Research & Development Directorate

Transcription

1 Research & Development Directorate Type of Document Standard Operating Procedure Name SOP10: Routine Audit Version 3.0 Author Miss Jennifer Boyle (Research Governance Co-ordinator) Version Superseded 2.4 Ratified by UHSM Research and Development SOP Committee Date Ratified 16/12/2011 Dr Andrew Maines (Head of Research and Development) Approved by Signature: Date: 20/12/2011 Date effective from 20/12/2011 Next review date 2 Years from Effective Date Purpose The purpose of this SOP is to inform the reader of the procedures for a routine audit initiated by the Research & Development Department (R&D) at University Hospital of South Manchester NHS Foundation Trust (UHSM). Background ICH Good Clinical Practice (GCP) defines an audit as follows: A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analysed and accurately reported according to the protocol, sponsor s Standard Operating SOP10 Routine Audit (v3.0) Page 1 of 34

2 Procedures (SOPs), Good Clinical Practice (GCP) and the applicable regulatory requirements. (ICH GCP 1.6) Conducting audits of active research studies within the Trust is a vital function of research governance that enables the R&D department to assess the conduct of a research study. The primary objective is to ensure that research participants are protected. Information gained from conducting an audit will identify if the research is being conducted safely and according to the research protocol, GCP standards and relevant legislation. It will also identify if the research team have any training requirements or specific needs. If research is not being conducted according to the research protocol, GCP standards and relevant legislation and research staff are not appropriately trained, then the safety of the research participants may be at risk. In addition to protecting research participants, audits ensure that research staff receive the training and assistance that they need to ensure that research conducted within the Trust continues to be of a high standard. The R&D department will endeavour to provide a supportive and pro-active service to Trust research staff. Responsible Personnel This SOP applies to all staff involved in conducting research at UHSM, however the Principal Investigator (PI) will be the first point of contact when the R&D department initiate a routine audit. The Research Governance Manager (RGM) or Research Governance Co-ordinator (RGC) will be responsible for initiating and conducting a routine audit, and will also be responsible for the follow up of any subsequent actions required by the research team, as a result of the audit. The PI does not have to be available when the audit is conducted, but the RGC/RGM would expect to liaise with a key contact for the research, for example a Research Nurse or Trial Administrator. Procedure A routine audit is an informal and planned process which can take place prior to, during or after the patient recruitment phase. Research projects are selected on a semi random, semi risk-assessed basis for audit. Research projects which are identified as higher risk projects, for example clinical trials of investigational medicinal products (CTIMPs), UHSM sponsored research or research involving vulnerable participant groups, would normally take precedence over relatively lower risk research projects such as questionnaire based research. However, a representative sample of all research undertaken at the Trust is the ideal requirement. To notify a Principal Investigator of a planned audit, the RGM/RGC will issue a standard Notification of Audit letter. This letter will contain the following: Research project details (Title/REC reference/r&d reference) Date of the planned audit A request for the Principal Investigator to the RGC to confirm receipt of the audit notification. A request for a complete list of participants. The list must include all participants in the research study, and consist of each participants study identification number, date of recruitment and randomisation arm where applicable. It is specified in the letter that the list of recruited participants must be submitted to the RGC no later than two weeks prior to the date of the audit. A request for the Trial Master File(s) to be made available on the day of the audit. A request for a desk and chair for the auditor to conduct the audit. SOP10 Routine Audit (v3.0) Page 2 of 34

