The document provides an overview of a webinar on TMF fundamentals presented by Montrium. The webinar agenda includes an introduction to Montrium, defining what a TMF is, common TMF challenges and how to alleviate them, leveraging regulations to ensure success, using basic metrics to better manage the TMF, and advantages of an electronic TMF. Key topics discussed include the TMF reference model, roles and responsibilities, tips for managing the TMF including clear governance and technology, and how an eTMF can help with collaboration, oversight, inspection readiness and metrics.

2. TMF Fundamentals
An Introduction to Better Trial
Master File Management
eTMF Bootcamp Webinar Series
Thursday, 21 March 2019
2

3. 3
Agenda
LIVE WEBINAR
• About Montrium
• What is a TMF?
• TMF Challenges and How to Alleviate Them
• How to Use Regulations to Ensure Success
• Basic Metrics and How to Leverage them to Better Manage
Your TMF
• Advantages of an eTMF

4. House Keeping
4A B O U T T H E C O M P A N Y

5. 5
House
Keeping
L I V E W E B I N A R
• This webinar is being recorded and
will be made available after this
session
• Feel free to use the chatbox to
submit your questions at anytime
• Q&A will take place at the end of
the webinar

6. 6
Meet Your
Speakers
.
Mayeesha
Rahim—
Product Specialist,
Montrium
Katherine
Cianciarelli—
Product Owner,
Montrium

7. • Founded in 2005
• Working Exclusively in the Life Sciences
• Headquartered in Montreal, Canada
• EU HQ in Belgium
• Clients in North America, Europe & Asia Pacific
• Leading Content Management Platform
• Over 10,000 Users in 20+ Countries
• Experienced Professional Services Group
7
About
Montrium
Connecting People,
Processes & Technology
A B O U T T H E C O M P A N Y

8. 8
Electronic Content
Management & Business
Intelligence tool for Clinical
Trials
C O N N E C T M A N A G E M E N T P L A T F O R M F O R T H E L I F E S C I E N C E S
Regulatory Document
Management & Submission
Planning tool for Drugs and
Devices
Integrated and Data Driven
Quality Management tool

9. What is a TMF?
S E C T I O N # 1
9A B O U T T H E C O M P A N Y
P R E S E N T E D B Y K A T H E R I N E C I A N C I A R E L L I

10. The Trial Master File (TMF) or its
modern form, the Electronic Trial
Master File (eTMF), is a collection of
essential documents that are
collected during the course of a
clinical trial.
This group of documents allows the
conduct of a clinical trial to be
reconstructed and evaluated at any
point in time and provides a story of
how the trial was managed and
carried out. This collection of
documents has to be updated
regularly and the TMF completeness
evaluated continuously.
10
What is a
TMF?

11. The TMF Reference Model provides
standardized taxonomy and metadata
and outlines a reference definition of
TMF content using standard
nomenclature.
11
TMF Reference
Model

12. T M F R E F E R E N C E M O D E L

13. Are you currently using the DIA
TMF Reference Model?
a) Yes, version 3.0
b) Yes, version 3.1
c) A hybrid
d) no
POLL

14. TMF Challenges
and How To Alleviate Them
S E C T I O N # 2
14A B O U T T H E C O M P A N Y
P R E S E N T E D B Y M A Y E E S H A R A H I M

15. • Culture of reactive TMF
management
• Lack of well defined roles and
responsibilities
• Lack of contemporaneous
filing
• Outsourcing and lack of
oversight
• Unclear TMF Scope
15A B O U T T H E C O M P A N Y
TMF
Management:
What needs to
change

16. 16
What does
reactive TMF
management
looks like?
Graph created by: Andy Fisher

17. Everyone thinks the TMF only
belongs to the clinical team but in
reality, there are documents from
many different cross functional
teams that are all TMF relevant.
As such, it is important to
define who is responsible
for adding the artifacts to
the TMF and ensuring
the document content, metadata,
and indexing are complete and
accurate.
17
Roles and
Responsibility

18. RACI Charts can be used to establish the
expectations of who will complete tasks
associated to TMF Management
R = RESPONSIBLE
A = ACCOUNTABLE
C = CONSULT
I = INFORM
18
RACI CHART
what is it?
A B O U T T H E C O M P A N Y

19. 19
Example of
RACI chart
DirectorofClinical
CRA
ProjectManager
CTA
DataManager
PharmacovigilanceSpecialist
Statistician
Authoring Documents C,I R A I R R R
Filing and Indexing I R A R A A A
QC I R A R R R R
Maintaining Quality, Timeliness and
Completeness A I A I I I I

20. Do you know who is responsible for
the day-to-day TMF management in
your organization for a particular
study?
a) Yes, it’s clearly defined.
b) No, I’m not really sure.
c) I’m not currently working in an organization
responsible for managing TMF.
20
POLL

21. 1. Clear governance and oversight
2. Defined TMF Filing Structure
3. Centralizing content through technology
4. Contemporaneous use of basic metrics
5. Effective QC
21
Tips for
managing
your TMF

22. Leveraging Regulation to
Ensure Success
P R E S E N T E D B Y K A T H E R I N E C I A N C I A R E L L I
S E C T I O N # 3

23. FDA CGMP
Guideline on GCP compliance in
relation to trial master file (paper
and/or electronic) for content,
management, archiving, audit and
inspection of clinical trials
Integrated addendum to
ICH E6(R1): Guideline for
Good Clinical Practice
E6(R2) (November
2016)
MHRA GxP Data Integrity
Guidance and Definitions,
Revision 1 (March 2018)
FDA Data Integrity and
Compliance with CGMP
(April 2016)
FDA Use of Electronic Records and
Electronic Signatures in Clinical
Investigations Under 21 CFR Part 11
Questions & Answers’
(June 2017)
21 CFR PART 11
MHRA GxP Data
Integrity
Definitions
ICH
E6 (R2)
EMA
15975/2018
The Regulatory Landscape

24. A trial master file inspection
refers to “the act by a regulatory
authority, in conducting an
official review of documents,
facilities, records, and any other
resources that are deemed by
the authority to be related to the
clinical trial and that may be
located at the site of the trial,
sponsor’s and/or CRO’s
facilities, and other
establishments deemed
appropriate by the regulatory
authority” (ICH GCP Sec 1.29).
24
What is a TMF
inspection?

