research governance policy practice guidance note study ... · (sop)/pgn log to document any study...

Northumberland, Tyne and Wear NHS Foundation Trust RGP-PGN-06 – Study Documentation and Archiving p- V01 – Iss 4 – Nov 18 Part of NTW(O)47 – Research Governance Policy

Research Governance Policy Practice Guidance Note Study Documentation and Archiving - V01

Date Issued Planned Review PGN No:

Issue 1 – Nov 14

Issue 2 – Nov 17

Issue 3 – May 18

Issue 4 – Nov 18

May 2019 RGP-PGN-06

Part of NTW(O)47 – Research Governance policy

Author/Designation Simon Douglas - Senior Manager for Research Innovation and Clinical Effectiveness

Responsible Officer / Designation

Medical Director

Section Contents Page No

1 Introduction and Purpose 1

2 Scope 1

3 Trial Master File 1

4 Investigator Site File 2

5 Archiving 3

5.2 Responsible Personnel 3

5.3 Definitions 5

5.3.1 Essential Documentation 5

5.3.2 Site Closure 5

5.3.3 Study Closure 5

5.4 Procedure 5

5.4.1 Trust Master File 5

5.4.2 Investigator Site File (ISF) 5

5.5 Duration 6

5.6 Storage 6

5.7 Archive procedure 7

5.8 Retrieval From Archive 7

5.9 Destruction Of Archived Documents After Storage 7


Appendices – Attached to PGN

Document No:

Description Issue Issue Date

Review date

Appendix 1 Trust Master File (TMF) / Investigator File (ISF) Contents

1 Nov18 May 19

Appendix 2 Study Archiving Checklist 1 Nov18 May 19

Appendix 3 NTW storage facility information 1 Nov18 May 19

Appendix 4 Archive log 1 Nov18 May 19

Appendix 5 Archive Process 1 Nov18 May 19

Appendix 6 Box label 1 Nov18 May 19

Appendix 7 Chain of custody 1 Nov18 May 19

Northumberland, Tyne and Wear NHS Foundation Trust 1 RGP-PGN-06 – Study Documentation and Archiving p- V01 – Iss 4 – Nov 18 Part of NTW(O)47 – Research Governance Policy

1 Introduction and Purpose 1.1 The purpose of this practice guidance note (PGN) is to ensure a consistent

approach to creating, filing and maintaining essential documents for the trial master file (TMF) and investigator site file (ISF) and the procedure for archiving these resources within Northumberland, Tyne and Wear NHS Foundation Trust (the Trust/NTW)

1.2 This PGN describes the procedure for setting up TMF and ISF and details the

essential documents that should be maintained within these files. This document is primarily aimed at Clinical Trials, Investigational Medicinal Products (CTIMPs), falling under the remit of the EU Clinical Trials Directive, Medicines for Human Use (Clinical Trials) Regulations 2004, but it is also relevant to any project conducted within the Trust, which falls under the Research Governance Framework to ensure the safety and well-being of participants is maintained.

1.3 The document also provides guidance on the archiving (retention) requirements for essential documents of clinical trials sponsored and hosted by NTW, in accordance with regulatory requirements (for CTIMPs, the Medicines for Human Use (Clinical Trials) Amendment Regulators 2006 confirm the legal obligations for archiving essential documentation).

2 Scope 2.1 This PGN applies to all personnel carrying out clinical research or research

related activities within the Trust. 3 Trial Master File (TMF) 3.1 The TMF shall consist of essential documents which enable both the conduct of

a clinical trial, and the quality of the data produced, to be evaluated according to Article 16 of Directive 2005/28/EC. These documents serve to demonstrate the compliance of the investigator, sponsor and monitor the standards of Good Clinical Practice and with all applicable regulatory requirements.

