Review of essential documents (TMF BABE).

Prepared By:
Piyush V. Wagh
Senior Executive
Quality Assurance Department
Date: 05th Oct 18
Ref: Drug Master File & Dossiers 1

REVIEW OF ESSENTIAL DOCUMENTS (TMF-BABE)
Introduction
 The complexity of a clinical research trial involves keeping and storing
multiple essential documents that are necessary for a successful trial
and quality results.
 Definition: Essential Documents are those documents which
individually and collectively permit evaluation of the conduct of a
trial and the quality of the data produced. (ICH-E6R2-8.1)
 The term ‘’essential documents’’ refers to the documents which,
according to the ICH-GCP Guidelines, serve to evaluate the trial
conducted, data quality and integrity.
 Maintaining and storing these essential regulatory documents is an
important practice in clinical research.
 The proper filing and organization of these documents can greatly
improve a clinical trial management
2Information adopted from “Best practices for maintaining and storing essential documents in clinical research “ ppt- SlideShare

Essential documents grouped in three sections
1. Before the clinical phase of the trial
commences
2. During the clinical conduct of the trial
3. After completion or termination of the
trial.
3

Before the clinical phase of the trial commences
4
Before
trial
INVESTIGATOR
’S BROCHURE
Protocol/
Amendment/
Erratum
Information
to subject’s
(ICF, Advert.)
Financial
aspects of
trial
(Sponsor
Agreement) INSURANCE
STATEMENT
IEC/ IRB
related
documents
(minutes of
meeting)
IEC
Composition

Before the clinical phase of the trial commences (Conti….)
5
Before
trial
Regulatory
authorization/
approval for
trial
CV for
investigator /
sub-
investigator
Normal value
ranges of test
performed /
technical
Accreditation
to Path lab
Sample label
attached to
IP’s
Procedure of
handling of
IP’s (if not
included in
protocol)
Shipping
records of
IP’s

Before the clinical phase of the trial commences (Conti….)
6
Before
trial
COA of IP’s
Decoding
procedure –
blinding
study
Shipping
records of
IP’s
Trial initiation
and
monitoring
report
Master
Randomization
Copy

During the clinical trial
7
During
Trial
Updated IB
Amendment ,
addendum,
erratum to
protocol/ ICF
IEC approval of
amendment,
addendum, erratum
Regulatory
approval to
amendment,
Addendum
CV for new investigator,
updated CV for existing
investigator
Updated range of
normal value-
Pathological lab
Any other
documents related
IP’s, Shipping
records

During the clinical trial (Conti….)
8
During
Trial
COA for new
batch of IP’s
Monitoring visit log
Findings and
responses
Communication with sponsor
other than site visit-
Approval and intimation of
deviation
Signed
informed
consent form Source documents
Signed and
completed CRF
DOCUMENTATION
OF CRF
CORRECTIONS

9
During
Trial
Any notification
for SAE with
sponsor / IEC
Notification by the
sponsor about updated
safety information
INTERIM OR ANNUAL RE
PORTS TO
IRB/IEC AND AUTHORITY
(IES)
SUBJECT
SCREENING
records SUBJECT IDENTIFICATI
ON CODE LIST
SUBJECT
ENROLMENT
Record
IP’s Accountability
on site

10
During
Trial
Document signatures
and initials of all
persons
authorized to make
entries and/or
corrections on
CRFs – Delegation
Form
RECORD OF RETAINED B
ODY FLUIDS/
TISSUE SAMPLES (IF ANY)

After the clinical phase
11
After
trial
Final
accountability of
IP’s
DOCUMENTATION OF
IP’s DESTRUCTION
Complete identification
code list- Original ID card
with photocopy-
Enrollment Log.
AUDIT CERTI.
(QA
Authentication) FINAL TR IAL CLOSE-OUT
MONITORING REPORT
Decoding
Documentation-
Blinding study
Final report to
IRB/IEC about
completion of trial
And
CSR

1. Checklist for Essential Documents.
12
• To check the checklist and it’s completeness
with signed.
• To read every point and recorded entry
whether document compiled or not

2. Project Initiation Form
13
• Check the initiation form version number.
• To check the initiation of trial date and
appointment of study director. –Must be
before initiation of draft protocol

2. Project Initiation Form
14
• Check the initiation form version number.
• To check the initiation of trial date and appointment
of study director. –Must be before initiation of draft
protocol.
• Delegation of study team- Investigator delegation - Must
be before initiation of draft protocol.

3. Sponsor Correspondence
15
• Check the all the communication regarding the trial.
• Communication means –
• Draft protocol, final protocol, amendment/ addendum to protocol,
ICF, erratum
• sponsor signed page communication,
• study schedule, appointment of monitor for study,
• clinical study update,
• any approval for deviation and intimation for deviation, decoding
of list, any protocol violation .
• Clinical Study Report- Finalization of CSR.

4. Product Monograph
16
• Check the updated monograph- Check the
revision date from protocol reference section.
• Check all the pages and it’s completeness.
• Reference molecule name must be reflected.
• Add the all the reference used during the
protocol preparation.

