Joint Arrangements for Research __________________________________________________________________________________

STANDARD OPERATING PROCEDURE SOP 305 CREATING AND MAINTAINING A TRIAL MASTER FILE

SOP 305

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Joint Arrangements for Research __________________________________________________________________________________ PROPERTY This Standard Operating Procedure (SOP) is the property of NNUH and UEA Research and Development (R&D) and the information contained herein is propriety and confidential. The distribution, copying or dissemination of this SOP or its contents to non R&D personnel is strictly prohibited without prior written permission of the R&D Departments Printed copies are not controlled and must be destroyed after use. TABLE OF CONTENTS

1 ABBREVIATIONS 2 INTRODUCTION 3 SCOPE 4 RESPONSIBILITY 5 PROCEDURE 6 REFERENCES 7 LIST OF APPENDICES Appendix 1 : Suggested Trial Master File contents Appendix 2: Example of Delegation Log Appendix 3: Change control form and Review sheet

3 3 3 3 4 4 4 5 7 8

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Joint Arrangements for Research __________________________________________________________________________________ 1 ABBREVIATIONS CI CTIMP CRTU GCP ICH NNUH PI SAE SOP TMF UEA 2 Chief Investigator Clinical Trial of an Investigational Medicinal Product Clinical Research and Trials Unit Good Clinical Practice International Conference for Harmonisation Norfolk and Norwich University Hospital Principle Investigator Serious Adverse Event Standard Operating Procedure Trial Master File University of East Anglia

INTRODUCTION

A trial master file (TMF) contains the essential documents relating to a clinical trial. This collection of essential documents serves to demonstrate compliance of the investigator, Sponsor and trial monitor with the standards of Good Clinical Practice which the Trust and UEA adheres to in all its research. This is a legal requirement for trials which fall under the 2001/20/EC Clinical Trials Directive. TMFs may be required for inspection and audit. This SOP is intended as a practical guide to setting up a TMF and the essential documents it should contain. 3 SCOPE

This SOP applies to all research approved within the Research governance systems of the NNUH and UEA. It is a legal requirement for Clinical Trials of Investigational Medical Products (CTIMPs). For studies which do not involve investigational medicinal products the master file contents may be adapted to reflect the nature of the study, however the general principle of establishing a TMF should be adopted as part of adherence to Good Clinical Practice (GCP). The Trust and UEA require TMFs to be in place for all approved research for which the organizations act as Sponsor. Commercial and external sponsors may specify particular formats for trial master files which should be adhered to. 4 RESPONSIBILITY The Clinical Trial Sponsor is responsible for setting up a Trial Master file and ensuring that the local investigator/s set up Investigator site file/s (ISFs) and that these are available for audit and inspection. Although the collective of all the clinical trial documents (those stored with both the trial sponsor and investigator/s) is the Trial Master File, the file of the sponsor is commonly referred to as the Trial Master File and the investigator(s) as the Investigator Site File. In practice the Chief Investigator/Local Site investigator will be responsible for establishing and maintaining the site files and may delegate these activities to their research team

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Joint Arrangements for Research __________________________________________________________________________________ members. If activities are delegated this should be recorded in a delegation log and stored in the file. 5 PROCEDURE 5.1 The TMF should be set up by the CI/PI during the planning stage of the research and before formal approval of the research takes place. 5.2 The site file contents should be established. A list of contents is provided in Appendix 1 5.3 The file should contain an investigator responsibilities/delegation log. An example responsibilities/delegation log form is included in Appendix 2 5.4 The file should be stored in a secure location, such as a lockable filing cabinet or lockable room with restricted access. The CI should be able to demonstrate that all reasonable measures have been taken to ensure its security, to protect confidentiality and data integrity. 5.5 All documents must be version controlled 5.6 All documents must be dated and signed where appropriate. 5.7 All previous versions of documents must be retained 5.8 A file note (dated and signed) should be placed in the file giving details of any missing or unavailable documentation 5.9 On completion of the study the completed file should be archived ( see SOP 900) 6 REFERENCES

