Archiving of the Investigator Site File and Trial Master File, SOP
10, V3 08/03/2021 Page 1 of 12
Title: Archiving of the UCLH Investigator Site File/Trial Master
File SOP Number and Version: UCLH SOP 10, Version 3
Effective Date: 08/03/2021 Review Date: 08/03/2024
For Trust-wide SOPs, please check this is the latest version of the
SOP on the Joint Research Office website:
www.ucl.ac.uk/joint-research-office.
Author: Name: Mona Hassan Position: Research Quality and Safety
Manager, Joint Research Office ___________________________________
Signature Date Approved by: Name: Ferdousi Chowdhury Position: Head
of Research Governance and Compliance, Joint Research Office
____________________________________ Signature Date Authorised by:
Name: Bryan Williams Position: Director of Research
_______________________________________ Signature Date
16.02.2021
DocuSign Envelope ID: 489D5FFC-C352-41A9-A131-A518B6CBB659
Revision Chronology:
Version Number:
Effective date:
Daniel Heather
03/04/2017
SOP updated to include new archiving retention periods for ATIMPs
and CTIMPs; separate archiving process for commercial studies;
further details regarding JRO process for archiving and
clarification on archiving patient identifiable research-related
records.
Stuart Braverman
V2.1 06/09/2017
SOP updated to remove reference to UCL Records Office address and
archiving warehouse, as any archiving requests are solely
coordinated by the JRO and UCL Records team via email. Reference to
UCL Records Office costs have also been removed, as the service is
offered free of charge for applicable research studies. Minor
changes made throughout document. A template Investigator Site File
Contents Checklist has been included as an appendix (Appendix 2) to
aid researchers in maintaining essential documents.
Stuart Braverman
V3 08/03/2021
- SOP updates to include Definitions, Scope and Roles and
Responsibilities section
- SOP has been updated to state that all commercial and
non-commercial ISFs and TMFs may be archived with the UCL Records
Office (provided contractually agreed between site and
sponsor).
- The process for archiving Pharmacy Site Files will exist as a
separate Guidance Document, “Archiving of the Pharmacy Site File”
(further details available via
[email protected]). This is a
separate document which is aimed at Pharmacy staff members
responsible for arranging archiving of the UCLH PSF.
- Section 6 templates, Research Records Transfer Form, has been
separated from this SOP; a flowchart outlining the archiving
process for paper essential documents has been appended. The
template for Investigator Site File Contents has been separated
into a separate template
- Updates to references made throughout document.
Reviewed by: Arti Kara, Research Audit and Quality Officer Tolu
Adebanjo, Portfolio and Database Administrator Colin Penman, UCL
Records Manager Robert Winckworth, Senior Library Assistant
(Records) UCL Records Office Celia St Clair, CCTU Quality Assurance
Manager Kirsty Adams, CRF Quality Assurance Manager Pharmacy
Clinical Trials team (UCLH) Jayne Foley, Head of Records at
UCLH
DocuSign Envelope ID: 489D5FFC-C352-41A9-A131-A518B6CBB659
ACRONYMS ATIMP Advanced Therapy Trial of an Investigational
Medicinal Product CI Chief Investigator CTIMP Clinical Trial of an
Investigational Medicinal Product ECG Echocardiogram GCP Good
Clinical Practice ISF Investigator Site File ISF Investigator Site
File JRO Joint Research Office MHRA Medicines and Healthcare
Products Regulatory Agency Non-CTIMP Any research study that is not
a clinical trial of an investigational medicinal
product PI Principal Investigator QA Quality Assurance R&D UCLH
Research Directorate (formally Research & Development) SOPs
Standard Operating Procedures TMF Trial Master File UCL ROS
Database University College London Records Office System Database
UCL University College London UCLH University College London
Hospitals NHS Foundation Trust 1. DEFINITIONS
Advanced Therapy Investigational Medicinal Product (ATIMP)
Means any of the following medicinal products for human use: a gene
therapy medicinal product, a somatic cell therapy medicinal
product, or a tissue engineered product. If they are being tested
in a clinical trial, they are referred to as ATIMPs. Further
information here.
