The document discusses the importance of Trial Master File (TMF) inspection readiness, outlining the need for continuous preparedness to meet Good Clinical Practice (GCP) standards and avoid negative consequences like failed inspections and increased costs. It highlights what inspectors expect from TMF management, including compliance, organization, and ease of access, while providing guidelines on how organizations can establish effective TMF systems. The document emphasizes that technology alone cannot ensure inspection readiness, but proper infrastructure, governance, and metric management can significantly enhance overall readiness.

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Let the Potential of Your Business Emerge
Powering Your TMF for Inspection Readiness
Ensuring complete and accurate records
Chris McSpiritt
MAGI West 2016

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Paragon Solutions, Inc. Proprietary and Confidential
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Topics
• Why inspection readiness?
• What do inspectors expect?
• How can we ensure readiness?

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WHY INSPECTION READINESS?

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Paragon Solutions, Inc. Proprietary and Confidential
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Why TMF Inspection Readiness?
A Trial Master File (TMF) is required for every trial run
to ICH Good Clinical Practice(GCP)standards
TMF Inspection Readiness is the state of continual
preparedness for a health authority GCP inspection,
everywhere, anytime

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Paragon Solutions, Inc. Proprietary and Confidential
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Why do we care?
The implications of not being ready are obvious:
1. Rush to prepare for inspections
1. Not doing regular job
2. Extra costs
2. Unsuccessful inspections
1. Health Authority Findings
2. Fines
3. Response costs
4. Risk to product approval

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WHAT DO INSPECTORS EXPECT?

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High-level Inspector Expectations
Each TMF autonomously proves sponsor and site GCP
compliance and full story of study execution
• Protocol followed
• Data accurate
• Subjects safe
• Decisions made
TMF management complies with both good record
keeping practices (e.g. ALCOA) and all applicable
predicate rules(e.g.Part 11)

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Paragon Solutions, Inc. Proprietary and Confidential
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Demonstration of Control
Holistic Organization
Controls
• Full lifecycle -
creation to archive
• Effective structure
• Controlled access
• Investigator’s file
oversight
• Availability to all
TMF content
Content
Management Rigor
• Content robust
• Version control
• Timely filing
• Subject protected
• Decisions
documented
Process Controls for
Each TMF
• CRO oversight
• Consistency
• Quality assurance
• Location and chain
of custody
• Issue remediation
TMF Inspection enables full reconstruction of the trial

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Paragon Solutions, Inc. Proprietary and Confidential
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Ability to understand/recreate the study
Duration
• eTMF inspection
should not take
longer than
equivalent paper
inspection
• Limited time for
inspector training
(less than 1 hr)
Access
• Arrange for direct
access for
inspectors
• Ensure adequate
equipment and
system
performance
• Facility to print
content at
inspector request
• Location of all
TMF source
systems clear
Ease of Use
• Inspector is able
to self-navigate
• Structure is self
evident
• Supportive
Search/report
functionality
• Able to facilitate
access across
source systems
Visibility
• Facilitate the
presentation of
the documents at
actual size
• Ideally, side-by-
side comparison
(dual screen set-
up), annotation
abilities
(bookmarking) to
facilitate the
review
They want to be able to do it with minimum effort:

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Paragon Solutions, Inc. Proprietary and Confidential
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How do electronic systems fit in?
System Controls
• Security
• Training
• Access
• Audit trial
System Processes
• Validation
• Back up
eTMF Content
Clarity
• Metadata
• Naming
• Scanning
• Locking
• Workflow
approval
System Expectations

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HOW DO WE ENSURE READINESS?

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Paragon Solutions, Inc. Proprietary and Confidential
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The bad news for vendors
The system you use will not make you inspection
ready!
• A TMF/Regulatory Binder can be made inspection
ready using any technology.
However, they can assist you in the journey.

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Paragon Solutions, Inc. Proprietary and Confidential
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Components of readiness prep
Create infrastructure
• TMF Quality
Management System
•High-level, fits all trials
•Governance
•Structure and Processes
•Metrics
•Standard TMF
Architecture
•Standard list for typical
trials
•Leverage industry's TMF
Reference Model
•Make specific – doc
names, definitions, align
to SOPs, identify
responsible roles
•Tools
•Content management
system
•Integration with data
source systems
Prepare for each study
•TMF Plan
•Framework for how that
study’s TMF will be
managed
•Clearly identify
exceptions and/or
additions to process
•TMF Index
•That study’s adaptation
of the organization’s
standard TMF
architecture
•Ensure all source systems
referenced
•Quality Management
•Outline study team’s
responsibilities
Manage the study
•Make sure the TMF
reflects what is happening
•Ensure communication
between study team and
those managing content
•Monitor metrics
•Verify timely collection of
content
•Execute Quality Oversight
activities including
remediation activities
•Maintain evidence of
execution

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Paragon Solutions, Inc. Proprietary and Confidential
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How do metrics fit in?
Per the TMF Reference Model Committee there were three
parameters for metrics:
1. Quality - so that all parties have confidence in the processes and data
2. Timeliness – so that accurate decisions can be made
3. Completeness – so that authorities can inspect the study
Work to incorporate metrics so that you can continuously
improve internal (or service provider) study execution.
Metrics reporting are the key tool to proactively manage
the CRO/Sponsor relationship during study execution.

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Who contributes to readiness
• Study Team is TMF responsible
• All team adheres to SOPs / TMF Manual
• Each TMF has team Owner
• Records Mgmt is TMF supportive
• TMF Q&A, templates, training, archive
• TMF Metrics production
• Clinical Mgmt is TMF accountable
• Mandates behaviors and consequences
• TMF Metrics champions
• Quality Mgmt is TMF transformative
• Take audits from"old news gotchas" to proactive mock
inspections