Commission Directive (2003/94/EC) of Good Manufacturing Practice Commission Directive (2205/28/EC) on Good Clinical Practice Directive 2001/83/EC The Pharmaceuticals Directive EU Clinical Trials Directive 2001 (2001/20/EC) Medicines for Human Use (Clinical Trials) regulations 2004 (S.I. 2004/1031) Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I.2006/1928) ICH (1996) Guidance for Industry E6 Good Clinical Practice (section 8) 7 LIST OF APPENDICES Appendix 1 Trial Master File Contents Appendix 2 Investigator Responsibilities Delegation log Appendix 3 Change control form and review sheet

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Joint Arrangements for Research __________________________________________________________________________________ Appendix 1: Suggested Trial Master File/Site File Contents. Note: This should be adapted to suit the type of study conducted. Section 1 2 3 4 5 6 7 8 Title Index of file contents Protocol/Amendments Sample CRF/Questionnaires Diary Cards Regulatory Approval/Documentation Investigator responsibility log Curriculum Vitae Patient Identification form Patient recruitment/Screening form Sample of all versions of Patient Information Sheets/Consent Forms/GP letters Completed Patient Information and Informed consent forms Correspondence Current version, Original and any amendments If too much for this section use file note to detail where located. With signatures ( see example in Appendix 2) CV for all personal listed in the investigator responsibility log. Contents/Comments

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Meetings minutes from initiation meetings/steering group meetings. Monitoring logs Notes of telephone calls

File in chronological order. Include emails. Include newsletters If the study is not monitored state this in a file note. Telephone call notes should relate to agreements or significant discussions regarding the trial administration, conduct and SAEs

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Blank copies of serious adverse events (SAEs) forms and instructions for completion Notification of SAEs and/or safety reports By investigator to co-ordinating research body By co-ordinating research body to investigator By co-ordinating research body to regulatory authority. If notifications are

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Joint Arrangements for Research __________________________________________________________________________________ electronic include file note to record this 13 14 Randomisation details Trial medicines : instructions for handling medication and materials Shipping records 15 Clinical Laboratory Reference ranges and accreditation certificates. Contracts Signed copies of contracts and agreements including any financial details, indemnity arrangements, regulatory documents, confidentiality agreements. Any invoices or financial transaction records. If held elsewhere include a file note. If Pharmacy hold these include a file record to state this.

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17

Financial details

18 19 20 21 22

Investigator Brochure Safety Alert letters/Updates Completed Data queries Study training materials Annual progress reports Miscellaneous ( specify) After completion of the trial the following must be filed for archiving.

23 24 25 26

Investigational products accountability at site Documentation of medicinal product destruction Final report Clinical Study report

This will be with Pharmacy

From investigator to REC To document results and interpretation of trial

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Joint Arrangements for Research __________________________________________________________________________________ Appendix 2: Example of Investigator Responsibilities Delegation log

Study Title Principle Investigator Name Responsibilities ( See Key below ) Initials

R&D Reference Site Signature Date of signature Date and Signature of PI Date of leaving

Key 1 2 3 4

To be adapted to suit the study Screening subjects for eligibility Taking informed consent Maintaining regulatory documentation Patient enrolment and follow-up

5 6 7 8 9

Checking eligibility criteria Data collection and entry Reporting SAEs Source document entries ( Medical notes) Data validation

10 11 12 13 14

Taking bloods Sample transport Performing study training Other: Specify Other specify

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Joint Arrangements for Research __________________________________________________________________________________

Appendix 3:

SOP Change Control Form

SOP No: 0000

Version No

Page No

Effective date

Section Change details

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Joint Arrangements for Research __________________________________________________________________________________

REVISION SHEET REVISION HISTORY: Version No Change Date Reason for Change

NAME (PRINT)

SIGNATURE

DATE (DD MM M YYYY )

REVIEWED BY ROLE REVIEWED BY ROLE

ROLE

ROLE

ROLE

ROLE

ROLE

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