5Pre-Inspection Dossier Complete list of Clinical Trials (from May 2005)Organisational chartsOverview of all facilitiesDescription of archiving arrangementsSOP indexDetailed procedures in relation to:Trial managementQuality control and assuranceComputerised systemsEquipment maintenanceSupply of Investigation Medicinal ProductLaboratory proceduresActivities carried out by CU or contracted out by CU
6Clinical Trial Activities Any activity involved in the running of Clinical trials at our institutionArchivingSOPsStatisticsAdverse Event reportingContractsData ManagementDrug ManagementTrial reportingProject ManagementTrainingLaboratoryRandomisationComputer SystemsRegulatory approvalsStudy MonitoringTrial Files
7What happens during the visit? 1 week inspection by at least 2 GCP InspectorsDocumentation reviewUniversity/School/Unit SOPsFacility VisitsInspection of several clinical trials to test systemsInterviews with key personnel, e.g.Chief / Principal InvestigatorResearch teams e.g. Research Fellow, Research NurseRACDLaboratoriesITArchiving facilitiesInspection plan can changeSo what is likely to happen during the visit?We would expect at least 2 GCP inspectors to be on site.They may wish to see a tour of some of the facilities e.g. the CRF, pharmacy, laboratories etc.They may ask to see additional documentation not submitted as part of the Pre-Inspection Dossier – for example other policies or SOPs . As you can imagine, we had to be selective as to what we included in one lever arch file.They will want to inspect several clinical trials to test systems. These could be studies which are ongoing or studies that have closed since May If they decide they are particularly interested in close down or archiving systems they may well choose a study that has closed.Who will they wish to interview? Well of course we can’t be certain but from past experience, for the chosen trials they will usually interview the Chief/Principal Investigator and other key members of the same research team. They usually interview these individuals separately.We expect they will interview key individuals in the R&D Office and probably key individuals in Pharmacy, the laboratories, medical records, IT, radiology.As this is a statutory inspection, individuals are expected to make themselves available. As there is usually 4-6 weeks notice, clinicians would be expected to make alternative arrangements for clinics, ward rounds etc. The R&D office will of course do everything it can to try and schedule the timetable of interviews to suit both the MHRA AND staff here at the Trust. Once we know which studies are to be inspected in detail, we will ask for a named contact in the trial team to liaise with the R&D office over the logistics of the Inspection as we will be expected to provide suitable rooms for interview, access to office space and access to photocopiers etc.A member of the R&D Office will attend each interview as notes must be taken.
8Inspection outcomes 3 categories of findings: Critical: evidence that i) the safety, well-being or confidentiality of trial subjects have been or have potential to be jeopardised,ii) the clinical trial data are unreliableiii) there are a number of Major non-compliances, indicating a systematic quality assurance failure.insufficient or untimely corrective action regarding previously reported Major non-compliancesMajor:significant and unjustified departure from legislative requirements that may develop into a critical issue unless addressed,a number of departures from legislative requirements and/or established GCP guidelines, indicating a systematic quality assurance failure.Other:departure from legislative requirements and/or established GCP guidelines, but it is neither Critical nor Major.
9Response to Findings Organisation must respond within 30 days Critical Findings or a number of Major Findings may lead to suspension of one or all CTIMPs in the organisationOrganisation responseAnalysis of findingsCorrective ActionPreventative ActionPlans of assessing effectiveness of preventative actionTimelinesDisputed findings
10Common Findings Contract & Agreement Preparation Lack of written agreements with collaboratorsInconsistencies between protocol and contractDelegation of duties without agreements/systems in placeLack of identification of CI and all trial team at outsetQuality SystemLack of SOPsInsufficient time between issuing and implementing SOPs, leading to training issuesTeam meetings not documentedTrainingInadequate knowledge of Clinical Trial RegulationsLack of GCP training amongst trial teamInformed ConsentNo record of consentIncorrect version
11Common Findings Investigational Medicinal Product (IMP) management Inadequate provisions for storage of IMPsInsufficient records for the chain of custodyInadequate procedures for QP releaseLack of documentation confirming role of Pharmacy/CIPharmacovigilanceInadequate Pharmacovigilance systems and/or inadequate use of systems in placeLack of awareness of legislative requirementsStandardisation or arrangements for un-blinding SAEs arising from blinded trialsAnnual safety report to MHRA not madeData managementSecurity of trial documents/dataInadequate retention periodLack of clarity of data entry and data query processes (Source Data Verification)
12Common Findings Information Management Lack of assurance that systems are fit for purposeLack of evidence of system securityNo clarity on arrangements for backing up dataRegulatory Affairs (e. g. Clinical Trial Authorisations)Remarks on MHRA approval letters not followed upUnclear indemnity arrangementsUnclear sponsorship arrangements for DDX studiesAnnual and end of study reports not sentFiling of essential documentsPoorly maintained site filesPoor document control and managementForms not signed or not completed correctlyLaboratoryNo evidence of how equipment is maintained, calibrated and serviced
13University (RACD) Preparations Pre-Inspection DossierAwareness RaisingDelegation of dutiesReview of Clinical Trial listClinical Trial Monitoring Visits - essential documentationMHRA Inspection working groupRisk Assessment/GAP analysis – based on common findings from previous MHRA inspectionsIndividualised preparation plans
14How can Research Groups/Units prepare? Awareness raisingFamiliarity with legislation, internal and external guidanceICH GCP (Topic E6)University Research Governance web pageGAP analysisEssential documentation / Unit SOPsAction plan
15How can Researchers prepare? Familiarity with legislation, internal and external guidanceICH GCP (Topic E6)University Research Governance web pageEssential Documentation - Self-assessment of the trial using Trial Master File checklistApprovalsDocument ControlIMP managementDelegation LogsSOPsPharmacovigilanceEquipment
16Summary Anyone involved in Clinical Trials Co-operation and engagement Early PreparationAction plan to remedy issues
17Contacts Research Governance Team firstname.lastname@example.org X79277 ( from Heath)Chris ShawMatthew HarrisKathy Pittard Davies
18Medicines and Healthcare products Regulatory Agency (MHRA) Statutory Good Clinical Practice (GCP) Inspection of Cardiff University