3.2 The Chief Investigator (CI) or delegate must establish the TMF at the beginning

of the trial and prior to patient recruitment. They are responsible for updating the TMF as the trial progresses. The TMF must:

• Be kept in a secure location

• Contain essential documents that are legible, accurate and complete These should be signed and dated

• Contain an index at the front of the file to show which documents are stored in the TMF. If an essential document is not considered applicable, this should be documented on the TMF index

• Reference the location of any documents which are considered applicable but are located out with the TMF. A file note should be added to the relevant TMF section


• If relevant the TMF should contain a Standard Operating Procedure (SOP)/PGN log to document any study specific SOPs/NTW PGNs in use

3.3 The TMF should be updated as the trial progresses and filing should be done in

a timely manner. Maintenance of the TMF includes:

• Ensuring the TMF is made available for the purposes of monitoring or audit by the sponsor and regulatory inspections

• Prior to archive all outstanding essential documents and file notes should be added to the TMF and the TMF index completed (the archiving process should, where appropriate, follow NTW archive process as outlined in this document)

4 Investigator Site File (ISF)

• If the TMF and ISF are filed centrally there is no requirement to set up a separate ISF as long as it is clear which documents in the TMF relate to each site

4.1 The ISF should be established at the beginning of the study prior to patient recruitment and should:

• Be kept in a secure location

• Reference the location of the pharmacy file (as appropriate) if this is separate from the ISF. The pharmacy file must be archived with the main ISF

• Contain essential documents that are legible, accurate and complete

• Contain an ISF checklist at the front of the file to show which documents are stored in the ISF. If a document is not considered applicable, a reason for this decision should be documented on the checklist

• Reference the location of any documents which are considered applicable but are located outwith the ISF. A file note should be added to the relevant ISF section

• If relevant, contain an SOP/PGN log to document and study specific SOPs/NTW PGNs in use

4.2 The ISF should be updated as the trial progresses and filing should be done in a timely manner. Maintenance includes:


• Ensuring the ISF is made available for the purposes of monitoring or audit by the sponsor and for regulatory inspection

• Once the study has closed the ISF should be reviewed to ensure that all the required documents are present and complete

• Provision of the completed ISF index to the sponsor prior to archiving

the ISF 4.3 The documents should be archived in an appropriate room or locked cupboard

(consider fire protection without water sprinkler systems, water protection for humid conditions, pests etc.). The room must be secure with access only by authorised personnel.

4.4 The structure and contents of the ISF are listed in Appendix 1 5 Archiving 5.1 Appropriate arrangements must be in place to archive relevant study

documents/data at the end of a study in accordance with regulatory requirements. For CTIMPs, the Medicines for Human Use (Clinical Trials) Amendment Regulators 2006 (Statutory Instrument 2006, No. 1928) confirm legal obligations for archiving essential documentation. All investigators who wish NTW to act as archive supplier must adhere to NTW processes and comply with this PGN.

5.2 Responsible Personnel 5.2.1 It is a legal requirement that the sponsor appoints a named individual within the

organisation to be responsible for archiving the documents which are, or have been, contained in the TMF and that access to these documents shall be restricted to those appointed individuals, auditors and/or inspectors.

5.2.2 Where NTW are to be responsible for archiving, either as a sponsor

responsibility or as appropriately delegated, arrangements need to be discussed at the trial agreement phase of registration/approval. Where NTW are responsible for archiving, specific roles will be attributed to the R&D team: Senior Manager for Research Innovation and Clinical Effectiveness • Agree archiving arrangements at CTA stage

• Agree any archiving payments due to NTW

• Oversee and approve the study documentation and archiving PGN

• Agree study closure meeting process

• Confirm destruction arrangements

5.2.3 Research Governance Facilitator


5.2.3.1 The Research Governance Facilitator is the named archivist for NTW. The archivist’s main responsibilities include:

• First point of contact for any archive queries or requests for document

retrieval from archive facilities

• Coordinate/lead study closure meeting and process

• Maintain and update the archive register and associated documentation

• Conducting the pre-archive audit

• Annual attendance at secondary storage facility meeting to ensure they remain fit for purpose

• Maintain and update the study documentation and archiving PGN

• Coordinate chain of custody documentation

• Coordinating retrieval of archived documents when required

• Confirm and agree destruction arrangements

• Retain destruction certificate (issued by secondary storage facility)

5.2.3.2 It is the responsibility of the sponsor to inform NTW as to when documents no longer need to be retained. The sponsor should notify investigators in writing when their trial records can be destroyed. If an investigator becomes unable to take responsibility for their essential documents (e.g. relocation, retirement etc.) the sponsor should be notified in writing of this change and informed as to whom the responsibility has been transferred.

5.2.3.3 The CI is responsible for the archiving of essential documents as part of the

TMF. For multi-centre studies the CI is also responsible for the archiving of essential documents at the participating sites, although this may be delegated to the Principle Investigator (PI) at that site through a documented agreement. Any subsequent transfer of ownership and responsibility for data retention and archiving must be agreed and documented, including where a CI/PI leaves an institution during the period of archive.

