We will be exploring the best practices for preparing and surviving TMF inspections. We'll start by diving into why inspection readiness should be continuous, and share some key strategies to ensure your team has a successful inspection.

2. Best Practices
for Preparing for
and Surviving a
TMF inspection
2
The eTMF Bootcamp 2.0

3. 3
Agenda
LIVE WEBINAR
• What is a TMF?
• What is an Inspection?
• Why it is important to be inspection ready at all times?
• Creating a Culture of Inspection Readiness
• Inspection Prep Cheatsheet

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
.
Sara
Naushin—
Sales Engineer,
Montrium
Katherine
Cianciarelli—
Product Owner,
Montrium

7. • Founded in 2005
• Working Exclusively in the Life Sciences
• Headquartered in Montreal, Canada
• EU HQ in Brussels
• Clients in North America, Europe & Asia
• Leading Content Management Platform
• Over 8000 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 for Clinical
Trials
C O N N E C T P L A T F O R M
Regulatory Document
Management & Submission
Planning for Drugs and
Devices
Integrated and Data Driven
Quality Management
Solutions for Life Sciences

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 S A R A N A U S H I N

10. The Trial Master File (TMF) or its
modern form, the Electronic Trial
Mater 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. 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

12. What is an Inspection?
S E C T I O N # 2
12A 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 S A R A N A U S H I N

13. 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).
13
What is an
inspection?

14. 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.
14
What is
inspection
readiness?

15. Why is it important to be
inspection-ready at all
times?
S E C T I O N # 3
15A 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 S A R A N A U S H I N

16. 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
(December 2018)
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/INS/GCP/
856758/2018
The Regulatory Landscape

17. 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

18. Creating a Culture of
Inspection Readiness
S E C T I O N # 4
18A 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

19. • Culture of reactive TMF
management
• Lack of well defined roles and
responsibilities
• Lack of contemporaneous
filing
• Outsourcing and lack of
oversight
• Unclear TMF Scope
19A B O U T T H E C O M P A N Y
Why is it
difficult to be
inspection
ready at all
times?

20. 20
What does
reactive TMF
management
looks like?
Graph created by: Andy Fisher

21. The TMF was presented as a paper TMF for inspection.
However, the TMF did not contain all the essential
documents required to enable the reconstruction of
trial events and demonstrate compliance with the
regulations and the organization's own quality system.
Several essential documents were retained within
different electronic systems which were not defined to
be part of the TMF and to which inspectors were not
provided direct access (even with a guide user).
Where the TMF maintenance had been contracted out
to a third-party contractor, there was limited
information available in the organization's own files to
demonstrate effective oversight of clinical trial
activities to fulfil its obligations as a sponsor.
21
Critical
Findings
reported
by the
MHRA
For Sponsors
MHRA – GCP Inspection Metrics Report
1
2
3

22. The TMF presented for inspection did not meet the
requirements to be the basis of the inspection. The
inspection was extended as it required the inspectors to
return after 4 months.
It was not clearly defined in the agreements with trial
sponsors the scope of the TMF that was required to be
held by the CRO.
The eTMF lacked essential functionality.
The TMFs has not been maintained to a sufficient
standard and issues were found with the accuracy and
reliability of the TMFs.
22
Critical
Findings
reported
by the
MHRA
For CROs
MHRA – GCP Inspection Metrics Report
1
2
3
4

23. 1. Clear governance and
oversight
2. Effective QC
3. Mock inspections
4. Direct and facilitated
access to electronic
systems holding TMF
content
5. TMF Traceability
23
Readiness
Culture
Musts

24. Clear
governance
and oversight
1) What is the scope of the TMF? Has the TMF plan been
established?
2) Is the TMF managed by an in-house team or third party?
As a sponsor who has outsourced TMF management:
1) Were requirements for TMF management clear in the
agreement or scope of work?
2) Have metrics/KPIs been defined? E.g. late documents,
rejected documents, QC findings
3) Do you have access to the TMF?
4) Do you have regular planned TMF inspections/audits?
As the team that has been delegated the responsibility of
maintaining the TMF:
1) Is the team cross-functional i.e. are all functional roles
(statistics, PV, data management) aware of their contribution
to the TMF?
2) Have roles and responsibilities been defined within the team?
3) Do job descriptions include responsibilities related to TMF
management?
4) Do they have the necessary practical training on TMF
structure and filing system as well as on systems supporting
TMF management?
Questions to consider…
Determine
responsibility and
accountability

