Title: Effective Date: 1-4-17 Review Date: 1-4-20 Author: Joanne Rodger, Senior R&D Manager QA Approval: Richard Cowie, QA Manager Approver: Prof Maggie Cruickshank, R&D Director Approver: Prof Steve Heys, Head of School Document History Version Description of update Date Effective 1 Change of number for Q-Pulse 2-10-15 2 Reformatted Reference to Device Trials at 1.1 and 3.1 Removal of reference to Compliance report at 3.2 Definition of MHRA findings at 3.20 1-4-17 1. Scope 1.1 This SOP applies to Clinical Trials of Investigational Medicinal Products (CTIMPs) that are within the scope of the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended and medical device trials sponsored, co-sponsored or hosted by the University of Aberdeen (UoA) and/or NHS Grampian (NHSG), which are subject to inspection by the MHRA. 1.2 This SOP applies to all research team members and staff and departments supporting, coordinating or participating in CTIMPs or Medical device Trials sponsored, co-sponsored or hosted by UoA and/or NHSG. 2. Responsibilities Sponsor Research Governance Chief Investigator Support researchers in preparation and participation in. Inform relevant researchers and UoA/NHSG staff of impending inspections. Ensure documentation is accurate, up to date and inspection ready at all times. Provide necessary documentation to the Sponsor for preparation of an inspection dossier or to MHRA inspectors upon request. 3. Procedure Medicines and Healthcare products Regulatory Agency (MHRA) 3.1 The MHRA conduct three types of Good Clinical Practice (GCP) inspection. Only two of these types are applicable to non-commercial research; 3.1.1 Risk based inspection uses previous inspection history information, organisational changes and any intelligence gathered, to determine an organisation s control of their risk. The resulting risk assessments will be categorised into high, medium and low risk. Inspections are prioritised for organisations with the highest risk category. However, for MHRA internal control purposes, a small proportion of organisations from the medium and low risk categories shall be randomly selected for Page 1 of 5
inspection. The majority of GCP inspections conducted by the MHRA are conducted under the Statutory GCP-risk-based inspection programme and are either: Systems Inspections the site(s) or Sponsor is selected for inspection as part of a routine inspection programme of systems employed in the conduct of the trial. Study Specific Inspections - the site(s) or Sponsor is selected for inspection as part of a routine inspection programme relating to a specific trial. 3.1.2 Triggered inspections (for cause) the site is selected for inspection due to suspicion of significant contractual or regulatory non-compliance, scientific misconduct or fraud. In rare circumstances, notification of triggered inspections may not be given in advance, nor the inspection plan shared with the organisation. Notification of inspection by the MHRA Study specific or triggered inspections 3.2 The CI/PI may be formally notified by the MHRA that a particular clinical trial shall be subject to either a routine study specific GCP inspection or a triggered inspection. In such circumstances the Sponsor/R&D should be notified immediately on 01224 551121. The sponsor/r&d shall advise on the action to be followed. 3.3 In rare circumstances the MHRA may arrive to undertake a triggered inspection. In such circumstances the Sponsor/R&D should be notified immediately on 01224 551121. The sponsor/r&d shall advise on the action to be followed. Systems inspections 3.4 The Sponsor is formally notified by the MHRA that the organisation or site has been selected for an inspection. 3.5 The formal notice of inspection will request a dossier detailing activities performed by the organisation, or site, to be submitted by a date specified by the MHRA. This dossier shall list the documents that are required by the MHRA prior to the inspection. 3.6 An individual from the organisation or site must be nominated to be Inspection Coordinator and shall be responsible for liaising with the MHRA to ensure coherent communication on matters relating to the inspection. 3.7 On submission of the dossier the MHRA shall acknowledge receipt of the complete dossier. They shall advise of the potential inspection date and may request further information. Preparation for an MHRA inspection 3.8 The MHRA shall provide a proposed timetable for the inspection detailing the departments which may be inspected and staff who shall be interviewed. The inspection coordinator shall inform departments/individuals as soon as possible and ensure that staff shall be available for interview. If the proposed timetable is not suitable, the inspection coordinator shall advise the MHRA. 3.9 For sponsor wide system inspections, the Sponsor must ensure all relevant staff are appropriately prepared for the MHRA inspection. Page 2 of 5