5.2.3.4 It is the responsibility of the CI to inform the PIs at each site as to when these

documents are no longer required to be retained and may be destroyed. 5.3 Definitions


5.3.1 Essential documentation

• Documents which individually and collectively permit evaluation of the conduct of the study and the quality of the data produced. Essential documents show whether the trial has been conducted in accordance with applicable regulatory requirements

5.3.2 Site Closure

• The process of ensuring all study-related activities at a participating site are reconciled and/or complete

5.3.3 Study closure

• The process of ensuring all study-related activities are reconciled and/or complete

5.4 Procedure 5.4.1 Trust Master File

• The TMF, including all essential documentation should be archived as soon as it is practicable after the site/study closure, after the final closeout visit, issue of closeout report and final written report and once the Research Ethics Committee (REC)/licensing authority is informed that the trial has ended.

5.4.2 Investigator Site File

• ISF can be archived as soon as it is practicable after the sites closure, usually following a site closure visit. In multi-centre study’s, PIs will be informed when their ISF can be archived

• The ISF must include an instruction that records should be not destroyed until notified by the sponsor and that this will be at least 5 years following the conclusion of the trial

• Where source data is held in medical records which are in current use, and/or subject to local policies for archive and retention, it must be established that these are marked as clinical trial records and will be managed appropriately

• (Appendix 2 Study archiving checklist provides a list of the documents required for archive)

5.5 Duration


5.5.1 The sponsor of a CTIMP is responsible for determining the archive duration of that study’s documentation. In line with the regulations, all essential documents must be retained for at least 5 years after the completion of the study. If the study involved minors under 18 years old, essential documentation should be archived until 3 years after the youngest subject reaches 18 years old, or 5 years after the conclusion of the study, whichever is longer.

5.5.2 Where NTW is not the study sponsor, it is the responsibility of the sponsor to

determine and inform the NTW archivist and study PI if essential documents are to be retained for longer.

5.5.3 When storing TMF/ISF, notice must be given to the following requirements:

• Essential documentation must be stored in a way that ensures they are available for future audit or inspection

• Essential documents must remain complete and legible • Named individuals should be identified as having responsibility for

the archived files, including any transfer of this responsibility for the duration of the study

• Data must be stored in a way to ensure the confidentiality of

participants remains protected

5.6 Storage 5.6.1 Please refer to Appendix 3 – NTW Storage Facility Information, for specific NTW

storage archive and arrangements. 5.6.2 Prompt retrievals should be possible. Plans for archiving trial documents should

be made in the design phase of a trial and costs of storage should be considered. The storage of the sponsor’s documentation may be transferred to a subcontractor but the ultimate responsibility for the quality, integrity, confidentiality and retrievability of the documents resides with the sponsor (CPMP/ICH/135/95, 5.2.1). This means that the sponsor should audit the site and satisfy itself and document that the storage is appropriate.

5.6.3 Access to archives will be restricted to authorised personnel. Any change in the

ownership and location of the documentation will be documented in order to allow tracking of the stored records.

5.6.4 An archive index/log will be maintained to record all essential documents that

have been entered into the archive and to track and retrieve documents on loan from the archive. The investigator should make the sponsor/trial organisers aware of the storage arrangements for the documents to be stored at investigator sites. If the investigator becomes unable to store their essential documents, the sponsor/trial organisers should be notified in writing so that alternative storage arrangements can be agreed. If the investigator is no longer able to maintain custody of their essential documents, the sponsor/trial


organisers should be notified in writing and the investigator/institution see to it that appropriate arrangements can be made.

5.6.5 Appendix 4 shows the archive log fields. 5.7 Archive procedure 5.7.1 Please see Appendix 5 for the archive procedure for NTW 5.7.2 Please see Appendix 6 – archive labels for boxes 5.8 Retrieval from archive 5.8.1 Retrieval from internal storage

• Researchers are required to make a formal request via email, at least 1 week in advance, to have access to the archived documents. Access will be at the discretion of the R&D archivist

5.8.2 Retrieval from external storage

• Researchers must make any request for retrieval formally to the R&D archivist, at least 3 weeks in advance, for access to the archived documents. Retrievals from archive are restricted to a limited number of circumstances and should be kept to an absolute minimum. This may include audit of the results required to comply with a Department of Health, Regulatory Authority, NTW or other quality assurance request

• The transfer of records will be documented and monitored. Please see Appendix 7 for the NTW chain of custody document

5.9 Destruction of archived documents after storage 5.9.1 Each box going into storage will be allocated a destruction date – allocation will

be in accordance with the archive requirements for the individual study. 5.9.2 The destruction date will be logged on the R&D archive register and in the

corporate records log held in the Records Department. In advance of this date, the NTW secondary storage supplier will contact the Trusts Records Manager who in turn contacts the R&D archivist, to clarify if the destruction date remains valid. R&D will either confirm the destruction date or set a new date.

