Best Practices for Achieving TMF Quality

BEST PRACTICES FOR ACHIEVING TMF QUALITY

• Utilizing the TMF Reference Model
• Harnessing the power of an eTMF to drive quality and ensure inspection readiness
• Strategies for successfully implementing an eTMF

TRIAL MASTER FILE

The collection of documentation that allows the conduct of the clinical trial, the integrity of the trial data and the compliance of the trial with GCP to be evaluated...

...the TMF being a stand-alone set of documentation that does not require additional explanation from the associated sponsor or site staff.

Article 16 of Directive 2005/28/EC

TMF REFERENCE MODEL

• Originated in 2009 as a single unified interpretation of regulations and practices across the industry
• Provides a standardized structure for organizing the TMF
• Comprised of 11 different zones that are made up of subsections and artifacts with content at the trial, country, and site level

11 ZONES

✓ Trial Management

✓ Central Trial Documents

✓ Regulatory

✓ IRB/IEC and other Approvals

✓ Site Management

✓ IP and Trial Supplies

✓ Safety Reporting

✓ Centralized Testing

✓ Third Parties

✓ Data Management

✓ Statistics

VERSION 3

• Released after DIA meeting in June
• Some revisions to Version 2 structure with minor content revisions
• Addition of sub-artifacts
• Application of interoperability

UTILIZING THE TMF RM WITHIN YOUR ORGANIZATION

• Using the RM to establish organizational core content - often referred to as "Content List"
• Review each artifact to determine the following
  • Terminology is consistent
  • Artifact is relevant
  • Identify metadata
• Establish a study specific map
  • Assign content owner
  • Identity location - during study and at archive

eTMF AS A BUSINESS TOOL

• eTMF moves content from the filing cabinet to the electronic environment
• TMF content held in an electronic environment must be 21 CFR, Part 11 compliant
• An eTMF can be a very powerful business tool
• TMF Quality
  • Completeness
  • Timeliness
  • Record Quality
• Time stamped records
• Remote review of the record in real-time
• Metrics

USING THE eTMF TO ASSESS TRIAL QUALITY

• Metrics Reporting
  • Completeness Reports
  • Quality through metadata
  • Timeliness
• Specific artifact review
  • Monitoring Reports
  • Investigator File Review

eTMF AS A BUSINESS TOOL

• CRO - oversight of alignment of study with study plans
• Sponsor - oversight that CRO activities are in alignment with the study plans
• Poor quality TMF raises concerns of the overall study quality

INSPECTION READINESS

• eTMF alone is not enough
• Quality Control of eTMF is critical to ensuring inspection readiness
  • Using the TMF map as a tool in evaluating TMF completeness

CONSIDERATIONS WHEN IMPLEMENTING AN eTMF

• TMF Structure - Standard Indexing
• Metadata to be tracked
  • System dependent
  • Searchability
  • Consider information that will enhance business operations
• Establish conventions
• Organization wide implications
  • Functional area needs
  • Impact on processes beyond TMF content
• Business partner implications

CONSIDERATIONS TO IMPLEMENTING AN eTMF

• Convincing internal business units that they contribute TMF content
• Business partners that have not adopted the TMF RM
• Content held in different locations - secure vs non-secure solutions

MANAGING EXISTING TMF CONTENT

• Document plan for converting from paper to electronic environment - include QC process
• Integrating paper content into the eTMF environment
• Integrating electronic content into the eTMF environment
• Document what was done, by whom, and results of QC check
• Establishing the Authoritative Source

ESTABLISHING PROCESS

eTMF must be compliant with 21 CFR, Part 11

STANDARD PROCESS

• Maintaining Standard Indexing
• Study Set-up
• Quality Control Activities
• TMF Plan
• Maintaining System Control of the TMF
• TMF Archiving
• Procedural documents
• Supporting forms
• May go through a few iterations until it works for your organization.

eTMF implementation is an opportunity for process improvement.

Balance this with an implementation plan.

ENSURING eTMF QUALITY

• TMF Plan
  • Includes plan for ensuring quality
• Regular quality review
  • Start-up
  • Risk based
  • Quarterly on-going review
• Document review

AT RISK CONTENT

• Amendments (country-specific versions, translations)
• ICFs (country, local, translations, QC checklist)
• Ethics and regulatory submissions (translations)
• Monitoring reports (confirmation letters, reports, follow-up letters, sponsor review)

KEYS TO TMF QUALITY

• Standard indexing
• Standard process
• Using the TMF to drive study quality
• TMF Oversight
  • Ongoing QC for completeness, timeliness, document quality
  • Sponsor Review

DWD & ASSOCIATES

• Quality Management Systems
• TMF Management
• Site Management with focus in Phase I/Early Development
• Sponsor Services

TRANSPERFECT

• 20+ Years in Global Clinical R&D:
  • Translation & Language Service in 175+ languages
  • eTMF Technology & TMF Services
  • Part 11 Compliant eClinical Suite
  • Global Call Center Services