SOP02V3 SOP for establishing and maintaining a TMF - Accord

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/2008STANDARD OPERATING PROCEDURE FOR ESTABLISHINGAND MAINTAINING A TRIAL MASTER FILESOP NUMBER:ACCORD/ECTU/SOP02/3.0VERSION NUMBER: 3.0PREVIOUS VERSIONS: 1.0, 2.0EFFECTIVE DATE: 27/10/2008REVIEW DATE: 26/10/2010AUTHOR:Fiona Sloan (Clinical Trials Monitor)APPROVED BY (1):.....Tina.McLelland...................................(R&D Governance Manager, NHS Lothian)DATE APPROVED: 24/10/2008APPROVED BY (2):..... Anne.Langston................................(Associate Director, ECTU, University of Edinburgh)DATE APPROVED: 23/10/2008RELEASED BY:.....Alex.MacLellan........................................(QA Manager, ECMC, University of Edinburgh)DATE RELEASED: 24/10/2008Controlled Document – Do Not CopyPage 1 of 8

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/2008DOCUMENT HISTORYVersion Edited by (job title):Number:3.0 Alex MacLellan (QAManager)2.0 Fiona Sloan (ClinicalTrials Monitor)1.0 Fiona Sloan (ClinicalTrials Monitor)Effective Details of editions made:Date:Format changes as per SOP01,minor text changes.04/02/2008 ACCORD/ECTU SOPreferences updated19/04/2007 New1. PURPOSETo describe the procedure for establishing and maintaining a Trial Master File (TMF).2. APPLICABILITYApplies to the individuals within the ACCORD office responsible for establishing andmaintaining a TMF.The primary focus of this SOP is with Clinical Trials of Investigational MedicinalProducts (CTIMPs) that fall under the Medicines for Human Use (Clinical Trials)Regulations 2004. However, this SOP is also relevant for any project which has tomeet Research Governance Framework standards and any other clinicalinvestigations which may have an impact on the safety and well-being of humanparticipants.3. POLICYThe TMF will contain all the essential documents relating to the clinical trial and willbe stored in a secure but accessible manner. Essential documents are defined inregulatory guidelines as “those documents which individually and collectively permitevaluation of the conduct of the trial and the quality of the data produced. Thesedocuments serve to demonstrate the compliance of the investigator, sponsor, andmonitor with the standards of GCP and with all applicable regulatory requirements”.4. PROCEDURE4.1 ESTABLISHING A TMF4.1.1 The ACCORD Clinical Trial Monitor is responsible for establishing the TMF.4.1.2 The TMF should be established at the beginning of the trial, prior to patientrecruitment.4.1.3 The TMFs will be stored in a lockable cabinet in the Edinburgh Clinical TrialsUnit (ECTU) and will be kept separate from other research files.4.1.4 All essential documents should be legible and accurate.Controlled Document – Do Not CopyPage 2 of 8

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/20084.1.5 The documents that should be included in the TMF are listed in the TMFchecklist for CTIMPs and TMF checklist for non-CTIMPs (attachments 1 and2 respectively). These checklists should be used as a guide only as not alldocuments listed may be applicable for all trials. The appropriatedocumentation will vary according to the nature of the trial (e.g. for CTIMPs,most essential documents must be maintained for legal reasons whereassome documents will not be applicable for non-CTIMPs).4.1.6 Where documents are not applicable this must be documented in a file noteto clearly explain the reasons why the document will not appear in the TMF.4.1.7 Where documents are located elsewhere this must be documented in a filenote to clearly explain the reasons why the document will not appear in theTMF and where this document can be found.4.2 MAINTAINING A TMF4.2.1 The ACCORD Clinical Trial Monitor is responsible for updating the TMF withany relevant new documentation as the trial progresses.4.2.2 All filing should be done in a timely manner, to assist in the successfulmanagement of the study and to allow auditors to access the documentationat any time.4.2.3 Once the trial has finished, the Clinical Trials Monitor is responsible forreviewing the TMF to ensure that all the required documents are present inthe TMF.4.2.4 The documents contained in the TMF must be maintained for at least 5 yearsafter the completion of the trial, unless stated otherwise by the funder. Duringthis time these documents must be easily accessible to the licensing authorityon request. Refer to ACCORD/ECTU SOP13 (SOP for archiving clinicalresearch data) for further guidance.5. ATTACHMENTS1. TMF checklist (CTIMPs)2. TMF checklist (non-CTIMPs)6. RELEVANT DOCUMENTS1. ACCORD/ECTU SOP13 “SOP for archiving clinical research data”.7. DEFINITIONSACCORDECTUAcademic and Clinical Central Office for Research and Development.The ACCORD office is a collaboration between NHS Lothian and TheUniversity of Edinburgh to form a joint research and developmentoffice to facilitate clinical research.Edinburgh Clinical Trials UnitControlled Document – Do Not CopyPage 3 of 8

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/2008TMFA TMF is a standard filing system which allows effective storage andlocation of essential documents. The filing system can be in the formof single project file or a number of files/filing cabinets, depending onwhat is deemed most appropriate.8. REFERENCESICH Harmonised Tripartite Guideline for Good Clinical Practice, CPMP/ICH/135/95.The Medicines for Human Use (Clinical Trials) Regulations 2004, (SI 2004 No. 1031).The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006, (SI2006 No. 1928).Good Clinical Laboratory Practice (GCLP), BARQA 2003.Declaration of Helsinki, Clarification of 5 th Revision, 2004.Controlled Document – Do Not CopyPage 4 of 8