5.9.3 The secondary storage supplier will carry out the destruction of the box contents

and will issue a certificate of destruction which R&D will keep for a 5 year period. All information will be recorded on the archive log.


Appendix 1

Protocol Title

Protocol number: R&D number:

EudraCT number: REC ref number:

ISRCTN: Chief Investigator:

Principal Investigator:

(Applicable for Investigator Site File)

General Guidance: * All documents must be version controlled. Superseded versions can be marked by a line through the front cover, noting “SUPERSEDED”, initialled and dated. * Correspondence and version-controlled documents must be filed in chronological order with the most recent on top. * Some sections can be sub-divided to ease filing. * For study with multiple sites, the TMF must file site level documents, as specified by Chief Investigator, in TMF site-level file. Only copies of these documents are needed in the TMF site-level file, the original must be kept at site


TRIAL MASTER FILE TABLE OF CONTENTS INVESTIGATOR SITE FILE TABLE OF CONTENTS DESCRIPTION OF DOCUMENTS AND FILING

INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS 0. Table of Contents Table of Contents

File Note Log

0 Table of Contents Table of Contents File Note Log

This table of contents can be modified according to study need. A copy of the Table of contents used for the study must be filed in this section. The File Note Log serves the purpose of tracking File Notes that have been generated for the study.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS 1. Correspondence

Correspondence with CI / Sponsor and internal site correspondence, including Newsletters and other study specific correspondence. Contact Comment Forms Meeting Agendas and Minutes CI site monitoring Correspondence At TMF Site Level File: Monitoring Confirmation and Follow up correspondence

1. Correspondence

Correspondence with CI / Sponsor and internal site correspondence, including Newsletters and other study specific correspondence. Contact Comment Forms Meeting Agendas and Minutes Monitoring Confirmation and Follow up correspondence

See General Guidance



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS 2. Protocol /

Protocol Amendments

Current Protocol Superseded Protocol(s) At TMF site level file: Signed protocol signature page - If applicable, local version and approval of translated version

2. Protocol / Protocol Amendments

Current Protocol (with signature page signed by PI) Superseded Protocols (with signature page signed by PI) If applicable, local version and approval of translated version

See General Guidance

3 Ethics Committee (SAE reporting documentation in section 11)

NRES Application Letter of Favourable Opinion (listing documents approved and

3 Ethics Committee (SAE reporting documentation in section 11)

NRES Site Specific Assessment Application Letter of Favourable Opinion (confirmation of site specific approval)

This section is for all documents pertinent to the Ethics committee, including but not limited to the documents listed. However SAE reporting documentation should be filed in section 11.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS approved participating sites) Submission / Notification and EC acknowledgement /opinion of Amendment GCP Compliance / REC Constitution /Composition / List of members Annual Reports Notice to REC of trial completion EC Correspondence At TMF site level file: First approval and approval of

Acknowledgement / EC opinion of Amendment GCP Compliance / REC Constitution /Composition / List of members Annual Reports Notice to REC of trial completion EC Correspondence

Significant correspondence with the Ethics Committee, including but not limited to, Covering letters, acknowledgement letters and EC opinion must be filed in this section. Note GCP Compliance statement and REC composition / Constitution may not be a separate document and maybe included in the Letter of Favourable Opinion.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS amendments reqd

4. Competent Authority (SAE reporting documentation in section 11)

Clinical Trial Authorisation (CTA) application (paper copy and electronic copy) CTA acceptance letter Submission / Acknowledgement of amendment letters (Paper copy and electronic copy) Annual Reports Notice to MHRA of trial completion MHRA Correspondence At TMF site level file:

4. Competent Authority (SAE reporting documentation in section 11)

CTA acceptance letter Acknowledgement of amendment letters Annual Reports Notice to MHRA of trial completion MHRA Correspondence

This section is for all documents pertinent to Competent Authority (UK – MHRA), including but not limited to the documents listed. However SAE reporting documentation should be filed in section 11. Paper copy of documents submitted for CTA and subsequent amendments must be filed in the TMF. Electronic copy of documents can also be saved onto a disk to keep in the TMF. Significant correspondence with the Regulatory Authority, including but not limited to covering letter, notification letter,



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS First acceptance and acknowledgement letters for amendments

acceptance letter, must be filed in this section.