Archiving (in clinical research)
All essential documents should be archived per applicable
regulatory requirements, and per the site agreement between the
Sponsor and research site. This includes essential documents held
by investigators, sponsors and others involved in the conduct of a
clinical research study (including services departments such as
pharmacy, laboratories, and radiology). Consideration should be
given for the archive of both paper and electronic data (such as
databases). EMA Guideline on the content, management and archiving
of the clinical trial master file (paper and/or electronic)’
(December 2018) should be considered when developing systems for
archive. This document includes guidance relating to the media used
for storage of documents (including requirements when original
records are transferred to electronic media for the purpose of
archive).
Ferdousi Chowdhury, Head of Research Governance and
Compliance.
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Clinical trial of an investigation medicinal product (CTIMP)
Any investigation in human subjects intended to discover or verify
the clinical, pharmacological and/or other pharmacodynamic effects
of one or more investigational medicinal product(s), and/or to
identify any adverse reactions to one or more investigational
medicinal products(s) and/or Study absorption, distribution,
metabolism and excretion of one or more investigational product(s)
with the object of ascertaining its (their) safety and/or efficacy.
All CTIMPs must comply with the Directives 2001/20/EC and
2004/28/EC (these EU directives were transposed into UK law by SI
2004/1031 and SI 2006/1928).
Investigator Site File (ISF) An Investigator Site File (ISF) should
be established at the beginning of each clinical research study at
the participating site. The ISF contains the minimum list of
essential documents that have to be maintained throughout the
clinical trial at a participating site, and is necessary for
effective management and oversight of research at site. The ISF
contains site-specific documents and patient identifiable
information (e.g. signed consent forms, screening logs, etc.).
Further information in Section 8 ICH E6 (R2) Good Clinical
Practice. For single-site studies, the ISF and TMF are often stored
together (although patient identifiable information must be removed
in the event of any Sponsor inspections/audits).
Non-CTIMP A clinical study which does not fall under Clinical and
Advanced Therapy Trials of Medicinal Products (CTIMPs and ATIMPs)
and regulated Devices definitions. Examples are:
- Clinical investigation or other study of a CE marked medical
device falling under ISO 14155
- Basic science study involving procedures with human
participants
- Other clinical trial to study a novel intervention or randomised
clinical trial (RCT) to compare interventions in clinical
practice
- a study administering questionnaires/interviews for quantitative
analysis, or using mixed qualitative/quantitative methodology
- a study involving qualitative methods only - a study limited to
working with human tissue samples (or
other human biological samples) and data (specific project
only)
- a study limited to working with data (specific project only).
Non-CTIMPs must comply with the UK Policy Framework for Health and
Social Care Research.
Sponsor The organisation or partnership that takes on overall
responsibility for proportionate, effective arrangements being in
place to set up, run and report a research project. All health and
social care research should have a sponsor. This includes all
research that involve NHS patients, their tissue or information. A
sponsor can delegate specific tasks to any other individual or
organisation that is willing and able to accept them (e.g.
archiving of the ISF/TMF to research site(s). Further information
here.
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Archiving of the Investigator Site File and Trial Master File, SOP
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Trial Master File (TMF) The TMF is the Chief Investigator’s
(CI)/Sponsor’s central file that does not contain any patient
identifiable information such as screening/enrolment logs and
signed consent forms. The TMF is usually held at the Sponsor’s
coordinating site (usually the Chief Investigator’s office or
Coordinating Centre) and for multi- site trials, copies of
site-specific documents should be kept at each participating site
in an ISF. Most sponsors will provide guidance on the content and
set up of the TMF based on their policies/procedures. The
maintenance of a study file is necessary for effective management
of research studies: 1) during preparation, 2) throughout the
conduct and 3) after the study has ended. The ongoing updating and
maintenance of a study’s essential documents allows for evaluation
of the conduct of the study, and the quality of the data collected.
These documents serve to demonstrate the compliance of the study
team and sponsor with the standards of ICH Good Clinical Practice
(GCP) and with all applicable regulatory and Trust
requirements.
