1. Paragon Solutions, Inc. Proprietary and Confidential
Practical Application of the
TMF Reference Model
Industry Webinar
November 14, 2012
Fran Ross, Principal Consultant, Paragon Solutions
Michael Agard, Senior Consultant, Paragon Solutions

2. Paragon Solutions, Inc. Proprietary and Confidential
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Agenda
Introductions
TMF Reference Model
• What is it and why do I need it?
• Where can I find the model and related information?
• How do I get involved?
Applying the Model
• Practical steps to implementation at your organization
Content Considerations
• Specific content type considerations for your eTMF improvements

3. Paragon Solutions, Inc. Proprietary and Confidential
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Paragon Solutions’ Introduction
Corporate Facts
• Privately owned,
30-year history
• Professional Services
and Solutions Divisions
• US-Based, NJ
Headquarters
- 8 domestic and
international offices
- Overseas development
center
• Dual-shore Delivery
Paragon is an enterprise information management
solutions company that helps firms leverage
information assets to achieve better business
results.

4. Paragon Solutions, Inc. Proprietary and Confidential
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Polling Question #1
1A. Level of involvement in TMF Reference Model?
a) Active member
b) Interested follower
c) Know a little
d) News to me
1B. Is your organization using the TMF Reference Model?
a) Yes, fully adopted
b) Working on it
c) Wishful thinking
d) Not likely
e) Don't yet know

5. Other business records
Why a TMF Reference Model?
Supporting records
generally outside TMF
e.g. IP manufacturing
records
Other trial-related
records that “permit
evaluation of the conduct
of the trial and quality of
data produced”
Minimum list of essential
documents from ICH
The Trial
Master File
e.g. safety monitoring, EDC, data
mgmt, biostats
• ICH GCP Section 8 identifies “The minimum list of essential documents....”
• Does not provide the comprehensive contents required for TMF inspection
e.g. protocol, ICF, MVR,
drug shipment
e.g. incorporation papers

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TMF Reference Model background
Industry-wide effort (via DIA EDM SIAC) on content required for TMF inspection
• More than 150 companies and 250 individuals
• No agency endorsement or requirement, reviewed with positive feedback
• Offers standard content, structure, naming, definitions and metadata
Thoroughly detailed and fairly complex
• By the numbers: 244 artifact rows, 30 columns
• Organized by Zones and Sections
• Covers trial files for biopharm and device sponsors, sites, IIS
• Details include ICH, EDM, trial process, file level, more….
Alternate names Definition / Purpose
Core or
Recommen
ded
ICH
Code EDM RM
Unique ID
Number
Sponsor
Document
Investigator
Document
02
Central Trial
Documents 02.01
Trial
Documents 02.01.02 Protocol
Clinical Investigation
Plan (Devices)
To describe the objective(s), design,
methodology, statistical considerations,
and organization of a trial..... Core
1.4.4
8.2.2
Full
Protocol 032 X XG
TMF Zone Section Artifact name

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TMF Success Strategies - Information Architecture
Robust TMF information architecture base is mission critical
• Delivers many faceted dividends, and is foundational for both paper and
electronic TMF inspection readiness
• Generates “do it better” ideation, comprehension and enthusiasm
Robust TMF information architecture base is hard work
• Invest the time nailing the content, classifications, metadata
• Include and align with all content creators, content stewards, trial and
senior management
Robust TMF information architecture is worth it
• Ensure your TMF is accurate, robust + inspection ready
• Mitigate the TMF effort in M&A, partnerships, outsourcing
• Enable team focus on trial completion, not wheel reinvention or post-study
scramble
OK! I’m ready….now what?

8. Paragon Solutions, Inc. Proprietary and Confidential
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Survey the landscape
Set the table
• Sell project to sr. mgmt, secure one exec sponsor
• Gather the team – represent all roles involved in trial processes
Harvest the materials
• Collect all SOPs and instructions on trial processes
Identify your company’s TMF issues
• Artifact handoff confusion
• Two or more “original” filing locations
• Issues with TMF audits / inspections
• Record retention clarity
Drug Information Association www.diahome.org
Know thyself!
Survey the
landscape

9. Paragon Solutions, Inc. Proprietary and Confidential
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Differentiate the issues
Can do!
• Artifact source
• Content definition
• Filing responsibility
• Timing requirements
• SOP identification
• Other metadata
• Avoid black holes
– Turf wars
– Creationism
– Legal holds
– System revamps
– Other improvement initiatives
Regions of space
from which nothing,
not even light, can escape
Survey the
landscape
Differentiate
the Issues

10. Paragon Solutions, Inc. Proprietary and Confidential
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Level the Playing Field
Get the buy-in
• What are we doing and why?
Don’t assume TMF comprehension or standard vocabulary
• Standards and definitions – template, final, index, artifact
• TMF 101s for all participants
Respect the learning curve
• Ramp up time for model comprehension and ingestion
WIIFM???
Survey the
landscape
Differentiate
the Issues
Level the
Playing Field