5. R & D (SAE reporting documentation in section 11)

R & D application R & D approval Annual Reports R & D Notification of trial completion R&D Correspondence At TMF site level file: First R&D approvals and Notification of amendments

5. R & D (SAE reporting documentation in section 11)

R & D application R & D approval R & D Notification / Approval of amendments Annual Reports R & D Notification of trial completion R&D Correspondence

This section is for all documents pertinent local R&D, including but not limited to the documents listed. However SAE reporting documentation should be filed in section 11. Significant correspondence with the R&D Committee must be filed in this section.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS 6. Financial / Legal

Contracts / Contract Addendums with Sub-contractors Confirmation of Sponsorship Funding Letter(s) Financial Agreement Insurance and Indemnity Statement Clinical Trial Agreement Financial Correspondence Declaration of Helsinki

6. Financial / Legal

Contracts / Contract Addendums Funding Letter(s) Financial Agreement Insurance and Indemnity Statement Clinical Trial Agreement Financial Correspondence Declaration of Helsinki

This section is for all documents pertinent to the financial and legal aspect of the study, including but not limited to the documents listed. Insurance and Indemnity Statement must cover entire the period of the study. Declaration of Helsinki only required if not present in the protocol.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS At TMF site level file: Contracts / Contract Addendums Insurance and Indemnity Statement Clinical Trial Agreement

7. Study Site Staff

Template of Delegation of duties and authorised signatures forms Template of study specific CV if applicable Training Material, e.g. Investigator

7. Study Site Staff

Completed delegation of duties and authorised signatures form CVs Trial Training Material and documentation:- - GCP Training

This section is for documents pertinent to site staff education, experience and training. The Delegation of duties and authorised signatures form must be signed by all individuals that perform trial related procedures. CVs are required for personnel that have significant role in the trial. The CV must be



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS meeting agenda and minutes At TMF site level file: Copies of completed delegation of duties and authorised signatures forms, original CV for PI, and CVs for other site staff Trial Training documentation:- - GCP Training - Pharmacovigilance Training - Protocol-related training / Investigator Meeting Documentation If IND study: FDA1572 forms and Financial Disclosures

- Pharmacovigilance Training - Protocol-related training / Investigator Meeting Documentation If IND study, FDA1572s and Financial Disclosures

personally signed and dated by the individual and updated annually. If IND study, investigators listed on the FDA form 1572 must provide CV and Financial Disclosures. If filed separately, training material must be documented in a file note. Training documentation may be in the form of Training Attendance log or certificate.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS

8. Study Related Supplies

Sample CRF Data Management / Data Processing document If applicable: Sample Diary Cards (Translated templates) Sample Questionnaires (Translated templates) Supplies Re-order form templates

8. Study Related Supplies

Sample CRF Data Management / Data Processing document If applicable: Diary Cards (Local versions) Questionnaires (Local versions) Completed order forms / shipping records

This section is applicable for templates of clinical trial materials provided for data recording, examples of these are: Blank Case Report Form, Questionnaires, and Diary Cards. If the CRF is too bulky to keep with the file, it is acceptable to file this separately and document the location in a File Note. (File note applicable if filed separately from Investigator Site File).

9. Participant Information and Consent

Template of all Participant Information Sheets and Informed Consent Forms

9. Participant Information and Consent

Sample of local versions of all Participant Information Sheets and Informed Consent Forms, GP letter

This section is for documents pertinent to subjects’ participation in the study. At time of consenting, participant and consenter must sign 3 copies of the consent form: one given to



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS If applicable: Template of translated Participant Information Sheets and Informed Consent Forms Template and translated templates of GP letter and other Advertisement materials, e.g. Referral packs At TMF site level file: Sample of Participant Information Sheets and Informed Consent Forms (local version)