3 Upon receipt of an from the PI confirming receipt of the notification or audit letter, the RGC will communicate with the PI or designated member of their research team (e.g. research nurse) to arrange a convenient time and location to conduct the audit. If the RGC has not had a response from the PI, the RGC will or telephone the PI or his/her secretary for initial contact. In addition to confirming a time and location for the audit, the RGC will also notify the PI or designated research team member of which participants have been randomly selected for inclusion in the audit, from the list provided. Approximately 10% will be selected. The auditor will require the selected participants medical case notes and case report forms (CRFs) to be available for the audit, along with the Trial Master File and any other specific files containing information and data pertaining to the research project to be audited. The RGC will complete a Monitoring and Audit Joint Inspection Toolkit (MAJIK) form during the audit. A blank copy of the MAJIK form can be viewed in appendix A of this SOP. The RGC will review the Trial Master File, participant case notes, participant CRFs and any other study related documentation provided to complete the MAJIK form. The R&D Project File will also be taken to the audit to cross reference documentation, to ensure that the R&D department have all relevant and up to date versions of the study documentation. All application forms (REC, R&D, MHRA, SSI, Amendments) in the R&D file should be compared with the copy in the Master File to ensure they are the same version. Similarly, dates of all approval letters and dates and version numbers of all recruitment documentation (participant information, consent forms etc) should match. The MAJIK form consists of thirteen sections. A brief overview of these sections is described below: Section 1: Regulatory Approval Section 1 will be used to check that all regulatory application forms and approvals are in place. Regulatory applications and approvals should be retained in the Master File for the initial application and also for post-approval amendments. For example, Research Ethics Committee (REC), Research & Development (R&D), Medicines & Healthcare products Regulatory Agency (MHRA), Ionising Radiation & Medical Exposure Regulations (IRMER) and Administration of Radioactive Substances Advisory Committee (ARSAC). Also, there should be evidence in the Master File that annual progress reports have been completed and sent to the REC / R&D. Section 2: Trial Master File The auditor will check that the Master File has evidence of all application forms, approval letters, delegation log, screening log, recruitment log, relevant signed agreements/contracts and key correspondence. The Master File should also have evidence of research staff training, up-to-date Good Clinical Practice (GCP) training certificates and curriculum vitae s. The auditor will also ensure that any research staff who do not have an employment contract with UHSM have either an Honorary Research Contract or Letter of Access permitting them to work within the Trust. The Master File must also contain original, signed and dated consent forms for all recruited participants. Section 3: Patient Information Sheets, Consent Forms and other study documentation The Master File should have a copy of the current version (and superseded versions) of all study documentation, including the participant information sheet, informed consent form, GP letter, questionnaires, diaries and advertisements. The auditor will check that all documentation has the correct version number, date and contact information on. The auditor will also check that hospital headed paper and the Trust logo are being used. Section 4: Recruitment and Consent SOP10 Routine Audit (v3.0) Page 3 of 34

4 The auditor will look for a screening log and a recruitment/randomisation log and check that these logs are completed and maintained correctly. The auditor will also scrutinise the participant consent forms to check that they have been completed correctly, i.e. signed and dated by the researcher and the participant, the dates of both signatures match, the participant has initialled rather than ticked each box and that the correct version of the consent form has been used. Reference to the delegation log will also be made to make sure that staff who have taken informed consent have the delegated responsibility to do so. Section 5: Pharmacovigilence The auditor will review the Master File and the participant case notes and CRF to verify if all adverse events have been logged and reported correctly. Section 6: Protocol Deviations The auditor will review all documentation to check that any protocol deviations or serious breaches have been logged and reported correctly. Section 7: Source Data Verification Participant medical case notes will be checked with the protocol to ensure that all investigations, treatments and follow-ups required by the protocol have been undertaken. Case notes will also be checked against the CRF to ensure that data entered into the CRF is accurate in terms of results of investigations and dates of occurrences. Reference to the delegation log will also be made to make sure that staff who have performed interventions and completed CRFs have the delegated responsibility to do so. All entries in CRFs should be accurate, legible and timely. Section 8: Data Protection The auditor will speak to a member of the research team about data protection issues. It is important that the auditor is satisfied that all patient identifiable data, CRFs and medical records are kept in locked cabinets within locked offices. There should be limited access to this data. All data stored electronically should be password-protected and there should be limited access to this data. Electronic data should also be stored on Trust or University equipment to ensure that it is protected by authorised back-up and firewall systems. Section 9: Patient Records The auditor will check that there is a copy of the participant information sheet, informed consent form and GP letter in the case notes for each participant. There must also be evidence that the patient has been approached in a timely manner to consider the research, that the eligibility criteria have been considered, that informed consent has taken place and that the participants have been reviewed appropriately. Participant case notes should also have a trial sticker (provided by R&D at the time of approval) on the back inside cover. Section 10: Investigational Medicinal Product The Pharmacovigilence Pharmacist will complete section 10 of the MAJIK form (not necessarily on the same day as the audit) and will check that all Investigational Medicinal Products (IMPs) and Non-Investigational Medicinal Products (NIMPs) are stored, logged, dispensed and destroyed correctly. Section 11: Human Tissue Act The auditor will check to see if samples are being taken and stored in the manner which was approved by the Research Ethics Committee. Where applicable, a local Material Transfer Agreement (MTA) should be in place for samples that will be sent off site. Section 12: Medical Devices The auditor will check that medical devices are used for the purpose described in the research protocol, approved by the Research Ethics Committee. Section 13: Equipment SOP10 Routine Audit (v3.0) Page 4 of 34

