1. The purpose of the Pharmacy Site File To enable the designated trust pharmacy to fulfil its role and exercise appropriate control over all aspects of study medication handling, an accurately maintained Pharmacy Site File containing the essential documents for the sponsored study medication must be kept in the pharmacy. In accordance to the ICH harmonised tripartite guideline for Good Clinical Practice (ICH GCP) states that the essential documents to be filed are those that: Permit the evaluation of the conduct of a trial and the quality of the data produced; When filed in an appropriate and timely manner, greatly assist in the successful management of a trial; Are usually audited by the sponsors independent audit function and inspected by regulatory authorities as part of the process to confirm the validity of the trial conduct and data collection. The purpose of this Standard Operating Procedure is to describe the standard procedures to be followed when preparing and updating the Pharmacy Site File for the ACTIONS trial. 2. Responsibilities with regard to the Pharmacy Site File See Standard Operating Procedure ACTIONS/SOP/004 for guidance on the delegation of duties in pharmacy. The Pharmacy Site File must be set-up and up-to-date prior to the site opening to recruitment. This will be checked at the Site Initiation Visit. 3. Procedures 3.1 Preparation of the Pharmacy Site File The Pharmacy Site File for the trial should be set up in a lever arch file. The labels in Template 1 of this document should be printed, cut to size and affixed to the spine of the lever arch file. The Pharmacy Site File should be stored securely but in a location where only designated members of the pharmacy team have access to the file to complete any delegated duties, refer to the study Standard Operating Procedures or other information held in the File. Appendix 1 contains a Table of Contents for the Pharmacy Site File, which should be followed exactly. 3.2. Maintenance of Pharmacy Site File There must be a complete audit trail of all activity undertaken by pharmacy, sufficient to allow the trial to be recreated from the paperwork, and the paperwork should be ready for monitoring or inspection at any time. Events or decisions not otherwise provided for in the study documents should be recorded in dated and signed File Notes (ACTIONS/DOC/010). Particular care should be taken to ensure that amendment notifications are properly filed on receipt, so that all staff are always working from the correct, up-to-date, versions of the protocol or other documents. Corrections should be made by drawing a single line through the incorrect item; dating and initialling the correction. Tippex correction fluid or other related products should not be used. The original document on which the data was initially recorded must always be retained as it is considered source data. Therefore, where documents contain data that is later transcribed elsewhere, the original must be filed with the later version. ACTIONS/PSOP/001 Version 1.0 Page 2 of 6
3.3 End of study and archive The end of the study is defined in the protocol as the date of the last visit of the last participant, and those actions required at this time are detailed below. Within 90 days of the trial ending, the Chief Investigator will notify all participating sites and site personnel (including pharmacy) that the trial has ended. A member of the ACTIONS coordinating centre will arrange to visit each study site for a close-out visit at this stage to ensuring that all activities relating to the ACTIONS trial have been appropriately reconciled. Close-out is integral to the quality of a trial and is designed to ensure that all necessary documents are in place should the trial data need to be queried or inspected in the future. A close-out visit includes ensuring: All essential documentation for the site are confirmed in the appropriate files, providing a clear audit trail of study conduct at the site All site data is collected, entered, validated and all data queries resolved where feasible. This includes queries resulting from reconciliation of the database All issues from previous study monitoring procedures are resolved and documented All financial matters are resolved and all site payments are complete as agreed and documented in study contracts/agreements/approvals Final drug accountability is complete and destruction of unused study drug is documented in the site file The Principal Investigator is aware of and, where appropriate, has implemented relevant ongoing requirements such as site archiving, subsequent audit/inspection procedures and any ongoing reporting requirements Files are confidential Once the above criteria are met, the site is considered closed and a Confirmation of Site Closedown Letter will be sent to the Principal Investigator. At a local site, the Principal Investigator should undertake archiving arrangements in conjunction with the Chief Investigator and in accordance with local policy and guidelines. Once archiving is requested by the coordinating centre, the Principal Investigator should contact pharmacy to request that all documents and files, including the Pharmacy Site File are transferred to the local study office for archiving. The process of archiving is covered in more detail in the Standard Operating Procedure ACTIONS/SOP/019. 4. Relevant SOPs and Related Documents 4.1 Relevant SOPs ACTIONS/SOP/004 Delegation of Duties and Study Personnel Documentation ACTIONS/SOP/019 Study Close Down and Archiving 4.2 Related Documents ACTIONS/DOC/010 File Note ACTIONS/PSOP/001 Version 1.0 Page 3 of 6