11. Paragon Solutions, Inc. Proprietary and Confidential
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Prepare the Tools
Copy TMF RM for Master TMF Index, adjust columns
• Rename headers and add additional columns
• Lock unique number column for mapping
Create work plan, meeting schedule and deliverables
Prepare all participants for rigorous discussion
Agree on scope and conflict resolution
• Content lifecycle: final document filing, not creation or destruction
• Predetermine where the buck stops
• Process for resolving disagreements
Survey the
landscape
Differentiate
the Issues
Level the
Playing Field
Prepare the
Tools

12. Paragon Solutions, Inc. Proprietary and Confidential
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Get the Job Done
Be vigilant for squirrels and black holes
• Structure / buckets / containers do not matter, don’t let it break the stride
• Agree to and use the parking lot (outdated SOPs, immature/broken
processes)
Keep inspection readiness at forefront
• Laser focus: is it required for a future inspection? Do our SOPs say we
produce it? If requested, who would be responsible and where would they
have it?
• Make it personal: “If you’re in the room with an inspector…”
Survey the
landscape
Differentiate
the Issues
Level the
Playing Field
Prepare the
Tools
Get the Job
Done

13. Paragon Solutions, Inc. Proprietary and Confidential
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Get the Job Done
Work through the model: “trust but verify”
• Complete the index grid, row by row
• Quick wins, reiterations, subgroups for problem areas
• Carefully consider recommended, GCP codes and your regional regs.
• Keep sr. mgmt. and executive sponsor apprised of progress / problems / success
Apply the new standard
• New TMFs: Update TMF SOPs, WI, manual, apply to electronic systems
• Current TMFs: Risk-based approach - inspection, duration
• Hold mapping sessions with partners/vendors
Maintain new TMF index
• Safeguard the output for reuse and future considerations, partnerships and M&A
C-E-L-E-B-R-A-T-E, spread the word and thank all participants
Survey the
landscape
Differentiate
the Issues
Level the
Playing Field
Prepare the
Tools
Get the Job
Done

14. Paragon Solutions, Inc. Proprietary and Confidential
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Polling Question #2
2. What is the status of your organization’s eTMF?
a) We currently use eTMF
b) Actively building / implementing
c) Evaluating
d) Not considering
e) Unknown / not applicable

15. Paragon Solutions, Inc. Proprietary and Confidential
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Core/ Recommended, Signatures, Versioning
Definition / Purpose
Core /
Recommended
Trial
Oversight 01.01.08 Monitoring Plan
To describe how monitoring will be implemented during
the trial, including strategy for source data verification. Core
Trial
Oversight 01.01.09 Medical Monitoring Plan
To describe how medical surveillance of trial subjects
will be assured during the trial. Core
Trial
Oversight 01.01.10 Publication Policy
To describe the policy for publishing the trial results if
publication policy is not captured within the protocol. Recommended
Section Artifact name
Needed for
Country or Site
Startup
Signature or
Electronic
Workflow?
Version
Control?
Filter
Optional

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Document Lifecycle Management
Where to
File?
Template
Study
Specific
Country
Specific
Site
Specific
May expand
the list of core
documents
required at a
milestone

17. Paragon Solutions, Inc. Proprietary and Confidential
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Specific Artifact Considerations
Artifact Phase II-IV Exploratory
IVRS-IWRS Training Documentation Yes No
Operational Procedure Manual Yes No
Quality Plan Yes No
Adjudication Committee Document Yes No
Other Considerations and Examples:
• Therapeutic Area Specific – Oncology Database Lock
• Patient Population - Pediatric Informed Consent Form
• Country Specific – Investigator Medical License
• Controlled Substance Tracking – DEA Form 222
• Company specific – Translation Explanation or Approval
• Vendor Specific – Central Lab Normals
• Enhanced Access Control – Contracts

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Suggested Additions to the TMF Reference Model
• Accountability – chain of custody, audit trail
• File locations – central, local, site
• SOP and Template relationships
• Documents requiring translation and relationship of
translated document to the original
• Which date(s) and formats are required / optional /
system generated

19. Paragon Solutions, Inc. Proprietary and Confidential
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Metadata Madness
Metadata Functions: Creation Considerations:
• Search - User Entry
• Filter - Look up fields
• Sort - System generated / auto-fill
• Labels - CTMS Interface
• Reports - Mandatory / Optional
Examples:
• Study and Protocol Data
• Country and Site Data
• Site Personnel Names and Roles – CVs, FDA Form 1572,
• Text to differentiate the same artifact received multiple times – Protocol Signature Pages
• Creation, Approval and Revision Dates
• Vendor Name and Role
• IRB/EC Name
• Lab Name
• Financial Disclosure Form

20. Paragon Solutions, Inc. Proprietary and Confidential
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Michael Agard, Senior Consultant, Paragon Solutions
magard@consultparagon.com
Fran Ross, Principal Consultant, Paragon Solutions
fross@consultparagon.com
Jeff Crawford, Director, Life Sciences, Paragon Solutions
jcrawford@consultparagon.com
TMF Reference Model links
Follow the blog - http://tmfrefmodel.blogspot.com/
LinkedIn discussion group - “TMF Reference Model”
Get V2.0 of the Model / In-depth Overview / Join the Team:
www.diahome.org/en/News-and-Publications/Publications-and-Research/EDM-Corner.aspx
Questions and More Information