Medicines and Healthcare Products Regulatory Agency (MHRA) Inspection

Transcription

1 Standard Operating Procedure: Preparation and Participation in a Medicines and Healthcare Products Regulatory Agency (MHRA) Inspection SOP Number: SOP-QA-30 Version No: 1 Author: Date: (Joanne Rodger, Senior R&D Manager, NHS Grampian) Approved by: Date: (Professor Julie Brittenden, R&D Director, NHS Grampian) Approved by: Date: (Professor Steve Heys, Head of School, University of Aberdeen) Issue Date: Effective Date: Review Due Date: Document History: Version Description of Changes Date Effective 1 Change of number for Q-Pulse (Replaces UoA-NHSG-SOP-018 V2) This SOP will be reviewed at least every 3 years from initial and subsequent issue dates. Page 1 of 7

2 1. PURPOSE/INTRODUCTION 1.1 To describe the process for preparing and participating in an inspection by the Medicines and Healthcare products Regulatory Agency (MHRA). 1.2 Clinical Trials of Investigational Medicinal Products (CTIMPs) that are within the scope of the Medicines for Human Use (Clinical Trials) Regulations 2004 are subject to inspection by the MHRA. 1.3 The MHRA conduct three types of Good Clinical Practice (GCP) inspection. Only two of these types are applicable to non-commercial research Risk based inspection uses information from the Compliance Report, internal information about previous inspection history, organisational changes and other compliance reports, with the results of intelligence gathering, 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 inspection. The majority of GCP inspections conducted by the MHRA are conducted under the Statutory GCP-riskbased inspection programme and are either systems based or study specific: o o Systems Inspections the site(s) or Sponsor is selected for inspection as part of a routine inspection programme of any or all systems employed in the conduct of the CTIMPs. Study Specific Inspections - the site(s) or Sponsor is selected for inspection as part of a routine inspection programme relating to a specific trial. 2. SCOPE 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. 2.1 This SOP applies to CTIMPs that are within the scope of the MHRA, sponsored/cosponsored or hosted by the University of Aberdeen (UoA) and/or NHS Grampian (NHSG). 2.2 Applies to all research team members and members of UoA Research and Innovation (R&I); NHSG Research and Development (R&D) and other departments supporting, coordinating or participating in CTIMPs sponsored/co-sponsored or hosted by UoA and/or NHSG. Page 2 of 7

3 2.3 This SOP may also be used by staff from other NHS areas, or organisations, with prior agreement. 3. RELATED DOCUMENTATION SOP-QA-2 SOP-QA-7 SOP-QA-15 SOPQA-32 Establishing and Maintaining a Training Record Establishing and Maintaining a Trial Master File Management of Medicinal Products used in Research Projects Archiving Data from Interventional Research Projects Involving Human Participants 4. REFERENCES Scottish Executive Health Department Research Governance Framework for Health and Community Care. UK Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004 No. 1031) as amended. National Research Ethics Service/Health Research Authority website Medicine and Healthcare Products Regulatory Agency website (MHRA) Current versions of these documents can be accessed via the Clinical Research Governance and Quality Assurance Website: ICH E9 Guideline Statistical Principles For Clinical Trials Website: ep4/e9_guideline.pdf It is assumed that by referencing the principle regulations, all subsequent amendments made to the principle regulations are included in this citation 4.1 ABBREVIATIONS AND DEFINITIONS CAPA CI CRF CTIMP DMC GCP ISF MHRA NHSG PI R&D Corrective and Preventative Actions Chief Investigator Case Report Form Clinical Trials of Investigational Medicinal Products Data Monitoring Committee Good Clinical Practice Investigator Site File Medicines and Healthcare Products Regulatory Agency NHS Grampian Principal Investigator Research and Development Page 3 of 7