Signed Participant Information Sheets and Informed Consent Forms If applicable: GP letter and other Advertisement materials, e.g. Referral packs (Local Versions)

the participant, one to the Investigator Site File, one to the participant’s medical notes. Participant must be re-consented if newer version of Participant Information Sheet and Informed Consent Form is available. All versions of ICFs signed by participants must be retained.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS

10. Subject Information

Template Subject ID Form (Confidential Patient ID form) Template Subject recruitment / screening Log Protocol Variance Tracker (for Protocol Deviations / Violations) At TMF site level file: Subject recruitment /screening Log

10. Subject Information

Completed subject ID Form (Confidential Patient ID form) Subject recruitment / screening Log Protocol Variance Tracker (for Protocol Deviations / Violations) Completed CRFs Resolved Data Queries / Data Clarification Form

This section is for documents pertinent to subject information. All documents filed in this section must not disclose the subjects’ identity. (With the exception of the Subject ID form filed in the Investigator Site File) Subjects’ initials and study number may be used. The Protocol Variance Tracker can be set up as one document that can be filed in the TMF if study has a small number of sites or if the study is a multi-centre study, it can be sent up per site and filed in the TMF site level file. If the CRF is too bulky to keep with the file, it is acceptable to file this separately and document the location in a File Note.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS Resolved data queries can be filed with the patient’s completed CRF (File note applicable if filed separately from Investigator Site File).

11 Pharmacovigilance SAE reporting Guidelines and Pharmacovigilance contact Pharmacovigilance Training handout Current SAE form template and superseded SAE form templates SAE / SUSAR reports and associated correspondence

11 Pharmacovigilance SAE reporting Guidelines and Pharmacovigilance contact Pharmacovigilance Training handout Current SAE form template Completed SAE / SUSAR reports and associated correspondence

This section is for documents and correspondence pertinent to the reporting of all SAE/SUSARs. Documents included but not limited to list. Correspondence includes correspondence from PI to CI / EC / Competent Authority & the other applicable Authorities, e.g. Research & Development.

12. Monitoring Minutes from Initiation/ Pre Study Meeting

12. Monitoring Minutes from Initiation/ Pre Study Meeting

This section is for documents pertinent to Monitoring of the trial, including



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS Monitoring log / documentation (e.g. Monitoring visit report)

Monitoring log / documentation

monitoring log and documentations.

13. Clinical Laboratory Central Laboratories Certificates of Accreditation Central Laboratories Normal Reference Ranges (including revisions) Sample Labels Lab Manual Sample Shipment Receipt / Tracking At TMF site level file:

13. Clinical Laboratory Certificates of accreditation for central laboratories and local laboratories Normal Reference Ranges (including revisions) for central laboratories and local laboratories Labels Lab Manual Sample Shipment Record

Certificates of accreditation for central laboratories and local laboratories must cover the entire period of the study. Normal Reference Ranges for central laboratories and local laboratories must be valid during the period of the study and applicable to the patient group (indication / demographic) covering all tests required by the protocol.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS Certificates of accreditation and normal Reference Ranges for local labs of all participating sites

14. Pharmacy Investigational Medicinal Product packaging (label specification, copies of labels) Instructions for handling trial medication and trial related materials (Randomisation, Re-supply, Return / Destruction, Code breaking, IVRS if applicable) Template of Accountability forms / Inventory Forms /

14. Pharmacy Investigational Medicinal Product packaging (label specification, copies of labels) Instructions for handling trial medication and trial related materials (Randomisation, Re-supply, Return/Destruction, Code breaking, IVRS if applicable) Site Investigational Medicinal product(s) accountability

Pharmacy documents if filed separately from the Investigator Site File, i.e. in Pharmacy, must be documented in a file note.



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS Dispensing logs / Temperature logs Study Investigational Medicinal Product Accountability Documentation of Investigational Medicinal product destruction The following is applicable when Pharmacy is involved with Investigational Medicinal Product Manufacturing: - GMP certificate - Certificate of Analysis - Authorisation of release by Qualified Person

(Forms and Shipping Records) Storage Condition Records Documentation of Investigational Medicinal product destruction at site

15.

Investigator’s Brochure / SmPC

IB / SmPC

15. Investigator’s Brochure / SmPC

IB / SmPC

Current and superseded versions of Investigator’s Brochure must be filed in



INSTRUCTIONS SECTION TITLE DOCUMENTS SECTION TITLE DOCUMENTS and Safety alert updates

Safety alert updates

and Safety alert updates

Safety alert updates

this section. Investigator’s Brochure must be updated annually and if update is not required, a file note must document this.

