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

2. 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
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3. Paragon Solutions’ Introduction
Paragon is an enterprise information management
solutions company that helps firms leverage
Corporate Facts information assets to achieve better business
results.
• 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
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4. 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
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5. Why a TMF Reference Model?
• ICH GCP Section 8 identifies “The minimum list of essential documents....”
• Does not provide the comprehensive contents required for TMF inspection
Minimum list of essential The Trial
documents from ICH
e.g. protocol, ICF, MVR, Master File
drug shipment
Other trial-related
records that “permit
evaluation of the conduct Supporting records
of the trial and quality of generally outside TMF
e.g. IP manufacturing
data produced” records
e.g. safety monitoring, EDC, data
mgmt, biostats
Other business records
e.g. incorporation papers

6. 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
Core or
Recommen ICH Unique ID Sponsor Investigator
TMF Zone Section Artifact name Alternate names Definition / Purpose ded Code EDM RM Number Document Document
To describe the objective(s), design,
Central Trial Trial Clinical Investigation methodology, statistical considerations, 1.4.4 Full
02 Documents 02.01 Documents 02.01.02 Protocol Plan (Devices) and organization of a trial..... Core 8.2.2 Protocol 032 X XG
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….
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7. 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?
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8. Survey the landscape
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
Know thyself!
Paragon Solutions, Inc. Proprietary and Confidential
-8- Drug Information Association www.diahome.org

9. Differentiate the issues
Survey the Differentiate
landscape the Issues
Can do! • Avoid black holes
• Artifact source – Turf wars
• Content definition – Creationism
• Filing responsibility – Legal holds
• Timing requirements – System revamps
• SOP identification – Other improvement initiatives
• Other metadata
Regions of space
from which nothing,
not even light, can escape
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10. Level the Playing Field
Survey the Differentiate Level the
landscape the Issues 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???
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11. Prepare the Tools
Survey the Differentiate Level the Prepare the
landscape the Issues Playing Field 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
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12. Get the Job Done
Survey the Differentiate Level the Prepare the Get the Job
landscape the Issues Playing Field Tools 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…”
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13. Get the Job Done
Survey the Differentiate Level the Prepare the Get the Job
landscape the Issues Playing Field Tools 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
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14. 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
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15. Core/ Recommended, Signatures, Versioning
Signature or
Electronic Needed for
Filter Version Country or Site
Workflow? Startup
Control?
Core /
Section Artifact name Definition / Purpose Recommended
Trial To describe how monitoring will be implemented during
Oversight 01.01.08 Monitoring Plan the trial, including strategy for source data verification. Core
Trial To describe how medical surveillance of trial subjects
Oversight 01.01.09 Medical Monitoring Plan will be assured during the trial. Core
Trial To describe the policy for publishing the trial results if
Oversight 01.01.10 Publication Policy publication policy is not captured within the protocol. Recommended
Optional
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16. Document Lifecycle Management
Where to
File?
Country
Template Specific May expand
the list of core
documents
required at a
milestone
Study Site
Specific Specific
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17. 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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18. 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
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19. 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
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20. Questions and More Information
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
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