STANDARD OPERATING PROCEDURE

Transcription

1 STANDARD OPERATING PROCEDURE Title Reference Number Corrective and Preventative Action SOP-QMS-008 Version Number 2 Issue Date 29 th Sep 2016 Effective Date 10 th Nov 2016 Review Date 10 th Nov 2018 Author(s) Reviewer(s) Melanie Boulter, QA Auditor Teresa O Leary, Head of Regulatory Compliance Authorisation (Original signatures are retained by Research & Innovation) Dr Stephen Ryder Director of Research & Innovation Dr Stephen Fowlie Medical Director 01 st Aug nd Sep 2016 USERS OF THIS STANDARD OPERATING PROCEDURE MUST REFER TO TO ENSURE THE MOST CURRENT VERSION IS BEING USED

2 Page 2 of 8 1. Document History Version Number Issue Date Reason for Change 1 30 th May 2014 Original SOP th Sep 2016 Biennial Review and updated based on Audit

3 Page 3 of 8 2. Introduction Sponsors must ensure that there are systems in place to address quality and/or compliance deficiencies or any other issues ( deficiencies ) identified on studies that cannot be resolved by the study team or sponsor within an appropriate timeframe. Deficiencies that require formal monitoring by the sponsor will be added to a corrective and preventative action (CAPA) form. The CAPA form will include details of the deficiency and staff responsible for implementing appropriate corrective and preventative action together with a timeframe and allows the escalation of deficiencies to senior management when necessary. 3. Purpose and Scope This standard operating procedure (SOP) describes the process for the initiation, tracking and recording of CAPAs to resolve deficiencies identified from various sources including, but not limited to, audits conducted by- or on behalf of- Nottingham University Hospitals NHS Trust (NUH). This SOP will apply for studies sponsored by NUH. For studies not sponsored by NUH any deficiencies must be reported to the individual study sponsor in the first instance. Individual sponsors may contact NUH for support on addressing any deficiencies pertaining to their research study being conducted at NUH. 4. Responsibilities All Research Staff Any staff member undertaking research activities for an NUH sponsored study is responsible for the identification and reporting of deficiencies to the sponsor. Research staff will participate in investigations as applicable, and may act as CAPA owner. CAPA Owner Ensure completion of assigned CAPA. Sponsor (fulfilled by the Research and Innovation (R&) department on behalf of NUH as sponsor) The R&I Head of Regulatory Compliance (HRC) will co-ordinate completion of assigned CAPA, and ensure it is appropriately documented and tracked to completion. The HRC or QAA will escalate any critical deficiencies to the Director and/or Deputy Director of R&I. The Director and/or Deputy Director of R&I will support resolution of critical deficiencies, and may escalate these to the Clinical Director and/or Medical Director.

4 Page 4 of 8 5. Definitions CAPA CMD CTIMP Deficiency GCP HRC ICH NUH QA QAA R&I Serious Breach SOP TMF 6. Procedure Corrective and Preventative Action Clinical Investigation of a Medical Device Clinical Trial of an Investigational Medicinal Product Event or circumstance which affects, or has the potential to affect, the overall quality and compliance of the research study or risk to NUH Good Clinical Practice Head of Regulatory Compliance International Conference on Harmonisation Nottingham University Hospitals NHS Trust Quality Assurance Quality Assurance Auditor Research and Innovation A breach of the conditions and principles of GCP in connection with a study, or of the protocol relating to a study, which is likely to effect to a significant degree (a) the safety or physical or mental integrity of the participants; or (b) the scientific value of the study. This also includes serious and/or repeated non-compliance with applicable regulations and/or the protocol Standard Operating Procedures Trial Master File 6.1 Identification of a Quality or Compliance Deficiency Deficiencies may be identified by research teams, study managers, third party providers, monitors, auditors or regulatory inspectors. For a significant deficiency that may potentially be a serious breach, this must be done within 24 hours of becoming aware it. Any staff member may also report deficiencies to R&I by (ResearchSponsor@nuh.nhs.uk), by telephone ( ) or in person by visiting the Nottingham Health Science Partners, C-Floor, South Block, QMC. R&I should also be contacted for queries about research quality or compliance. R&I accepts deficiencies identified from (but not limited to): i. Staff Observations; ii. Audits; iii. Deviations;