2. BACKGROUND
Archiving is the long-term storage of the essential documents which
are held in the Investigator Site File (ISF) or Trial Master File
(TMF), following the completion of a clinical research study/trial.
The media used to store essential documents must ensure documents
remain complete and legible throughout the retention period and
must be made available to regulatory authorities and for
internal/external auditing purposes upon request. This SOP is
applicable to all clinical research hosted and/or sponsored by UCL
or UCLH. Archiving of the ISF/TMF is arranged via the UCLH/UCL
Joint Research Office (JRO), with the University College London
(UCL) Records Office archiving facility. (Please note there is a
separate SOP for archiving of UCL sponsored CTIMPs, which goes into
further detail: UCL SOP for Archiving Essential Documents relating
to CTIMPs). 3. PURPOSE AND SCOPE
The purpose of this SOP is to guide UCL/UCLH research study teams
through the archiving process for paper clinical trial
documentation. It is the Principal Investigator’s responsibility to
arrange archiving per the protocol, once the study has closed, or
to delegate this to a member(s) of their team. This SOP lays out
the correct archiving storage and retrieval procedures for ISF/TMF
contents (where archiving of the TMF has been delegated by the
Sponsor to UCLH per the site agreement). According to Good Clinical
Practice (ICH-GCP) E6(R2) Guidelines (and subsequent amendments),
all clinical trial information should be recorded, handled, and
stored in a way that allows its accurate reporting, interpretation,
and verification. All CTIMPs, ATIMPs and non-CTIMPs should be
archived in the same manner, but differ on retention period as per
the Sponsor and archive offices retention policies, funder
retention policies or third-party retention requirements:
- Under the current EU Clinical Trials Directive 2001/20/EC, CTIMPs
must be archived for minimum 20 years.
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Archiving of the Investigator Site File and Trial Master File, SOP
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- EU Guidance on GCP for Advanced Therapy Medicinal Products 2009
requires that study documentation must be kept for 30 years after
the expiry date of the product (for traceability documentation
only), or longer if required by the MHRA.
- non-CTIMP studies must be archived for a minimum of 5 years if
they will not be submitted to a regulatory authority. Otherwise, a
further retention period of at least 15 years will be required.
Research staff are encouraged to check their protocol or with their
Sponsor on their specific retention times.
- For research involving children, essential documents should be
archived until three years after the youngest subject reaches 18
years old, or 5 years after the conclusion of the research,
whichever is longer.
Funders, journals, sponsors, and participating organisations will
also have local policies/procedures covering archive requirements,
which must also be followed. Where more than one retention policy
is applicable to a study, the longest retention period will apply.
The Sponsor should provide an index of the documents to be filed in
the ISF/TMF. If the Sponsor does not have an index, the UCLH SOP 8
on Essential Documents and the Study File outlines a list of
documents which need to be filed in the ISF/TMF, depending on study
type. In cases where the PI is also the CI and the Sponsor has
delegated to the CI the archiving of the TMF, then this should
follow the same process as of the ISF. The JRO arranges archiving
of the ISF/TMF for UCL/UCLH sponsored and hosted studies. The JRO
does not arrange archiving of patient medical records collected at
UCLH; these must be archived with UCLH’s medical records archiving
facility, Iron Mountain, rather than within the ISF/TMF. The
following table shows the typical documents collected at site, and
the appropriate archiving locations for documents containing
patient identifiable information:
Document Name Patient Identifiable Information? Y/N
Location of Archiving
Study Documents (e.g. Protocol, patient facing document templates,
superseded documents, regulatory approval letters, study
correspondence with Sponsor/R&D, etc.)
