metadata clear definitions descriptions of how metadata is intended to be used areas of flexibility that would allow companies to adapt to their local environment. Expand discussion to include other US artifacts CCDS and EU-PIM Other 1 and 2 may be done in parallel 27

Background Information Metadata Background Information On Metadata

Metadata is used or is useful for: indexing and searching navigation What Is Metadata For? Metadata is used or is useful for: indexing and searching navigation collection organization process coordination and management Metadata is really about organizing content in relation to domain knowledge, so that each item can be found in every relevant context.

Metadata is data about data: What Is Metadata? Metadata is data about data: Prescriptive metadata defines a data element; e.g. Data element name (as program reference) Data type (number, character, etc.) Length (in bits, bytes or words or by function) Descriptive metadata carries information about a complex data element, such as a document; e.g. Title Author Subject The term ‘metadata’ is now used generally only to refer to descriptive metadata. This presentation follows that usage.

[Descriptive] Metadata are also known as: Document properties What Is Metadata? [Descriptive] Metadata are also known as: Document properties Metadata elements Predicates As well, the term ‘metadata’ is often used broadly to include the values that may be assigned to specific properties (i.e. elements or predicates) and also the structures used to organize these values, such as term list, taxonomy, thesaurus or ontology.

Defining Metadata and Relationships Metadata: The ‘triple’ form is a useful way to think about metadata. Subject . Predicate . Object This document … has a status of ….. Approved. Relationships between subjects (i.e. between resources or information artifacts) can also be expressed as triples -- but they are not the same as predicates! Subject1 . Relationship . Subject2 USPI v3 … … is based on …… USPI v1.