5 The auditor will review equipment logs where necessary to ensure that research equipment is appropriately maintained and calibrated. When the audit has been completed, the RGC will write a report to document the findings. This will be done in the R&D department. The audit report should be written as soon as possible after the audit. The audit report should highlight areas of good practice, areas which need attention and recommendations or actions to be taken by the PI. The report should also state which participant records were reviewed. A copy of the audit report and a table of actions required by the PI will be sent to the PI and any key members of his/her research team that have been involved with the audit. If the audit uncovers a serious breach of GCP/Protocol the RGM/RGC are bound by law to inform the REC and MHRA (for drug/device trials). The breach must be likely to affect to a significant degree the safety or mental integrity of the subject, Trial or scientific value of the Trial. The RGC will contact the PI one month after the report has been issued to arrange a follow up visit. At this visit, the RGC will check that the actions detailed in the report have been implemented. If the actions have not been addressed in a timely manner, it may be necessary to suspend recruitment to the research project until the actions are implemented. The RGC would discuss this with the RGM, and if necessary, the Head of Research & Development. If a CTIMP study is suspended the Pharmacy Operational Manager must be notified and if it is sponsored by the Trust, the R&D Sponsor Oversight Committee must be informed. Related Procedures SOP 9 -Project Suspension SOP 14 -Study Files Appendices MAJIK Monitoring and Audit Joint Inspection Toolkit References ICH-GCP Guidelines. Research Governance Framework for Health and Social Care (2 nd Edition 2005). SOP10 Routine Audit (v3.0) Page 5 of 34

6 Manchester Academic Health Science Centre (MAHSC) MAJIK - Monitoring and Audit Joint Inspection Tool Kit Research Governance Monitoring Tool Site Visit Date: Study Title: Chief Investigator/Local PI: Project ID Contact: R&D REC EudraCT number (if applicable): Sponsor: Sections to be completed: Study site(s): Purpose of Audit: Stage of Project Routine: Initiation During For Cause: Closure Auditors: Is this a multi-centre study? MANDATORY QUESTIONS Date of ethical approval and REC approval letter: Is a CTA present? SOP10 Routine Audit (v3.0) Page 6 of 34

7 Date of CTA If a CTA is not necessary is there written evidence that this is the case? Date of R&D approval at this site 1. REGULATORY APPROVAL This section is not to be used in this audit Set-up Ethics Yes Partial No N/A Comments Possible solution and follow up 1.1 Does the REC submission match that held by R&D (including submission codes)? 1.2 Is there a copy of the approved REC application available, with submission codes & signatures?* 1.3 Is a copy of the REC approval letter present?* 1.4 Have all conditions of the REC approval been met? 1.5 Was the REC qualified for the type of study reviewed (e.g. Recognised REC for CTIMP; paediatrician present for paediatric trials)? 1.6 Is the REC composition present?* 1.7 Is a signed SSI form present?* 1.8 Does the SSI form match that held by R&D (including submission codes)? SOP10 Routine Audit (v3.0) Page 7 of 34