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/2008ATTACHMENT 1TRIAL MASTER FILE CHECKLIST (CTIMPs)(This checklist should be used as a guide only. All documents listed belowmay not necessarily be applicable to all trials. Where documents are missing afile note should be included to document the reasons for this).SectionDetails1 Protocol and Patient Information• Current protocol, signed and dated by the Investigator• Previous protocol amendments• Current PIL and consent form• Previous amended PIL and consent forms• Examples of any other written information provided to patients• Copy of advertisement for patient recruitment• Copy of any letter/information for a patient’s GP or Consultant2 Ethics• Ethics application form for current protocol• Ethics approval for current protocol• Ethics application for previous protocol amendments• Ethics approval for previous protocol amendments• EC attendees where study was approved• Ethics reports• Ethics correspondence3 Research and Development• SSI form• R&D approval letter• Insurance statement• Sponsorship Letter• Signed RGF certificate• Copy of any signed agreements between involved parties• Copy of sponsor agreement and allocation of responsibilities• R&D correspondenceFunding:• Copy of financial information (funding application/awardletter/R&D costings)4 Regulatory• Regulatory application form (and any amendments)• Regulatory approval (and any amendments)• Copy of DDX to CTA transfer letter (if applicable)• Copy of end of trial notification sent to the MHRA5 Safety• Unblinding procedure for blinded trials• Copies of broken blinds (at the end of the trial)Controlled Document – Do Not CopyPage 5 of 8

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/2008• Blank AE/SAE/SUSAR forms (if not in protocol)• Reporting arrangements for SAE/SUSARs (if not already in theprotocol)• Copies of completed SAE/SUSAR forms• Copies of correspondence re SAE/SUSARs from Investigator toSponsor and/or Regulatory Authority• Copies of safety information sent to other Investigators (ifmulticentre trial)• Annual safety reports6 Research Team – Staff and Training• Signed/dated CV of Investigators, Sub-Investigators, Pharmacypersonnel• Delegation log• Signature sheet7 Monitoring and Audit• Risk assessment and monitoring plan• Monitoring reports• Monitoring correspondence (including telephone reports, followupletters etc)• Audit certificate• Clinical trial report8 Investigational Medicinal Product (IMP)• Investigator Brochure (IB) and/or Summary of ProductCharacteristicsLaboratories• Accreditation of all labs used (and updates)• Normal value references for all labs used (and updates)Case Report Forms• Sample copy of CRF (and any previous versions) if not already inthe protocol• Completed CRFs and any corrections• Record of biological samples taken9 Pharmacy (can be stored in pharmacy)• Certificate of analysis of investigational product(s) shipped• Sample labels• Instructions for handling the IMP (if not already in the IB orSmPC)• Drug delivery/return records• IMP accountability logs• Documentation of IMP destruction10 General correspondenceOtherControlled Document – Do Not CopyPage 6 of 8

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/2008ATTACHMENT 2TRIAL MASTER FILE CHECKLIST (non-CTIMPs)(This checklist should be used as a guide only. All documents listed belowmay not necessarily be applicable to all studies. Where documents aremissing a file note should be included to document the reasons for this).SectionDetails1 Protocol and Patient Information• Current protocol, signed and dated by the Investigator• Previous protocol amendments• Current PIL and consent form• Previous amended PIL and consent forms• Examples of any other written information provided to patients• Copy of advertisement for patient recruitment• Copy of any letter/information for a patient’s GP or Consultant2 Ethics• Ethics application form for current protocol• Ethics approval for current protocol• Ethics application for previous protocol amendments• Ethics approval for previous protocol amendments• EC composition where study was approved• Ethics reports• Ethics correspondence3 Research and Development• R&D application form• R&D approval letter• Insurance statement• Sponsorship Letter• Signed RGF certificate• Copy of any signed agreements between involved parties• Copy of sponsor agreement and allocation of responsibilities(only if multi-centre study)• R&D correspondenceFunding:• Copy of financial information (funding application/awardletter/R&D costings)4 Safety• Blank AE/SAE (if not in protocol)• Reporting arrangements for SAEs (if not already in the protocol)• Copies of completed SAE forms• Copies of correspondence re SAE from Investigator to Sponsorand/or EthicsControlled Document – Do Not CopyPage 7 of 8

ACCORD/ECTUSOP Number: ACCORD/ECTU/SOP02/3.0NHS Lothian and Version: 3.0The University of Edinburgh Effective Date: 27/10/20085 Research Team – Staff and Training• Signed/dated CV of Investigators, Sub-Investigators, Pharmacypersonnel• Delegation log6 Monitoring and Audit• Risk assessment and monitoring plan• Monitoring reports• Monitoring correspondence (including telephone reports, followupletters etc)• Trial initiation monitoring visit (if applicable)• Consent Log• Final close-out monitoring visit report• Audit certificate• Clinical trial report7 Laboratories• Accreditation of all labs used (and updates)• Normal value references for all labs used (and updates)8 OtherCase Report Forms• Sample copy of CRF (and any previous versions) if not already inthe protocolGeneral correspondenceControlled Document – Do Not CopyPage 8 of 8