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regulations Compliance form (PART1) version1 dated 11 Aug 2011. doc.doc
UK Regulations Compliance Form (Part 1)
ISF / TMF Essential documentation for PI, CI & sponsor oversight
Protocol number
Trial Title
Name of CI / PI
Site Name
UK Regulation Compliance form – Part 1 version 2 dated 05 March 2012
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Table of contents
1.
2.
3.
4.
5.
6.
7.
8.
9.
Rationale: .................................................................................................................................3
Scope: ......................................................................................................................................4
Site Contact Details: ................................................................................................................5
Guidance on completing this TMF/ISF template: ...................................................................5
TMF/ISF Section review: ........................................................................................................6
Data Confidentiality and electronic systems: ........................................................................12
Corrective and Preventative Actions: ....................................................................................13
Signatures: ............................................................................................................................. 13
References: ............................................................................................................................14
Acronyms





CI: Chief Investigator
PI: Principal Investigator
TMF: Trial Master File (for CI site)
ISF: Investigator site file (for PI site)
JRO: Joint Research Office
UK Regulation Compliance form – Part 1 version 2 dated 05 March 2012
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1.
Rationale:

The Department of Health, (MHRA) and the sponsor (UCL), expect CIs/PIs to demonstrate
UK CGP Regulation Compliance. To ensure this happens, Universities conducting clinical
trials of Investigational Medicinal Products in the UK are inspected by the MHRA every 2
years. As a PI, CI when you complete, review and sign this document, you
demonstrate to your MHRA inspector and your UCL Compliance Oversight Advisor
that you have UK Regulation Compliance trial “oversight”.

This UK Regulation Compliance form (Part 1) is a tool designed by JRO to help the PI's
teams to assess some important aspects of the trial's compliance with the UK
Regulations underlying clinical trials in the UK.

This form must be completed prior to initiation by the site personnel and sent to JRO
representative