8 1.9 If a multi-centre study, is there REC approval for all participating sites?* 1.10 Did the study commence within 12 months of REC approval? MHRA 1.11 Is there a signed copy of the CTA application form?* 1.12 Is a copy of the CTA present?* 1.13 Have any remarks on the CTA been addressed?* 1.14 Does the CTA cover all participating sites (if multi-centre study)? 1.15 Does the CTA cover this site? R&D 1.16 Is this the lead site for this study? 1.17 If the lead site, is there documented approval for all participating sites?* 1.18 Is there evidence of an appropriate named sponsor?* 1.19 Is there a copy of the NHS R&D application?* 1.20 Is the R&D approval for this site present?* 1.21 Is R&D approval the regulatory green light to proceed? 1.22 Is there documented evidence of all checks having been completed prior to R&D approval (including QP, CofA) SOP10 Routine Audit (v3.0) Page 8 of 34

9 1.23 Is there documented evidence of a risk assessment having been completed? 1.24 Have all risks identified in the risk assessment been addressed? 1.25 Are there copies of PI & appropriate site staff CVs?* 1.26 Is there documented evidence of GCP training for site staff in the last 2 years?* 1.27 Do any site staff who are not substantive employees have appropriate honorary contractual arrangements? 1.28 Has the employer of the CI/PI been notified (if not the sponsor) 1.29 Is there documentary evidence of clearly defined roles and responsibilities of sponsor, investigator & participating sites?* 1.30 Is there evidence that the archiving plan has been discussed with the research team prior to regulatory green light? Other Regulatory Approval 1.31 Is there a copy of the ARSAC approval?* 1.32 Is there a copy of the IRMER approval?* 1.33 Is there a copy of the GTAC approval?* 1.34 Is there a copy of the University REC approval? SOP10 Routine Audit (v3.0) Page 9 of 34

10 Post-approval 1.35 Have there been any amendments to the study? 1.36 Is there documentary evidence of the sponsor being consulted as to whether an amendment is substantial or not? 1.37 Is there documented evidence of approval for each amendment from: REC* MHRA* R&D* Sponsor (if not Trust, e.g. University)* 1.38 Have annual progress reports been submitted to the REC?* 1.39 Is there evidence of sponsor oversight of the annual progress report? 1.40 Have annual safety reports been submitted to MHRA?* 1.41 Is there evidence of sponsor oversight of the annual safety report? 1.42 Is there evidence that the Investigator Brochure has been updated annually?* 2. TRIAL MASTER FILE This section is not to be used in this audit Does the TMF contain the following documents? NB: All items marked * should also be present in the Trial Master File 2.1 Currently approved version of the protocol (signed and dated) SOP10 Routine Audit (v3.0) Page 10 of 34

11 2.2 Copies of previous versions of protocol (signed and dated) 2.3 Sponsorship agreement 2.4 Laboratory agreement 2.5 Pharmacy agreement 2.6 IMP supply agreement 2.7 IMP packaging agreement 2.8 Service level agreement for other services 2.9 Financial agreement 2.10 Grant application and letter of award 2.11 Insurance/indemnity statement 2.12 Clinical trial agreement 2.13 Material Transfer Agreement 2.14 Sponsor/investigator roles and responsibilities agreement 2.15 Site agreement/sub-contracts participating sites 2.16 Is the sponsor a named party on all agreements relating to trial activities? 2.17 ARSAC application 2.18 IRMER application 2.19 GTAC application 2.20 Sample case report form 2.21 Laboratory accreditation certificates 2.22 Laboratory reference ranges 2.23 Code break procedure SOP10 Routine Audit (v3.0) Page 11 of 34

12 2.24 Is there documented evidence of a "dummy" code break procedure having been carried out? 2.25 Screening log 2.26 Randomisation log 2.27 Current investigator brochure (including updates) 2.28 Current Summary of Product Characteristics (SmPC) 2.29 Initiation visit report (including who was present) 2.30 Monitoring log and reports 2.31 Communications on key issues 2.32 Delegation log with clear delegation and completed signatures Are the delegated responsibilities clearly defined? Have all delegated duties been delegated by the PI? Has the delegation log been signed and dated by the PI & delegated individual 2.33 Up-to-date training record for every member of the research team Sponsored Multi-centre Studies 2.34 Documented participating site feasibility assessment? 2.35 Participating site initiation communications? 2.36 Evidence of training of site staff in participating sites? SOP10 Routine Audit (v3.0) Page 12 of 34