N/A ISF/TMF archiving box
Original signed Consent Forms*
Y ISF archiving box
Quality of Life questionnaires
N ISF archiving box
Travel Expenses Y Patient Medical Notes via UCLH Iron
Mountain
N ISF/TMF archiving box
Investigator Brochure N/A ISF/TMF archiving box
ECG Y Patient Medical Notes via UCLH Iron Mountain - Make a
photocopy and staple together
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Requisition Forms N ISF/TMF archiving box
Master Subject List* Y ISF archiving box
Screening Log (including enrolment and withdrawal logs)
N ISF/TMF archiving box
N ISF/TMF archiving box
*Documents such as Signed Consent Forms and the Master Subject List
containing patient identifiable information may be archived with
the ISF but should be kept separate from the TMF. Please note this
list is not exhaustive; a full list of the document types typically
stored in an ISF/TMF can be found in the UCLH SOP 8 on Essential
Documents and the Study File and its related Appendix. 4. ROLES AND
RESPONSIBILITIES
Role Duties
Principal Investigator (or delegate, per delegation log)
- Responsible for arranging archiving of study records following
study close down at site
Sponsor - Responsible for study close down at site, and archiving
arrangements. In some instances, Sponsor may delegate archiving of
the ISF/PSF to the research site (e.g. UCLH). This should be noted
in the site agreement and costed for prior to site
initiation.
- Provides ISF index sheets/checklists, and folders (where
applicable). In the absence of these, UCLH SOP 8: Essential
Documents for the ISF/TMF may be used.
UCLH/UCL Joint Research Office Data and Information Management team
(
[email protected])
- Responsible for arranging archiving of clinical research files
with the UCL Records Office, following study close down, including
logging archiving requests
- Point of contact for any queries regarding current or previous
archiving requests
- Responsible for arranging retrievals of previously archived
research files.
UCL Records Office (
[email protected])
- JRO’s archiving provider for UCL/UCLH sponsored and/or hosted
clinical research files (e.g. ISF)
- Provide archiving boxes and will arrange UCL Porter collections
of files for archiving
5. PROCEDURE
Archiving of the Investigator Site File and Trial Master File, SOP
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1 Study documents must be archived when the Sponsor has instructed
or contractually agreed for the site to archive the ISF, and after
the UCLH study team have submitted an end of study notification to
the JRO. The actions outlined in the UCLH SOP 9: Study Close Down
must be carried out prior to starting the archiving process, and
following confirmation from the Sponsor.
Sponsor, Investigator
2 Providing that one of the following conditions are met, the
records should be archived via UCL Records Office:
• The legal sponsor for the study is UCL
• The local Investigator holds a contract (honorary or substantive)
with UCL
• The study is hosted at a UCL managed or joint UCL/UCLH managed
facility (e.g. UCL/UCLH Clinical Research Facility; UCL Institute
of Neurology etc.)
• Archiving via UCLH (i.e. UCL Records Office) has been agreed and
costed for within the UCLH site agreement.
• If unsure, please contact JRO for clarification.
UCL Records Office
3 Where the above conditions apply, the member of the research team
who has been delegated to undertake archiving should review the
instructions contained in the JRO Research Records Transfer Form
(Section 6), which are reproduced below for convenience: 1) Please
contact the UCL Records Office via email
(
[email protected]) to request boxes. Boxes not supplied by
the UCL Records Office will NOT be accepted. Box dimensions are as
follows 360mm (L) x 140mm (H) x 255mm (W). Please stipulate:
• Number of boxes required
• Location where boxes should be delivered to 2) Once you have the
boxes, write a temporary running order (in pencil
only) on the front of each box (1, 2, 3). Do NOT write or stick
anything else on the boxes.
3) Place the contents of the ISF/TMF into the boxes. Remove papers
from
folders and lever arch files and remove plastic wallets and rubber
bands as these take up space and deteriorate in long term storage.
If the lever arch file has study information on its spine, this can
be photocopied and placed within the boxes. Coloured paper can be
used between sections if required. ECG, eCRF and clinical reports
on shiny paper can fade over time. Such documents can be
photocopied and validated as certified copies and also placed
within the boxes. Do not place additional boxes (e.g. magazine
files) inside the boxes. Boxes should be filled but should not be
overfull or taped shut.
4) List the box number and contents of that box on the
Research
Records Transfer Form. Complete the form in Microsoft Word format
and email as an attachment to
[email protected]. The form will not
be accepted in hardcopy or as a PDF.