To address the findings proposed corrective/preventive actions should be listed by the PIs,
CIs in the report. The completed report must be returned to the JRO who will review it
NB. Failure to comply with the Oversight form (necessary to evidence compliance with
statutory requirements) may lead to the withdrawal of UCL Sponsorship and R&D
approval and suspension of the trial.
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2. Scope:
Risk level associated to the project for the purpose of UK Regulation compliance trial
oversight/monitoring:
Risk Level
Risk Level A
Risk Level B
Risk Level B
Risk-based
monitoring strategy
level
Phase 4 (Low Risk)
Phase 3 (Medium Risk)
Phase 2b (Medium risk)
MINIMUM self-monitoring
requirements by site
UK Regulations Compliance
assessment form: to be updated
every two months by site
Send form to JRO - once a year
Visit by JRO: one /year (if deemed
necessary from the review of the UK
Regulations Compliance form
required)
UK Regulation Compliance
assessment form: to be updated
every two months by site
Source Data
Verification
(SDV) by site
25% patients
100% consent form
review
50% patients
100% consent form
review
Send form to JRO - once in 6 months
Visit by JRO: two / year (if required)
UK Regulation Compliance
Assessment form: to be updated
every two months by site
Risk Level C
Phase 2a (High risk)
Send form to JRO - once in 6 months
Visit by JRO: two / year
+
Trial status Oversight form – every
two months
Trial specific monitor
Risk Level C
Phase 1: (High risk)
Trial specific monitor
50% patients
100% consent form
review
Trial specific
Trial specific
Risk category: (please enter the risk category as per the above table)
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3. Site Contact Details:
Job description
Person acting as site monitor
CI / PI
Contact details (please print)
Name
Email Address
Phone number
Name
Email Address
Phone Number
4. Guidance on completing this TMF/ISF template:
 Please ensure all sections are complete and all questions answered prior to sending the form
to the JRO for review
 Kindly check that documents have the following:
 Date
 Version Number
 Page Number
 To complete the form:
 Insert Y - If a document is present in the CI TMF
 Insert N – If a document is not present
 Insert Version and date for each document
 Insert NA – if not applicable to the trial
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5. TMF/ISF Section review:
(For ISF reviews, please delete the sections highlighted in blue)
TMF SECTION
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
1.0 SPONSORSHIP/JRO Documents
First Contact Questionnaire
Sponsorship Letter (s)
Legal Representative Letter of Engagement (if applicable)
Insurance Registration Form
Insurance/Indemnity Letter
Peer Review
Comments from JRO review
2.0 FUNDING AND AGREEMENTS
IMP
IMP Supply Agreement
Technical Agreements (i.e. manufacturing/QP release,
packaging, radiolabelling, IMP importation)
Other
Central Services
Central Laboratory Services Agreement/ Material Transfer
Agreement if not with the CTSA (if applicable)
CRO Agreement / Service Level Agreement (if applicable)
Randomisation / Code break agreements (if applicable)
Other
Funding
Funding – Grant Application
Funding – Grant Award
Funding agreement
Other
Responsibility Assignments (note CTSAs maintained in section
18)
Sponsor-CI Agreement
Legal Representative-Sponsor Agreement
Other
Miscellaneous
Confidentiality agreements
Other
Comments from JRO review
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3.0 Research Ethics Committee (REC) and Medicines
& Healthcare products Regulatory Agency (MHRA)
(please file in chronological order and clearly label each submission
separately)
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Initial signed application and supporting documentation to REC
(including cover letter, REC validation letter, favourable/
provisional/with conditions letter / response to conditions of
approval)
Initial signed application and supporting documentation to
MHRA (including cover letter, validation letter, acceptance/with
conditions/grounds for non-acceptance letter /response to
conditions of approval/non acceptance)
Substantial and Non Substantial Amendment s (including where
applicable, Signed Annex 2, Supporting Documents, cover
letter, favourable opinion letter /with conditions, response to
conditions of approval)
Log of Amendment(s) (non-substantial and substantial)
Annual Progress Report to REC and acknowledgement
Serious Breach notifications
End of Trial Notification to REC and MHRA
Final Report Notification and Supporting Documents
Comments from JRO review
5.0 PROTOCOL
Current Approved Protocol & Signature Page
Superseded versions and Signature Pages
Protocol Development Documentation
Comments from JRO review
4.0 PROTOCOL
Current Approved Protocol & Signature Page
Superseded versions and Signature Pages
Protocol Development Documentation
Comments from JRO review
5.0 PATIENT/SUBJECT INFORMATION (sites to hold
relevant documents on letter headed paper)
Sponsor Review/Approval of following documents:
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Template Patient/ Information Sheet and Consent Form (PIS)/
ICF
Template GP Letter
Other
Current Approved Template Patient/ Information Sheet and
Consent Form (PIS)/ICF, GP letter
Superseded versions of Template Patient/ Information Sheet
and Consent Form (PIS)/ICF, GP letter
Template Quality of Life Questionnaires (validated NHS or trial
specific if applicable)
Superseded versions of Template Quality of Life Questionnaires
(validated NHS or trial specific if applicable)
Template Patient Diaries (if applicable)
Superseded versions of patient diaries
Original Signed Informed Consent Forms (per patient/donor)
Other
Comments from JRO review
6.0 CLINICAL TRIAL IMP Documentation
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Summary of drug arrangements
Current Product Information (Full/Simplified IMPD)
Current IMP Safety Information document (IB or SPC)
Superseded version of Product Information
Superseded version of IMP Safety Information document (IB or
SPC)
Sample of Approved Label
MA (IMP) Licence (if applicable)
Certified QP Release Statement (if applicable)
QP declaration (if applicable)
IMP Certificate of Analysis (if applicable)
TSE Certificate (if applicable)