5 Page 5 of 8 iv. Regulatory Inspections; v. Urgent Safety Measures; vi. Suspected Fraud or Misconduct; vii. Potential Serious Breaches. 6.2 Implementing Corrective and Preventative Action On receipt of the deficiency notification R&I will determine the classification of the deficiency (see Appendix 2) and assess any CAPA that may have already been implemented and by whom as provided in the initial notification Minor Deficiencies Minor deficiencies do not require CAPA reporting but this may be initiated if further action to resolve the minor deficiency is required. If it is felt a CAPA is required this will be communicated back to the relevant staff/department. All CAPA must be documented (CAPA Form (TAFQ00801)), this form contains guidance on how to complete which can be deleted once a CAPA is drafted. Several recurring minor deficiencies should be re-classed as major and handled as described in section Major or Critical Deficiencies After receiving notification of a major deficiency the HRC, or delegate, must initiate a Corrective and Preventative action plan. The HRC will raise a CAPA Form (TAFQ00801) and record the CAPA by entering all relevant details onto the CAPA log (TAFQ00802) taking the next sequential reference number. The CAPA numbering scheme is: CAYY-XX. A suitable CAPA owner will be identified through discussion and agreement with the responsible individual/department, and the form sent to them to complete. The CAPA owner will complete the CAPA form as far as proposing (as appropriate): i. Corrective actions in order to address the actual deficiency; and ii. Preventive actions in order to address any systematic failures that may allow recurrence of deficiency.

6 Page 6 of 8 When considering preventive actions the CAPA owner should explore and, where reasonable, investigate the root causes of the reasons for the deficiency. The CAPA should: i. Specify exactly what must be accomplished; ii. Give a measure that can be determined to show that the action has been achieved; iii. Only set actions that may reasonably be completed; iv. The action must not lose sight of the original deficiency; v. Define the deadline for completion. The CAPA owner must assess if a route cause analysis is required and provide details of the root cause. The CAPA owner returns the CAPA form to the HRC or delegate. The HRC or delegate then reviews the CAPA form to assess whether the proposed actions adequately address the deficiency and its root cause. If acceptable the HRC or delegate, will approve the CAPA, retain a copy for R&I records and return the original to the CAPA owner to complete the task as stated. After completion of all actions the CAPA owner will update the CAPA form and send the form back to the HRC or delegate. The HRC or delegate will assess whether the CAPA reported is complete and effective in addressing the original deficiency. The HRC or delegate will update the CAPA form to close the actions and file in R&I files and the TMF, if study-related. CAPA owners must notify the HRC, or delegate, of any delays with the completion of assigned actions. The HRC, or delegate, will escalate all critical deficiencies related to CTIMPs & CMDs to the Director and/or Deputy Director of R&I. Dependent on the deficiency the Director and/or Deputy Director of R&I may deem it appropriate to escalate further to the Clinical Director and/or Medical Director (i.e. in cases of fraud and misconduct). R&I may decide to withdraw or suspend sponsorship for the study in some cases of major or critical deficiencies. This will be communicated to the Chief Investigator and the appropriate processes followed (SOP-RES-001 Sponsorship and SOP-RES-025 End of Study Notification and Premature Discontinuation of a Study). 6.3 Corrective and Preventative Action Review Periodically (usually monthly) the HRC or delegate, will review the status of outstanding CAPAs and escalate any significant delays to CTIMP & CMD related CAPAs the Director and/or Deputy Director of R&I.

7 Page 7 of 8 The HRC or delegate will chase the CAPA owner of any actions that are not closed within the agreed timelines. Failure to implement the CAPA within an appropriate timeline may affect the continuation of NUH sponsorship for a study. The HRC or delegate will communicate CAPA progress as part of quarterly QA metrics to senior management and R&I team. 7. References and Associated Documents International Conference on Harmonisation Guidelines on Good Clinical Practice E6 (R1) TAFQ00801 TAFQ00802 TAFR01701 SOP-RES-001 SOP-RES-025 CAPA Form CAPA Log Deviation Report Sponsorship End of Study Notification and Premature Discontinuation of a Study

8 Page 8 of 8 8. Appendices Appendix 1. Classification of Deficiencies Classification Definition A single event whereby compliance with procedures, instructions, regulations or sponsor requirements has lapsed. Immediate corrective action may be implemented so there is no overall impact on participant safety or the outcome of the study. The Minor* isolated event does not suggest failure of the quality management system. N.B. Several isolated events of a similar nature may be reclassified as Major. A single event or several isolated events, whereby procedures, instructions, regulations or sponsor requirements have not been followed. Corrective action may be implemented but the event(s) Major* has the potential to impact participant safety or the overall outcome of the study. The event(s) indicate a flaw or gap in the quality management system which may be rectified following implementation of appropriate preventive action. A single event, or series of events, whereby procedures, instructions, regulations or sponsor requirements have not been followed. Corrective action may be implemented, or may not be possible. The event(s) are deemed to be a high risk to Critical* participant safety or to the outcome and/or the integrity of the study. The event(s) indicate the total breakdown or inadequacy of the quality management system. Preventive action and quality improvements must be implemented with immediate effect. *Quality issues may be re-classified following an investigation.