These boxes must be kept in secure, restricted access locations
until collection.
Delegated research team member undertaking archiving
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No research/sponsor/patient identifiable information is allowed on
the outside of boxes. No Sponsor/Site labels may be used. The JRO
and UCL Records Office will not accept any records for archiving
where any of the above has not been followed and in these instances
records will be returned to sender.
4 On receiving the Research Records Transfer Form, a member of the
JRO Data and Information Management team will enter the relevant
information onto the UCL Records Office System (ROS) Database, and
e-mail the delegated research team member the ROS output form,
containing the unique box reference number generated by the UCL ROS
system. There will be one output form per box; therefore, each box
will have its own unique box reference number.
JRO Data and Information Management team
5 The delegated research team member for archiving will insert the
form generated by UCL ROS into the boxes and will e-mail
[email protected] to confirm that this has been done, the number
of boxes, and their current location. Only the unique reference
generated by the UCL ROS should be written outside of the
box.
Delegated research team member undertaking archiving
6 Following confirmation from the research team that the boxes are
ready for collection, the JRO will notify the UCL Records Office,
who will arrange for UCL Porters to collect the boxes from their
current location at a convenient time, and transfer them to the UCL
Records Office for offsite archiving (if you require the address of
offsite storage for monitoring, inspection or auditing purposes,
please contact the JRO or UCL Records Office who can provide this).
Boxes should be placed in an accessible, secured location for the
UCL Porters to collect (contactless). If the boxes are locked away
in storage or an office, then it requires contact with the research
team for handover. Once the boxes have been collected, the research
team must inform the JRO. The JRO will keep a record of when UCL
Records Office have received boxes from research teams.
JRO Data and Information Management team UCL Records Office
7. The JRO will also maintain a record of the box reference numbers
and will routinely audit archived studies to ensure the
requirements of this SOP have been met. The overall archiving
process time takes a maximum of 4 weeks to complete.
JRO Data and Information Management team
8. Archiving and Retrieval of Electronic Records Consideration
should be given for the archive of both paper and electronic data
(such as databases). EMA Guideline on the content, management and
archiving of the clinical trial master file (paper and/or
electronic)’ should be considered. This document includes guidance
relating to the media used for storage of documents (including
requirements when original records are transferred to electronic
media for the purpose of archive). All research data on Epic UCLH
will form part of the patient’s medical record and will continue to
be accessible to the UCLH study team during the required archiving
retention period. IT systems which were utilised prior to Epic and
then discontinued upon Epic implementation will have its data
archived within UCLH’s data warehouse,
Delegated research team member undertaking archiving
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for up to 30 years as per legal requirements. Requests for
retrieval of data from legacy IT systems can be raised via the ICT
Service Portal:
a) Log on to the ICT Service Portal (circular orange icon) on the
desktop b) Select ‘Service Catalogue’ c) Select ‘System Specific
Support’ d) Select ‘Request for patient data from legacy systems’
e) Complete the form f) The data will then be retrieved from UCLH’s
data warehouse and
shared with the requester via email within seven working days For
further information regarding data archiving, please contact
[email protected].
9. Pharmacy Site File (PSF) The pharmacy site file does not need to
be archived at the same time as the ISF as it is generally ready to
be archived at an earlier stage. However, if the pharmacy site file
is ready to be archived at the same time as the ISF, then they can
be archived together. If ready earlier than the ISF, the PSF is
arranged by the UCLH Pharmacy Clinical Trials team, via the UCLH
archiving provider Iron Mountain. To discuss archiving, study teams
need to contact the Pharmacy Clinical Trials Team via the following
email address:
[email protected]. The PCT team will be
responsible for archiving he PSF on behalf of the PI. Sponsors and
study teams must engage with Pharmacy prior to starting the
archiving process so they can remove IMPs. There should also be a
File Note within the ISF referencing the location of the Pharmacy
Site File’s location (if archived elsewhere).