13 3. PATIENT INFORMATION SHEETS, CONSENT FORMS & OTHER STUDY DOCUMENTATION This section is not to be used in this audit Patient Information Sheets 3.1 Is the currently used patient information sheet approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.2 Are copies of any previously used patient information sheets present?* 3.3 Were these approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.4 Is Trust headed paper being used? 3.5 Is out of hours contact information provided to patients? 3.6 Has this telephone number been tested (by whom & when)? Consent Forms 3.7 Is the currently used consent form approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.8 Are copies of any previously used consent forms present?* SOP10 Routine Audit (v3.0) Page 13 of 34

14 3.9 Were these approved for use by REC* R&D* Sponsor (If not NHS Trust)* 3.10 Is Trust headed paper being used? 3.11 Does the consent form permit access to casenotes and data for audit purposes? 3.12 Does the consent form specify the date and version number of the Patient Information Sheet? Other study documentation 3.13 If a GP information letter is being used, is this approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.14 If a consultant letter is being used, is this approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.15 If an advertisement is being used, is this approved for use by REC* R&D* Sponsor (if not NHS Trust)* SOP10 Routine Audit (v3.0) Page 14 of 34

15 3.16 If a letter of invitation to participants is being used, is this approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.17 If a patient card is being used, is this approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.18 If a patient diary is being used, is this approved for use by REC* R&D* Sponsor (if not NHS Trust)* 3.19 If a questionnaire is being used, is this approved for use by REC* R&D* Sponsor (if not NHS Trust)* 4. PATIENT RECRUITMENT & CONSENT This section is not to be used in this audit 4.1 How many patients at this site have been screened consented enrolled withdrawn SOP10 Routine Audit (v3.0) Page 15 of 34

16 4.2 Is the screening & enrolment log present?* 4.3 Is the screening & enrolment log being appropriately maintained? 4.4 Is there a consent form present for every patient on the participation log? 4.5 Are all original signed consent forms filed in the site file?* 4.6 Has the patient initialled (rather than ticked) all the boxes on the consent form? 4.7 Has the consent form been signed and dated by the subject? 4.8 Has the consent form been signed and dated by the person taking consent? 4.9 Do the dates of the signature of the participant and the person taking consent match? 4.10 Does the person taking consent have delegated authority to do so according to the delegation log? 4.11 Is consideration of the inclusion/exclusion criteria documented in the casenotes? 4.12 Is there evidence of oversight of this by a medically qualified person? SOP10 Routine Audit (v3.0) Page 16 of 34

17 4.13 Is the approach to the participant & provision of patient information documented in the casenotes? 4.14 Was the correct version of the patient information sheet provided to the patient? 4.15 Is the consent process documented in the casenotes? 4.16 Has adequate time for the patient to consider participation been given? 4.17 Has consent been obtained prior to any study procedures taking place? 4.18 Have any specific procedures prescribed by the protocol/rec been adhered to? 4.19 Have appropriate measures been taken for a paediatric setting? 4.20 Have appropriate measures been taken for studies involving vulnerable adults? 4.21 If the protocol has been amended, has re-consenting been undertaken and documented appropriately? 4.22 Is it possible to fully reconstruct the consent process from the documentation available? 5. PHARMACOVIGILANCE & ADVERSE EVENT REPORTING This section is not to be used in this audit SOP10 Routine Audit (v3.0) Page 17 of 34

18 5.1 Is there a documented system for the following in relation to serious adverse events? Identifying Assessing Recording Reporting 5.2 Have any SAEs/SUSARs been identifed in this trial? 5.3 Is there a log of Adverse Events? 5.4 Is the Adverse Event log being appropriately maintained? 5.5 Have any SAEs/SUSARs been identified, assessed for causality, recorded and reported as required by MHRA* REC* Sponsor* Local Trust R&D* 5.6 Have any SAEs/SUSARs been assessed for causality by a medically qualified person? 5.7 Have any SAEs/SUSARs been assessed for expectedness by a medically qualified person? 5.8 Is the person conducting assessment for causality and expectedness permitted to undertake this role in accordance with the delegation log? SOP10 Routine Audit (v3.0) Page 18 of 34