16. Final report

16. Final report

Final report will be produced by CI and submitted to EC at the end of the study.

17. Clinical study report

17. Clinical study report

Clinical study report will be produced by CI upon analysis of data at the end of the study.

* Local versions must be on Institution letter headed paper.

Appendix 2

Study Archiving Checklist Study Title EUDRACT Numbe

Document Present Comments Signature/Date Protocol Protocol Amendments Ethics Documents Informed Consent Forms Patient Information Sheet Contraception Declarations Advertisements Expenses/Payments E-mails / Communications/Letters/TelephoneLogs

Protocol Deviation Records Adverse Event Documentation Monitoring Reports Meeting Notes/Minutes Sponsor Signed Agreements Sponsor Financial Agreements Insurance Certificates Case Report Forms MHRA Approval CTA Authorisation Investigator Brochure Screening Log Randomisation Log Drug Accountability Logs CV’s Delegation Log Signature Log Normal Lab Values Lab Accreditation Equipment Calibration and Maintenance Records

Safety Certificates IMP Sample Labels Shipping Records Certificates of Analysis Temperature Logs Document Tracking Logs Unblinding Documentation Sample Storage Documentation Freezer Logs SOP’s Pharmacy Site file Final Report Data Storage Discs

27

Appendix 3

Northumberland, Tyne and Wear NHS Foundation Trust

Archive Facility Information

Internal - R&D Archive Room

• Within the R&D Department at St Nicholas Hospital, there is a secure, locked storage room with limited access

• Documents, once received for archive, will be stored within the R&D storage room for 12 months before being sent to the Trusts external secondary storage facility. This is to cover a time period where research teams may need access to the documentation and to limit the costly need for retrieval from secondary storage

• Only the Research Governance Facilitator and the Senior Manager for Research, Innovation and Clinical Effectiveness will have direct access to the archived files whilst stored on site

• Once the 12 month period is up, the files will be appropriately boxed and transferred for external storage.

External – NTW Secondary Storage Facility

• The NTW secondary storage facility has been checked and approved by a senior member of the Trust’s team and deemed to be appropriate for the needs of the Trust

• The facility provides secure storage compatible with the required archive needs of the R&D department

28

Appendix 4

Archive Register Fields

• Study title

• Research Ethics Committee (REC) number

• NTW reference number

• Sponsor

• Chief Investigator (CI) / Principle Investigator (PI)

• Date archived/deposit date

• Archive location (R&D/Trust secondary storage provider)

• Duration of the archive

• Date of destruction (if applicable)

• Number of boxes

• Contents

• Archive log completed (Yes/No)

• Activity log – for retrieval

• Named persons for access

• Destruction certificate (certificate and associated paperwork to be retained for 5 years)

29

Appendix 5

R&D Archive Procedure

• Arrangements for archive agreed at CTA stage

• R&D and study team hold study close out meeting

• Study team prepares files for archive

• R&D conduct pre archive audit

• Study team transfer paperwork to R&D

• Chain of custody document started

• R&D store the paperwork for 12 months in the internal archive room

• R&D request box(es) from the records department (after the 12 month period)

• The records department supply the box(es)

• R&D transfer the archive files to the box(es) and create a full contents list.

Box(es) appropriately labelled and all details entered onto the archive log

• R&D transfer box(es) to the records department – completing the chain of

custody document. R&D supply an electronic record of the box contents list

• The records department arrange for the box(es) to be collected by the

secondary storage provider

• The secondary storage provider collect the box(es) from the records

department – completing the chain of custody documents

• The secondary storage provider store the box(es) until required for retrieval or

until the specified date of destruction

30

Appendix 6

Archive Box label • Study Title:

• Trial Site number:

• Eudract Number:

• Chief / Principal investigator:

• Box No:

• Contact Name:

• Contact No:

• Type of Records: CLINICAL RESEARCH DATA

• Date Archived:

• Destruction Date

31

Appendix 7 NTW Archive Chain of Custody Example

Study title: REC Ref: NTW Ref: Date/Time From To Reason Date:

Name/Organisation Name/Organisation

Time:

Signature Signature

Date:


Time:

Signature Signature

Date:


Time:

Signature Signature

Date:


Time:

Signature Signature