Delegated research team member undertaking archiving Pharmacy
Clinical Trials Team
10. Patient Hospital/Medical Notes Please refer to the UCLH Records
Management Policy. Under NO circumstances should patient/medical
notes be archived by the UCL Records Office. UCLH patient medical
notes are archived via Iron Mountain; please contact the UCLH
Medical Records team via
[email protected] to arrange.
Other research related paperwork containing patient identifiable
data (for example signed consent forms, lab reports and ECG data)
may be archived in accordance with this SOP. Source data outside of
these examples are recorded/uploaded to Epic, as per UCLH
policy.
Delegated research team member undertaking archiving
11. Retrieval of boxes In the event that boxes need to be retrieved
from archiving, study teams should e-mail
[email protected] with
the study title and R&D/EDGE reference number and reason for
retrieval, as well as details of where the boxes should be
delivered to. The JRO Data and Information Management team will
pass this information onto the UCL Records Office and provide them
with the unique box reference number(s); the UCL Records Office
will contact the study team to arrange retrieval from the archiving
facility and UCL Porter delivery of the archived boxes, and
subsequent return of boxes to the archiving facility. The JRO Data
and Information Management team will maintain a record of the
retrieval request for audit purposes. Destruction of Archived Boxes
The UCL Records Office will contact the study team/JRO when the
stated archiving time for a box has expired to see if documents can
be destroyed.
JRO Data and Information Management team
The UCLH PI/CI (where UCL/UCLH is acting as Sponsor) should confirm
if destruction can proceed (in accordance with Sponsor confirmation
and applicable archiving retention periods). If further archiving
time is required, the PI/CI (or delegate) should inform the UCL
Records Office via
[email protected]. According to ICH GCP
E6 (R2) Guidelines (Section 5.5.12) it is the Sponsor’s
responsibility to consult the Investigator/institution when
documents no longer need to be retained.
6. IMPLEMENTATION & TRAINING
Staff following this SOP must confirm they have read and understood
the procedures outlined above by completing their relevant
departmental training log as a record of acknowledgement.
5. PUBLICATION & COMMUNICATION
The latest version of this SOP is authorised and published on the
JRO website:
http://www.ucl.ac.uk/joint-research-office. 6. TEMPLATES ASSOCIATED
WITH THIS DOCUMENT
Document Stored
JRO Website (R&D SOPs, Policies and Templates page)
2. ISF/TMF Index Checklists JRO Website (Sponsor or R&D SOPs,
Policies and Templates page)
7. REFERENCES
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8. APPENDICES
Appendix 1: Flowchart of Archiving Process for Paper Essential
Documents
1) Sponsor informs UCLH Study Team that the ISF can be
archived
2) UCLH Study Team first follows UCLH SOP 9: Study Close Down
3) UCLH Study Team checks that the study meets at least 1 of the
following conditions:
• The legal sponsor for the study is UCL
• The local PI holds a contract (honorary or substantive) with
UCL
• The study is hosted at a UCL managed or joint UCL/UCLH managed
facility (e.g. UCL/UCLH Clinical Research Facility; UCL Institute
of Neurology etc.)
• Archiving via UCL Records Office has been agreed and costed for
within the UCLH site agreement
4) UCLH Study Team reviews instructions on Research Records
Transfer Form (form can be found on the JRO website)
5) UCLH Study Team contacts UCL Records Office via
[email protected] to request archiving boxes
6) UCLH Study Team places contents of ISF in boxes and labels
boxes, as per guidance detailed in this SOP
7) UCLH Study Team completes the JRO Research Records Transfer
Form
and emails it as a Word Document to the JRO via
[email protected]
8) JRO will enter the relevant information onto the UCL ROS
Database and email the UCLH Study Team with the unique box
reference number generated and a receipt (ROS output form) - 1 ROS
output form per box
9) UCLH Study Team inserts the ROS output form into the archiving
box and writes the unique box reference number on the outside of
the archiving box
10) UCLH Study Team emails JRO via
[email protected] to confirm
the above steps have been completed and the box(es) is/are ready
for collection
11) JRO will arrange for the UCL Porters to collect the box(es)
from their current location to be transferred to the UCL Records
Office
Yes No Please speak to Sponsor
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