title: archiving of the uclh investigator site file/trial ... · docusign envelope id:...

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
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.
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.
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.
- 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
Requisition Forms N ISF/TMF archiving box
Master Subject List* Y ISF archiving box
Screening Log (including enrolment and withdrawal logs)
*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
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
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.
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.
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,
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.
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.
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
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