19 5.9 Have AEs/SAEs/SUSARs been reported within the required timescales? 5.10 Is there evidence that the sponsor has been notified of all AEs/SAEs? 5.11 Are reported SAEs/SUSARs verifiable against patient records? 5.12 Have SAEs/SUSARs been followed up to conclusion? 5.13 Have patient diaries been reviewed for reportable adverse events? 5.14 Have any adverse events been discovered through routine monitoring? 6. PROTOCOL DEVIATIONS This section is not to be used in this audit 6.1 Have any patients been entered under a protocol waiver? 6.2 If yes, has this been assessed as being GCP-compliant? 6.3 Have there been any protocol deviations? 6.4 Have any protocol deviations been reported to the sponsor? 6.5 Has the impact of any protocol deviations been assessed? 6.6 Have any serious breaches been identified? SOP10 Routine Audit (v3.0) Page 19 of 34

20 6.7 Have any serious breaches been reported to Sponsor* MHRA* REC* Local site R&D* 6.8 Does the trial have a Data Monitoring Committee? 7. SOURCE DATA VERIFICATION This section is not to be used in this audit 7.1 Is this an audit of All participants Random sample 7.2 Are CRFs present for all consented participants?* 7.3 Has black ink been used on all study documentation? 7.4 Have any corrections, additions, or deletions to the CRFs or other documentation been dated and initialled?* 7.5 Do any CRFs or other study documents contain any of the following entry error omission illegibility 7.6 Have all those that have recorded information been delegated to do so by the investigator and recorded in the delegation log? 7.7 Is there evidence that the delegated duties are periodically reviewed? SOP10 Routine Audit (v3.0) Page 20 of 34

21 7.8 Is there evidence of persistent non-compliance with delegated duties? 7.9 Have all protocol required procedures been carried out by a person with delegated authority according to the delegation log? 7.10 Does the data recorded in the CRF match the source data? 7.11 Do all results recorded match for date and time with the source data? 7.12 Are patient identifiers consistent across all records? 8. DATA PROTECTION This section is not to be used in this audit 8.1 Where is data (paper & electronic) being stored (site/building/office)? 8.2 Where is data being accessed (site/building/office)? 8.3 Are all data protection arrangements being carried out as defined in the REC application? Access to patient records by those outside the healthcare team Electronic transfer of data Sharing personal data with other organisations Export of data outside EEA SOP10 Routine Audit (v3.0) Page 21 of 34

22 8.3.5 Use of personal addresses, postcodes, faxes, s or telephone numbers Use of audiovisual recording devices 8.4 Is data being stored, processed & backed-up using the following Shared network storage Personal network storage inbox/folders External hard drive Local drive USB pen drive Optical media (CD/DVD) Non Trust/University provided equipment (pc/laptop, external drive) Non Trust/University provided storage (personal account) Mobile devices (Blackberry, Phone, PDA) Other (please specify) 8.5 Is data being sent/received to/from Third parties by the following means Trust/University system NHS.net Other system (Googl , Hotmail) Secure File Transfer via internet Postal/Courier service Fax from/to safe haven SOP10 Routine Audit (v3.0) Page 22 of 34

23 8.5.7 Fax from/to non-safe haven Other (please specify) 8.6 Is access to personal data restricted to those approved by the REC, according to the REC application? 8.7 Are electronic data files for analysis anonymised? 8.8 Are any computerised systems being used for the study validated? 8.9 Is antivirus software installed on all computers & laptops? 8.10 Is the computer/laptop configured to receive updates to antivirus software on a regular basis? 8.11 Do you have a firewall installed, active, and properly configured on all computers and laptops? 8.12 Do you have disk/file level encryption tools installed on computers, laptops, external drives, and other removable media? 8.13 Do you use encryption tools at disk/file level? 8.14 Is access to your data protected by strong, secure passwords that are now written down or shared with others? 8.15 Do you have a data backup policy? SOP10 Routine Audit (v3.0) Page 23 of 34

