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

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

4. 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.

5. 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

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

7. 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)

8. 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

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

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

11. 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…

12. 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…

13. 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

14. 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

15. 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

16. 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

17. 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)

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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

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

27. 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

28. Background Information
Metadata
Background Information On
Metadata

29. 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.

30. 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.

31. [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.

32. 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!
Subject Relationship Subject2
USPI v3 … … is based on …… USPI v1.