Appendix 1: Table of Contents for the Pharmacy Site File Table of Contents References Site File Index Coordinating Centre and Chief Investigator Contact Details Contact details for Principal Investigator and other study staff (Copy to be sent to coordinating centre with every update) 1.0 Standard Operating Procedures and Documents 1.1 Delegation of Duties and Study Personnel Documentation ACTIONS/SOP/004 1.2 Site Initiation Visit and Monitoring ACTIONS/SOP/005 1.3 Prescribing and Handling Study Medication ACTIONS/SOP/009 1.4 Pharmacovigilance at Participating Sites ACTIONS/SOP/012 1.5 Study Withdrawal & Unblinding of trial arm allocations ACTIONS/SOP/013 1.6 Deviations and Serious Breaches of GCP or the Trial Protocol ACTIONS/SOP/014 1.7 Amendments ACTIONS/SOP/016 1.8 Study Close Down and Archiving ACTIONS/SOP/019 1.9 Set-up and maintenance of Pharmacy Site File ACTIONS/PSOP/001 1.10 Monitoring Temperature in Pharmacy ACTIONS/PSOP/002 1.11 Ordering, Receiving and Storage of Clinical Trial Supplies ACTIONS/PSOP/003 1.12 Dispensing Study Medication and Handling Returns ACTIONS/PSOP/004 1.13 Suspected Adverse Drug Reactions, Unblinding and Reporting from GCP ACTIONS/PSOP/005 or the Protocol 1.14 Study Medication Recall and Quarantine ACTIONS/PSOP/006 1.15 Destruction of Study Medication ACTIONS/PSOP/007 1.16 Participating Site Contact Details ACTIONS/DOC/001 1.17 Site Delegation and Signature Log ACTIONS/DOC/002 1.18 Research CV Template ACTIONS/DOC/004 1.19 Staff Training Log ACTIONS/DOC/005 1.20 Pharmacy Personnel Pack ACTIONS/DOC/043 1.21 Study Prescription Form ACTIONS/DOC/045 1.22 Pharmacy Delegation Log ACTIONS/PDOC/001 1.23 Temperature Monitoring Log ACTIONS/PDOC/002 1.24 Clinical Trials Supplies Inventory ACTIONS/PDOC/003 1.25 Pharmacy Enrolment Log ACTIONS/PDOC/004 1.26 Clinical Trials Supplies Order Form ACTIONS/PDOC/005 1.27 Medication Accountability Form ACTIONS/PDOC/006 1.28 Catalent Shipment Request Form ACTIONS/PDOC/007 1.29 Trial Drug Recall Summary Sheet ACTIONS/PDOC/008 1.30 Quarantine Notice ACTIONS/PDOC/009 1.31 Quarantine Log ACTIONS/PDOC/010 1.32 Certificate of Destruction ACTIONS/PDOC/011 2.0 Protocol 2.1 Current Protocol 2.2 All superseded versions of the Protocol (if applicable) 2.3 Completed Protocol Deviation Record Sheets and Potential Serious Breach Forms 2.4 Summary Protocol 2.5 Related correspondence 3.0 Pharmacovigilance 3.1 Investigators Brochure 3.2 Related correspondence ACTIONS/PSOP/001 Version 1.0 Page 4 of 6
4.0 Regulatory Approvals Original Application to MHRA & REC 4.1 Ethics approval letter 4.2 Notice of acceptance letter (CTA) 4.3 Amendment Approval Letters 5.0 NHS Permission 5.1 Trust R&D NHS permission letter 5.2 Related correspondence 6.0 Amendments 6.1 Log of all the amendments submitted to MHRA and REC 6.2 Amendment pack(s) 7.0 Sponsor Documents 7.1 Clinical trial site agreement 8.0 Research Team Personnel and Training 8.1 Signed forms from Pharmacy Personnel Pack 8.2 Copy of Site Delegation and Signature Log (from Investigator Site File, including superseded versions) 8.3 Pharmacy Delegation Log 9.0 Trial Arm Allocation Document 9.1 Pharmacy Enrolment Log 10.0 Pharmacy Supplies 10.1 QP Certification 10.2 ACTIONS Clinical Trials Supplies Order Forms, Delivery Notes and copies of the Request for Shipment of Clinical Supplies from Catalent, Bolton 10.3 Clinical Trial Supplies Inventory 11.0 Participant Documents 11.1 Completed Study Prescription Forms faxed and original 11.2 Participant Medication Accountability Forms 12.0 Temperature Monitoring 12.1 Temperature Logs 13.0 Recall, Quarantine, and Destruction Documents 13.1 Study Medication Recall Summary Sheet 13.2 Study Medication Quarantine Log 13.3 Study Medication Quarantine Notice 13.4 Clinical Trial Certificate of Destruction 14.0 Monitoring and Audit 14.1 Site Initiation Report 14.2 Site Initiation Visit Log 14.3 Open to recruitment letter 14.4 Monitoring schedule 14.5 Monitoring Summaries, Actions Lists and Log 14.6 Close-out Reports 14.7 Related correspondence 15.0 General Correspondence 15.1 Emails/letters/telephone conversation/investigator meetings 16.0 Documents Held Elsewhere 16.1 Record of study relevant information held elsewhere ACTIONS/PSOP/001 Version 1.0 Page 5 of 6
Template 1: Labels for lever arch files to create Investigator Site File Site: Pharmacy Site File 1 EUdraCT Number 2009-009235-30 HTA Project 07/83/01 Sponsor Number CRO 1250 Site: Pharmacy Site File 2 EUdraCT Number 2009-009235-30 HTA Project 07/83/01 Sponsor Number CRO 1250 Site: Pharmacy Site File 3 EUdraCT Number 2009-009235-30 HTA Project 07/83/01 Sponsor Number CRO 1250 ACTIONS/PSOP/001 Version 1.0 Page 6 of 6