25. Inspection readiness is a quality
objective - the objective being to
operate at a level that is always
ready for inspection, without
requiring much preparation in the
days or hours leading up to the
inspection.
Inspection readiness starts by
understanding the regulatory
expectations for your TMF.
25
What is
inspection
readiness?

26. What are the
regulators
looking for?
(in inspections)
1. To receive some form of access to the
TMF, whether direct or assisted
2. To be able to review TMF related metrics
that tell the story of how the study has
been conducted and how the TMF has
been managed
3. To easily access TMF relevant content
that is not primarily stored in the TMF
4. That the sponsor ensures oversight of any
outsourced activities including TMF
management

27. Basic metrics and how to
leverage them to better
manage your TMF
S E C T I O N # 4
27A B O U T T H E C O M P A N Y
P R E S E N T E D B Y M A Y E E S H A R A H I M

28. 28
Completeness
The TMF is considered to be complete when all of the
documentation collected over the course of a clinical trial are
available in the TMF in an organized and auditable way that
ensures that the trial can be reconstructed.

29. 29
Completeness
Practical Considerations
- - Start with the easiest attribute – milestones
- - Build eTMF plans based on specific study designs
- - Identify study events which would require artifacts e. protocol amendment, safety
case
- - Evaluate data needs to identify and calculate completeness of artifacts contained
outside of the primary system

30. 30
Timeliness EMA:
“Article 57 states “the clinical trial master file shall at
all times contain the essential documents relating to
that clinical trial.” The requirement “at all times”
means that the TMF should be updated, and
completed in a timely manner.”
“[…] it is important, therefore, to keep the TMF up to
date, with documents placed in the TMF in a timely
manner as this greatly assists the successful
management of a trial by the investigator and
sponsor (or party to whom the sponsor has delegated
its duties).”
- ICH E6:
- “Filing essential documents at the
investigator/institution and sponsor sites in a timely
manner can greatly assist in the successful
management of a trial by the investigator, sponsor and
monitor.”

31. 31
Timeliness
Practical Consideration
s
• Establish methods for measuring
timeliness and standards around
dates
• Consider a process to define when
TMF artifacts need to be in a TMF
• Establish a mechanism for
detecting missing artifacts
• Most documents can be tied to a
milestone e.g. Site Selected -> Site
Initiated
• Compliance with protocol
timelines, study plans
established at trial start
- Workflows

32. 32
Quality
- The Trial Master File Reference
Model Quality Group’s (TMF
RM QG) Recommendations for
TMF quality review specifies a
two step process for the review
of the tmf, including
firstly quality control of each of
the individual documents as
well as the entire TMF.

33. 33
Quality
Practical
Considerations
- Define a plan for risk-based TMF
review, consider:
• Study design and complexity
• Number of vendors
• Number of systems used containing TMF records
• Assigning risk scores to document types based
on process risk and other factors
- Think about how you can better
organize information to better tell the
story of what happened and leverage
this information to assess risk

34. Which metric do you find most difficult
to track?
a) Missing documents
b) Completeness
c) Expired Documents
d) Quality
e) Timeliness
34
POLL

35. How an eTMF can help
TMF Management
S E C T I O N # 5
35A B O U T T H E C O M P A N Y
P R E S E N T E D B Y K A T H E R I N E C I A N C I A R E L L I

36. How are you currently managing
your Trial Master File(s)?
a) Paper
b) File share
c) Hybrid - paper & file share
d) eTMF
e) I’m not actively involved in managing a TMF
POLL

37. eTMF systems provide users with
the ability to extract key business
intelligence from documents,
which allow for better long term
decision making.
Real time
metrics and
reporting

38. Collaboration
on
documents
In an eTMF, collaboration can
happen in parallel, documents are
transferred instantaneously, and all
actions can be tracked. By
leveraging cloud technology,
changes and reviews can occur
simultaneously. Signatures can be
performed both electronically and
CRF Part 11/Annex 11 compliantly.
This slims the trial process in a
huge way, further driving time and
operational efficiencies.

39. Increased
oversight
Working in an eTMF allows users to
have oversight on the documents that
are authored and uploaded, the
metadata associated to these
documents and ownership of each
document. There is also traceability
which allows sponsors to demonstrate
oversight when outsourcing to a CRO.

40. Inspection
Readiness
When you have everything
electronically managed in an eTMF,
it's easier to evaluate whether your
eTMF is complete and ready for an
audit or inspection. The eTMF system
allows you to clearly see what you'll be
presenting to an inspector, which
documents have gone through formal
quality control, and whether your
documents are of sufficient quality.

41. 41
• Facilitate exchange of clinical trial
information to all stakeholders
• Accurately track the progress of
TMF completeness
• Quickly comply with regulatory
requirements, audits and
inspections
A Complete eTMF
Platform Engineered for
Growth Organizations

42. Are you interested in receiving
more information about eTMF
Connect?
1) Yes, could be useful
2) No, not interested
42
POLL
A B O U T T H E C O M P A N Y

43. QUESTIONS?
43A B O U T T H E C O M P A N Y

44. INFO@MONTRIUM.COM
Thank You!