4 R&I RGT TMF UoA Research and Innovation Research Governance Team Trial Master File University of Aberdeen 5. RESPONSIBILITIES 5.1 It is the responsibility of the Sponsor and delegated members of UoA R&I and NHSG R&D to support research staff and departments during preparation and participation in MHRA inspections. 5.2 It is the responsibility of the Chief Investigator (CI) to ensure that documentation is accurate, up to date and inspection ready at all times. 5.3 It is the responsibility of the Research Governance Team (RGT) to inform relevant researchers UoA and NHSG staff involved in CTIMPs of any impending MHRA inspection. 5.4 It is the responsibility of the CI, delegated research staff and Sponsor staff to provide all necessary information and documentation to allow the completion in a timely manner of the MHRA dossier. 5.5 It is the responsibility of the CI, delegated research staff and Sponsor staff to ensure that documentation is made available to MHRA inspectors on request. 5.6 It is the responsibility of the CI and individual research team members, Sponsor staff or support team departments to make themselves available for interview by the MHRA at their request. 6. PROCEDURE 6.1 NOTIFICATION OF INSPECTION BY THE MHRA Study Specific or Triggered Inspections The CI/PI may be formally notified by the MHRA that a particular clinical trial will 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 via R&D on The sponsor/r&d shall advise on the action to be followed. In rare circumstances the MHRA may arrive to undertake a triggered inspection. In such circumstances the Sponsor/R&D should be notified immediately via R&D on The sponsor/r&d shall advise on the action to be followed. Page 4 of 7

5 6.1.2 Systems Inspections The Sponsor is formally notified by the MHRA that the organisation or site has been selected for an inspection. The formal notice of inspection will ask for a dossier detailing activities performed by the organisation, or site, to be submitted by a date specified by the MHRA. This dossier will list the documents that are required by the MHRA prior to the inspection. 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. On submission of the dossier the MHRA will acknowledge receipt of the complete dossier, and may request further information. They will also advise of the potential inspection date. 6.2 PREPARATION FOR THE INSPECTION The MHRA shall provide a proposed timetable for the inspection detailing the departments that may be inspected and staff who will be interviewed. The inspection coordinator should inform these departments/individuals as soon as possible and ensure that staff will be available for interview. If the proposed timetable is not suitable, the inspection coordinator should advise the MHRA of this For sponsor wide system inspections, the Sponsor must ensure all relevant staff are appropriately prepared for inspection. 6.3 DOCUMENTATION REQUIRED FOR AN INSPECTION Sponsor, CI and relevant staff collectively must ensure that all appropriate documentation requested by the MHRA is available 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 Page 5 of 7

6 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). 6.4 DURING THE MHRA INSPECTION 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 The MHRA Inspector(s) must be accompanied at all times during their visits to the relevant departments. The Inspector(s) will be expected to adhere to guidelines for preparation of entry into restricted or high risk areas i.e. they should follow hand washing and dress code guidelines set within the areas being inspected Interviewees should answer MHRA Inspector(s) questions honestly and succinctly to the best of their knowledge Interviewees can update or clarify information given during an interview at any time throughout the inspection via the Inspection Coordinator All interviews will be attended by a scribe to record the discussions During an interview the MHRA inspector(s) may request a specific document or piece of information. Any such request must be conveyed to the appropriate personnel and the document delivered to the inspector(s) A record must be kept of any documentation given to the inspector(s). 6.5 CLOSEOUT OF THE INSPECTION At the end of the inspection, a closeout meeting shall take place and the inspector(s) will provide verbal feedback on the findings 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 and shall Page 6 of 7

7 typically list findings as critical, major or other 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 A dialogue may be held with the MHRA to clarify findings and proposed Corrective and Preventative Actions (CAPAs). The final written response to the MHRA shall document CAPAs and the response timeline 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 All documentation and record of outcomes of the inspection shall be kept by the Sponsor. Copies of documents from study specific inspections may also be kept by the Investigator. 6.6 POST INSPECTION FOLLOW UP An overview of the MHRA Inspection shall be disseminated to researchers Any CAPAs in relation to inspected projects shall be discussed with the CI and the researcher team as appropriate Any CAPAs in relation to Sponsor systems, procedures, SOPs or other Sponsor matters shall be addressed by the relevant governance committee(s) Appropriate close out of all CAPAs shall be overseen by Sponsor through the Clinical Research Oversight Group (CROG). Page 7 of 7