Master Randomisation List (if applicable)
IMP Prescription Template
IMP Accountability Log Template (if applicable)
IMP Destruction Log Template (if applicable)
Temperature Log Template (if applicable)
Temperature Deviation Log (if applicable)
IMP Recalls
Comments from JRO review
7.0 DATA MANAGEMENT
UCL Data Protection Application Form
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UCL Data Protection Registration Confirmation
Current Approved CRF
Superseded versions of CRFs
CRF Review/ approval checklist signed by CI and statistician
Data management plan/SOP
Database validation documentation (if applicable)
Data Query documentation (if applicable)
Completed CRFs, Diary Cards and Quality of Life
Questionnaires
Comments from JRO review
8.0 STATISTICS
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Statistician letter of engagement
Statistical Review
Statistical Analysis Plan (if applicable)
Interim Data Analysis
Final Data analysis
Comments from JRO review
9.0 TRIAL OVERSIGHT COMMITTEES (if applicable)
Trial Management Group (TMG) Reports/Minutes
Data Monitoring Committee/Independent Data Monitoring
Committee (DMC)/(IDMC) reports/minutes
Trial Steering Committee (TSC) reports/minutes
Terms of Reference/Charters for above Committees (if
applicable)
Comments from JRO review
10.0 PUBLICATIONS
Current Results + Related publications
Comments from JRO review
11.0 PHARMACOVIGILANCE
Serious/Adverse Events Log (N.B. for Phase I trials all AEs
should be recorded in the log)
Sample SAE form and pregnancy form
JRO SOP for the Recording and Reporting of (Protocol and
GCP) deviations, violations, serious breaches and urgent safety
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measures
Completed Serious Adverse Events (SAEs) and e-SUSAR
forms and logs
Completed Pregnancy Reporting Form
Notification of Urgent Safety Measures
24 hrs contact card for blinded trials
Emergency Un-blinding SOP (if applicable)
Notification of Safety Information to Investigators and relevant
journal information regarding IMP
Development Safety Update Report (DSUR) and documentation
of submission to MHRA and REC.
Comments from JRO review
12.0 MONITORING
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Trial Site Initiation Report/letter/slides
Pharmacy Initiation Summary letter
Letter/email of Intent to Monitor Site (site visits only)
Sponsor Monitoring Reports (site visits only)
Completed UK Compliance reports from Site
CI’s review of PI UK compliance reports
JRO review of CI/PI UK compliance reports
Trial Monitoring Visit Log
Trial Close Out Checklist
Related Correspondence
Comments from JRO review
13.0 AUDITS & INSPECTIONS
Letter of Intent to Audit by Sponsor Rep or External Rep
Audit Summary Report for Site (where applicable to that site)
Comments from JRO review
14.0 CORRESPONDENCE
Emails/Letters
Phone call logs
Comments from JRO review
15.0 CENTRAL LABORATORIES/SAMPLES
Accreditation Certificates/Conformity Documentation
Other
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Comments from JRO review
16.0 PROCEDURAL DOCUMENTS
Y/N
/NA
Version Number / Date /
Missing
Y/N
/NA
Version Number / Date /
Missing
Trial Specific SOPs (if applicable)
JRO SOPs
Comments from JRO review
17.0 SITE SPECIFIC DOCUMENTS (per site)
Agreements
CTSA (Clinical Trial Site Agreement including
pharmacy/laboratory and material transfer agreement)
Other
NHS Permissions (UK sites only)
Copy of signed SSI form
Copy of signed NHS permission Form
Local R&D NHS Permission Letter
Local R&D Substantial Amendment submission/
approvals/acknowledgement
Site Staff
Staff Signature and Delegation of Tasks Log
CI/PI CVs and GCP certificate(s)
Staff CVs and GCP certificates (if CI site only)
IMP (Note may be located in separate pharmacy file)
Local dispensing/pharmacy procedure SOPs
IMP Ordering and Shipping Records
Completed IMP prescriptions
IMP Accountability Form – completed
IMP Storage Records
IMP Temp records
IMP Destruction Log - completed
Laboratory
Local Laboratory Certification/Accreditation (if applicable)
Laboratory Reference Ranges (if applicable)
Sample Retention Records
Site Patient Activity
Open to recruitment letter
Completed Patient screening log
Completed Subject Enrolment, Withdrawal and Completion log,
Subject ID Code List
Protocol Deviation log
Comments from JRO review
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6. Data Confidentiality and electronic systems:
Electronic data:
Are all Networked computers used for this trial password protected?
Is any data stored on a removable hard drive or lap top?
If yes, what security arrangements or back up procedures are in
place?
What database software are you using to store your trial data?
(if a database is in development please specify type)
Please outline who designed (or will design) the database
Do all data items listed in the Database match those collected in the
CRF and as per approved protocol?
Is all electronic data pseudononymised? (linked via an identifier e.g.
trial number/initials, )
Do you have a Database Validation plan and authorised sign-off
plan in place in the TMF?
e.g.

safety of the electronic database

compliance with UK Regulations,

a test database created with test data entered,

a secure login, authentication, correct implementation of
user privileges and

auditing checks
Is your trial database stored on the UCL or UCLH server?
If other please specify:
Who is responsible for quality control checks of data completeness
prior to analysis?
Is it possible to lock your database when all data is checked and
complete?
Do you use any other databases for this trial? (e.g. recruitment)
Comments from JRO review
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7. Corrective and Preventative Actions:
Summary of findings from this review dated:
Corrective and
preventative Action
Time line set by
JRO
8. Signatures:
Please email this document to the JRO representative for review prior to obtaining signatures.
Job description
Person completing the form at
site
Print NAME
Signature & Date
Signature
Date
CI / PI
Signature
JRO representative
Date
Signature
Date
QA manager (JRO)
Signature
Date
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9. References:
“Risk-Adapted approaches to the Management of Clinical trials of IMP” MRC/DH/MHRA Joint
Project, 1 April 2011
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