25. 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.
25
POLL

26. Effective
QC 1) What is the scope of QC?
2) Has a risk-based approach been
considered?
3) Who will be performing QC?
4) How often will QC be conducted?
5) Have acceptance and rejection criteria
been established?
6) Are there necessary tools and processes
in place to document and facilitate QC?
7) What is the process for documenting
findings and timely implementation of
corrective actions?
Questions to consider…
Demonstrate quality
in a complex system

27. Mock
Inspections • Helps to decrease inspection anxiety
• Decreases the risk of reactive behaviour
• Increases the quality of your system
• Identifies training gaps
• For CROs, build sponsor confidence
• Helps to put people in the picture
Why are mock inspections helpful in building a
culture of inspection readiness?
Develop confidence
through practice

28. Direct and
facilitated
access to
electronic
systems holding
TMF content
1) Have all systems which contain TMF
content been identified in the TMF Plan?
2) Is there a plan for accessing the systems in
the case of an inspection?
3) Will an inspector have direct access or
guided access?
4) Is there a short guide or training that will be
planned and provided to the inspector and
has this been included as part of the
inspection agenda?
5) If direct, is there an interface for an
inspector view provided by your vendor?
6) If guided, who will be responsible for guiding
the inspector?
Provide the necessary tools
to facilitate the inspection
Questions to consider…

29. TMF
Traceability 1) Is the audit trail/activity log defined?
2) What is being logged in the audit trail?
3) Is the audit trail complete enough to
demonstrate traceability of activities in
the eTMF?
4) Has the audit trail been periodically
reviewed?
5) Do you have access to export the audit
trail?
6) Can you demonstrate timeliness? And
have you defined it?
Questions to consider…
Demonstrate
traceability and
timeliness

30. Inspection Prep
Cheatsheet
S E C T I O N # 5
30A 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

31. Pre-
inspection…
• Ask the inspector for an agenda
• Notify your vendors of an upcoming inspection
• Book conference room with adequate space and
equipment for the duration of the inspection
• Send preliminary information to allow the
inspector to become familiar with your TMF
model and any systems used in managing TMF
content
• Identify all TMF documentation and determine
how it will be made available to the inspectors
• Schedule a refresher on TMF processes with the
team who will support the inspection if needed
• Arrange for direct access to your eTMF and
where possible, any other system holding TMF
relevant content that may be referenced
• Inspector accounts should be read-only but should
have access all features necessary for inspection
(version history, access to final records)
• Include short user guide/training
• Be prepared to demonstrate the validated state
of all systems used in the study

32. During an
inspection… • Present your TMF management procedure
and plan
• Provide a listing of electronic systems
containing TMF relevant content
• Provide a short training on the systems which
the inspector will need to access either
guided or direct
• Ensure that relevant team members are
available for questions

33. Post-
inspection…
• Ask the inspector for a brief summary or closing
meeting to go over any major findings or
observations
• Ask the inspector when to expect the inspection
report
• Upon receiving the inspection report, work with the
relevant team members to respond to findings
• Propose and implement corrective and preventive
actions (CAPAs)
• Verify effectiveness of CAPAs

34. If an inspector walked in today,
would they be able to reconstruct the
trial using the documents and
metadata in your eTMF?
a) Yes, we are inspection ready!
b) Maybe, for the most part…
c) Um… can we ask the inspector to come back
in 3 months?
d) I’m not actively involved in managing a TMF
34
POLL

35. 35
It’s not too late!

36. 1. Develop a comprehensive TMF
Plan
2. Get help if you need it
3. Evaluate the tools used for
managing your TMF
4. Consider performing a mock
inspection with your team
36
Take one
Right Step at
a time…

37. 37
• 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

38. Are you interested in receiving
more information about eTMF
Connect?
1) Yes, could be useful
2) No, not interested
38
POLL
A B O U T T H E C O M P A N Y

39. QUESTIONS?
39A B O U T T H E C O M P A N Y

40. INFO@MONTRIUM.COM
Thank You!