24 8.16 Have you tested that your data backups can be restored? 8.17 Is the emergency recovery procedure for retrieving data available? 8.18 Is your IT equipment located in areas that are not easily accessed by patients, visitors, or unauthorised staff? 8.19 Is your IT equipment in a room with adequate locks? 8.20 Are doors/windows locked at times when staff are absent? 8.21 Are computers and laptops protected by anti-theft devices (e.g. security cables)? 8.22 Are laptops locked away at night/weekends? 8.23 Are desktops/laptops protected by a password-based screensaver? 8.24 Do you have an archiving plan for the long term storage of (and access to) data? 8.25 Does your archiving solution ensure long term access to data stored on 'intermediate storage media' (e.g. tape, floppy disks, CDs/DVDs) 8.26 Does your archiving solution ensure data will be 'locked down' once the trial is closed? 8.27 Will any documentation be archived off-site? SOP10 Routine Audit (v3.0) Page 24 of 34

25 8.28 If yes, are details logged with the R&D department? 9. PATIENT RECORDS This section is not to be used in this audit 9.1 Has a label been attached to the patient health record in an appropriate place, stating that the patient is taking part in a clinical trial, according to local Trust policy? 9.2 Is there a copy of the consent form in the patient health record? 9.3 Is there a copy of the patient information sheet in the patient health record? 9.4 Is there a copy of a GP letter/consultant letter (as per REC approval) in the patient health record? 9.5 Does the patient health record include clear documentation related to the following activities: The approach to the patient Review of the eligibility criteria Patient consent process Follow-up visits 10. INVESTIGATIONAL MEDICINAL PRODUCT MANAGEMENT This section is not to be used in this audit SOP10 Routine Audit (v3.0) Page 25 of 34

26 10.1 Is there a procedure for the retention and maintenance of a separate pharmacy file by the pharmacy department during the study and following closure? 10.2 Is there adequate collection, recording and maintenance of temperature monitoring records for all locations storing IMPs? 10.3 Are all IMPs stored according to the Protocol or Product Characteristics? 10.4 Is there safe segregation? 10.5 Is there a documented procedure for the return and destruction of IMPs? 10.6 Are certificates of analysis present? 10.7 Are medication receipts present? 10.8 Are shipping records present? 10.9 Is there a documented code break procedure? Is it clear where the code breaks are to be stored? Is the dispensing procedure documented? Has IMP been QP released? Are drug accountability forms present and completed corrrectly? Are the following correct: Correct randomisation SOP10 Routine Audit (v3.0) Page 26 of 34

27 Visits timely and in accordance with the protocol Number of packs correct Dispensing signed and dated by the dispenser Any errors signed and dated Returns counted and recorded Are prescriptions Completed correctly Signed by a person with delegated authority according to the study delegation log Correct dose For the right number of packs In line with IMP accountability Do IMP dispensing signatures match the accountability? Do check signatures match accountability? Has unused medication been returned? Has unused medication expired? Are further supplies of IMP required at this site? Where IMP is stored outside of pharmacy, are the storage arrangements compliant with the regulations? SOP10 Routine Audit (v3.0) Page 27 of 34

28 11. HUMAN TISSUE ACT This section is not to be used in this audit 11.1 What types of human tissue or other biological material are included in the study 11.2 Does the study involve taking new samples primarily for research purposes (i.e. not surplus or existing stored samples). If so, Who collects the samples Are the samples being removed from living donors Are the samples being removed from the deceased Has consent been taken to use the tissue for this study Has consent been taken to use the tissue for future research 11.3 Does the study involve the use of surplus tissue or existing stored samples. If so, Has consent been obtained previously to use the samples for research Who is the holder of the samples Are any of the samples imported from outside the UK 11.4 Are the samples be stored: SOP10 Routine Audit (v3.0) Page 28 of 34