5. Approved Protocol
17
• Check all the pages of original/ approved
protocol.
• Check Stamp of EC on every page.

Sr. 6,7 and 8
6. Sample ICF for Screening (English, Hindi & Marathi) –
Updated ICF, ICF used during the study
7. Informed Consent Form for Study (English, Hindi & Marathi)
- Original approved ICF
- Check completeness of document
8. Translation Certificate
- Translation certificate for all ICF- Screening, Registration, Study ICF
- Check the version number and Certificate version number should be
same
- Check the date of vernacular ICF with the translation certificate.
18

Sr. 9,10 and 11
9. Sample Case Report Form
-Draft CRF with reviewer signed pages
10. Insurance Statement
- Updated/ Valid insurance copy
- If study period start on 30th Dec 17 then both copy of insurance
must be compiled in the TMF
11. IEC Composition
-Updated Copy of composition
-Check the IEC/ IRB composition from minutes of meeting.
19

Sr. 12,13,14,15
12. IEC Correspondence (Communication)
-Communication regarding the approval of research proposal. (Application letter,
acknowledgement copy of received documents, erratum submission, amendment/
addendum submission, CSU submission mail, summary report submission)
- any form of communication (written and oral)
13. Minutes of Meeting
- Date and time of meeting
- Members present during the meeting
- Favorable opinion/ vote by the members
14. IEC Approval Letter
-Protocol (version number and title) approval
- Approval signed and date
15. Indemnity (Guarantee from investigator)
-Any investigator appointed – indemnity required
- Management change- New indemnity required
20

Sr. 16,17,18
16. Curriculum Vitae (Principal Investigator, Clinical Investigators &
Bioanalyst)
- Updated CV from earlier to recent – Time period from check-in to report
preparation
17. Letter to Contact Hospital
- Letter information about the check-in and check-out schedule date
- If schedule change- letter change
- Submission dead line - Before check-in
18. Shipping Records of IP’s
- Every Shipping records – Check the received date from the drug
store logbook and confirm the shipping records.
- Check the covering letter of IP’s 21

Sr. 19 and 20
19. Certificate of Analysis
- Check the COA with name of IP’s and batch number and expiry date
- Cross-verify the details from Drug store logbook, dispensing records
and IP’s box labels
20. Sample Labels attached to IP container
- Sample Box Label attached- every information on box lable shall be
cross- verified from the drug store logbook and dispensing records.
 General information - IP’s related documents also include
 GMP certificates
 Checklist of IP’s receipt
 Queries resolution form with mail communication
 Shipment documents with the courier receipt
 NOC/ TL licences 22

Sr. 28, 29 and 30
28. Deviation Form
- all deviation shall be cross-verified from the deviation logbook.
- all deviation must be closed during the audit.
29. Laboratory parameters with normal adult reference value Ranges
- Normal reference range value- find the reference laboratory used
during screening and post safety sample analysis and for only lab
document can be compiled or not.
- if two lab used then the normal value range must be compiled for
both labs.
- Additional test performed during the screening and post safety-
normal ranges must be compiled.
23

Sr. 21, 22, 23 and 24
21. Randomization Schedule
- Original Randomization schedule
22. Dispensing Labels
- Dispensing label for all period
- Check every page for completeness (Dated sign)
23. IP Accountability Record at the Site
- Drug-store Logbook photocopy
- Check the IP’s accountability – Calculate the same and match.
24. Vaccutainer's Label
- Label for all period
- Check every page for completeness (Dated sign) 24

Sr. 25, 26 and 27
25. Telephone Notes
- Any trial related communication to sponsor/ investigator/
delegated study personnel/ contract personnel/ IEC/IRB through
telephone.
- if any details about telephone note is referenced captured in
deviation form then same has been compiled with the deviation
form not in this section.
26. Mails
- mail communication regarding the trial (within company)
27. Memo to File
- all memo to file (True copy of memo to file can be accepted)
- if any details about memo to file is referenced in deviation form
then same has been compiled with the deviation form not in this
section. 25

Sr. 30 , 31 and 32
30. List of tests performed during screening
31. Standard Meal Menu for subjects
- Check it from the actual selection of meal menu and CRF.
32. Protocol Training Details Form and Delegation of Job Task for
Study
- Check every personnel training and delegation date
-Every personnel shall delegate and trained on protocol before
performing any activity.
- Eg. Period 01 First Activity as per JD
Period 02- First activity as per JD
26

Protocol Delegation and training
27
Role Activity
(Cross verified
from-Document)
Date of
activity
Date of training and
delegation
CRA Reporting and
ICF distribution
form
18th Sep 18 CRA1- 15th Sep 18
CRA2- 18th Sep 18
CRP (Physician) Clinical
examination
during Check-in
18th Sep 18 CRP1- 18th Sep 18
CRP2- 19th Sep 18
Phlebotomist Alco and urine
abuse form and
BCR
18th Sep 18
19th Sep 18
PH1- 19th Sep 18
PH2- 19th Sep 18
Contract
Phlebotomist
BCR
Alco and urine
abuse form
(Sometime)
19th Sep 18
18th Sep 18
CP1- 19th Sep 18
CP2- 18th Sep 18
Considered
activity
Time

Sr. 33, 34 and 35
33. Subject Screening Log
- Selected list for project
- Check the enrollment log from the VPMS and check every VIN
from enrollment.
- at least check enroll subject which to be selected and enrolled.
34. Subject Enrollment Log
- Check the form with the VPMS enrollment log
- Check the subject number must be serial.
35. Subject Identity card (photocopy)
- check al the ID card with enrollment log.
- Check every subject signature with VPMS
28

Sr. 36, 37 and 38
36. Safety Sample Requisition
-Post safety – Check all the subject samples those are collected
-Individual safety sample requisition can be compiled.
37. Sponsor Agreement
- Sponsor agreement-check the signed pages
- page no 06 and 07 may be missing- this not findings
38. Others
- Sample Segregation related documents
- Sample transfer form
-check the total number of sample and missing sample details – data logger print-out with
PI dated sign
-ICF presentation DVD’s
-Eurotherm print-out (First dosing to sample transfer)
-monitoring report
-Monitoring visit log
- Compensation calculation form
29

30

Review of essential documents (TMF BABE).

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