Documentation required for an MHRA inspection 3.10 The Sponsor, CI and relevant staff collectively must ensure that all appropriate documentation requested by the MHRA is available. 3.11 The documentation that may be reviewed includes, but is not limited to: Closed minutes from Data Monitoring Committee (DMC) available on request to authorised personnel as appropriate. Completed Case Report Form (CRF) Completed consent forms along with relevant Participant Information Sheet Insurance Investigator Site File (ISF) Laboratory records Patient hospital records/source documentation (If there are legitimate reasons why a patient s hospital notes cannot be available, this must be explained, if possible in advance of the inspection) Pharmacy drug accountability records Publications arisen from the trials Sponsor committee minutes Sponsor risk assessment Sponsor SOPs Training Records Trial Contracts Trial Databases Trial Master File (TMF) Study specific SOPs. (The above list includes any documents that may have been archived). During an MHRA inspection 3.12 The CI and staff from relevant departments must make themselves available during inspection, should they be required by the inspector(s) to provide information or documentation. 3.13 The MHRA Inspector(s) must be accompanied at all times during their visits to the relevant departments. The Inspector(s) shall adhere to guidelines for preparation of entry into restricted or high risk areas ie they shall follow any hand washing and dress code guidelines. 3.14 Interviewees shall answer MHRA Inspector(s) questions honestly and succinctly to the best of their knowledge. 3.15 Interviewees may update or clarify information given during an interview at any time throughout the inspection via the Inspection Coordinator. 3.16 All interviews shall be attended by a scribe to record the discussions. 3.17 During an interview the MHRA inspector(s) may request a specific document or piece of information. Any such request shall be conveyed to the appropriate personnel and the document delivered to the inspector(s). Page 3 of 5
3.18 A record shall be kept of any documentation given to the inspector(s). Close-out of an MHRA inspection 3.19 At the end of the inspection, a closeout meeting shall take place and the inspector(s) shall provide verbal feedback on the findings. 3.20 A detailed written report shall be provided by the MHRA within 30 working days of the inspection. The written report shall document all findings from the inspection as: Critical: a deficiency that adversely affects the rights, safety or well-being of patients, or that poses a potential risk to public health, or that represents a serious violation of applicable legislation and guidelines. All such findings are reviewed by the MHRA and may be recommended for prosecution by the Crown Office and Procurator Fiscal Service (COPFS). Major: a deficiency that could potentially affects the rights, safety or well-being of patients, or that could potentially pose a risk to public health, or that represents a violation of applicable legislation and guidelines. Minor: a deficiency that would not be expected to adversely affect the rights, safety or well being of patients. 3.21 A response to the written report is expected within the timeline specified by the inspector(s); usually 30 calendar days. This response should be coordinated by the Inspection Coordinator as appropriate. 3.22 A dialogue may be held with the MHRA to clarify findings and proposed Corrections and Corrective and Preventative Actions (CAPAs). The final written response to the MHRA shall document Corrections and CAPAs and any response timeline. 3.23 When the MHRA are satisfied with the response they will formally accept the CAPA plan, close out the Inspection and issue a GCP inspection statement. Post MHRA inspection follow-up 3.24 An overview of the MHRA Inspection shall be disseminated to researchers by the Research Governance Manager and/or Quality Assurance Manager. 3.25 Any Corrections and CAPAs in relation to inspected projects shall be discussed with the CI and the researcher team as appropriate. 3.26 Any Corrections and CAPAs in relation to Sponsor systems, procedures, SOPs or other Sponsor matters shall be addressed by the relevant governance committee(s). 3.27 Appropriate close out of all CAPAs shall be overseen by Sponsor through the Clinical Research Oversight Group (CROG). 4. Abbreviations and definitions CAPA/CCAPA CI (Correction and) Corrective And Preventive Action Chief Investigator Page 4 of 5
CTIMP MHRA PI TMF Clinical Trial of Investigational Medicinal Product Medicines and Healthcare products Regulatory Agency* Principal Investigator Trial Master File 5. Related documentation and references SOP-QA-2 SOP-QA-7 SOP-QA-15 SOP-QA-32 Training record Trial Master File Management of Medicinal Products used in research Archiving *An executive agency of the Department of Health in the United Kingdom which is responsible for regulating medicines, medical devices and blood components for transfusion in the UK. The MHRA is the competent authority in the UK responsible for human medicines and is responsible for ensuring organisations comply with good clinical practice (GCP) standards. The majority of MHRA GCP inspections are carried out under the risk-based compliance programme. This uses information available to the MHRA to determine an organisation s risk and select the highest risk organisations for inspection. In addition a small number of low risk organisations are also selected for routine inspection. Page 5 of 5