29 In fully anonymised form In linked anonymised form In a form in which the donor could be identifiable to researchers 11.5 Are samples stored in suitable, secure environments (precautions taken to minimise risk of damage, theft or contamination) 11.6 Are storage conditions monitored and recorded (e.g. freezer and incubator temperatures, liquid nitrogen levels) 11.7 Are contingency plans in place in case of storage facility failure 11.8 Is the tissue being used in line with the REC approval 11.9 Are any tissues or cells being used for human application Does the study involve the analysis or use of human DNA What will happen to the samples at the end of the study Return to current holder of the samples Transfer to another tissue bank Storage by research team pending ethical approval for use in another project SOP10 Routine Audit (v3.0) Page 29 of 34

30 Storage by research team as part of a new research tissue bank Storage by research team of biological material which is not relevant material for the purposes of the Human Tissue Act Disposal in accordance with the Human Tissue Authority Code of Practice Other Not yet known Have any samples been destroyed. If so, When was it destroyed How it was destroyed Reason for destruction Was consent was given for destruction 12. MEDICAL DEVICES This section is not to be used in this audit 12.1 How many devices are being investigated in this study 12.2 Is the study a clinical investigation undertaken by the manufacturer for CE marking purposes? 12.3 If so, does the study involve: A non-ce marked medical device A CE marked device which has been modified SOP10 Routine Audit (v3.0) Page 30 of 34

31 A CE marked device, which is being used outside its intended purpose Clinical investigation of a non-ce marked medical device, which has been manufactured "in-house" in a healthcare establishment Clinical investigation of "off-label" use of a medical device by a clinician Device class AIMD Device class III Device class b Device class a Device class I Is the investigational device regulated under the Active Implantable Medical Devices Directive 90/385/EEC Is the Chief Investigator a qualified practitioner in accordance with ENISO Is this a performance evaluation of an in vitro diagnostic device (PEIVDD) 12.5 Is this a research study of a CE Marked device 12.6 If so, does the study involve: Investigation of a new medical device Investigation of new implantable material Use of an existing product outside the terms of its CE market intended purpose SOP10 Routine Audit (v3.0) Page 31 of 34

32 Use of a modified product Use of an existing product within its CE market intended purpose 12.7 Are device-related prodedures performed in line with the approved REC form and protocol Is the manufacturer the same organisation named as lead sponsor for this investigation 12.9 If identified a legal representative has been identified, is this organisation acting as the Authorised Representative for the investigational device manufacturer as defined in the Medical Device Directive 93/42/EEC and Active Implantable Medical Devices Directive 90/385/EEC 13. EQUIPMENT This section is not to be used in this audit 13.1 Is there a SOP for the maintenance, servicing and calibration of equipment? 13.2 Has new equipment been purchased for used in this study? If so Will it be regularly calibrated (is there a documented system for this)? Has is been electrically tested? SOP10 Routine Audit (v3.0) Page 32 of 34

33 Is it insured? 13.3 Are records kept and retained for the maintenance/servicing for all equipment used as part of the study, including those for general use? 13.4 Are records kept and retained for the calibration of all equipment used as part of the study, including those for general use? 13.5 Is there a system for periodic calibration of measuring and test equipment? 13.6 Is there documented responsibility for periodic calibration/servicing of measuring and test equipment? 13.7 Are there contingency plans for the failure of a piece of equipment? 13.8 Are staff aware of how to report equipment failure? 13.9 Are defective or out-of-calibration instruments removed from use? Is the equipment registered under the Trust arrangements (i.e. Risk Management, Medical Engineering)? SOP10 Routine Audit (v3.0) Page 33 of 34

34 13.11 Do measuring and test equipment records and labels indicate date of last calibration, person performing calibration, and when next calibration is due? Are gauges and calibration instruments calibrated against certified standards? The copyright of the content of MAHSC MAJIK vests in the Manchester Academic Health Science Centre and permission for copying or distribution of the content is given only with the condition that written reference to the Manchester Academic Health Science Centre is always made as an acknowledgement of MAHSC s copyright, and that this condition is also included within said acknowledgement. SOP10 Routine Audit (v3.0) Page 34 of 34