GCP INSPECTION FINDINGS Singapore Research Ethics Conference 2018

Transcription

1 1 GCP INSPECTION FINDINGS Singapore Research Ethics Conference 2018 Sumitra Sachidanandan GCP Inspection Consultant Clinical Trials Branch Health Products Regulation Group Health Sciences Authority Singapore

2 2 OUTLINE GCP Inspection Framework Strategy for conducting GCP Inspections ( ) GCP Inspection Findings ( ) Common Major GCP Inspection Findings ( ) Quality Improvement Initiatives by HSA ( )

3 3 GCP Inspection Framework Sep 2009 Launched GCP Inspection Framework Nov 2009 Conducted first GCP Site Inspection. Nov 2011 Conducted first GCP Systems Inspection. May 2017 Conducted first CRM Systems Inspection. Conducted 100 th inspection. Jul 2017 Conducted first MS IIT Systems Inspection. Dec 2017 Conducted 107 GCP inspections to date.

4 4 Objectives of GCP Inspections To safeguard the Rights, Safety and Well-Being of trial subjects. To verify the Quality and Integrity of the clinical trial data submitted to the Regulatory Authority. To assess Compliance to protocol and applicable regulations, guidelines and standard operating procedures for clinical trials.

5 5 Strategy for Conducting GCP Inspections Considerations for routine GCP Inspections have evolved over the years: Baseline assessment of how clinical trials are conducted in Singapore: Therapeutic Area (based on volume of CTC submissions) Recruitment status Clinical trial experience of Sponsors, Contract Research Organisation (CROs) and Principal Investigators Risk-based approach Common GCP Inspection Findings Investigator-initiated clinical trials (IITs) Systems GCP Inspections on ICF and IP Port-over of clinical trials regulations Substituted informed consent in vulnerable populations Clinical Research Material (CRM) Inspections Multi-sponsor IIT Inspections

6 6 Classification of GCP Inspection Findings Critical: Conditions, practices or processes that adversely affect the rights, safety or well being of the subjects and/or the quality and integrity of data. Major: Conditions, practices or processes that might adversely affect the rights, safety or well-being of the subjects and/or the quality and integrity of data. Other: Conditions, practices or processes that would not be expected to adversely affect the rights, safety or well being of the subjects and/or the quality and integrity of data. Comments: The observations might lead to suggestions on how to improve quality or reduce the potential for a deviation to occur in the future.

7 Classification of GCP Inspection Findings (N=95) (N=62) 2012 (N=26) 2013 (N=24) 2014 (N=22) 2015 (N=29) 2016 (N=27) 2017 (N=27) OTHER MAJOR CRITICAL

8 Critical GCP Inspection Findings Case Review Record Keeping SD & CRF Monitoring and Auditing Biological Samples Safety IP Informed Consent Subject Recruitment

9 Major GCP Inspection Findings Case Review Record Keeping SD & CRF Monitoring and Auditing Biological Samples Safety IP Informed Consent Subject Recruitment ISF RA IRB Study Staff (%)

10 Common Major GCP Inspection Findings Informed consent Investigational Product (IP) Case Review

11 Common Major GCP Inspection Findings Informed Consent ( ) Who Study staff was not appropriately qualified to obtain informed consent. Substituted informed consent by legal representative was invalid. 11 What Unapproved informed consent form had been used to obtain informed consent. Subject did not sign the full informed consent form. When How Informed consent not was obtained prior to study procedures. Witness for informed consent process was not impartial. Inappropriate use of impartial witness for informed consent process.

12 Common Major GCP Inspection Findings Investigational Product (IP) ( ) SOPs Lack of written procedures for handling and storage of IP. Lack of quality systems in IP Management. 12 Receipt & Storage Repackaging, Dispensing & Accountability Return / Destruction Labelling IP storage temperature records were not completed in an accurate and contemporaneous manner. For blinded trials, lack of delineation of roles and responsibilities and lack of traceability in IP repackaging. Lack of traceability in IP return / destruction records. IP label was not compliant with regulatory requirements.

13 Common Major GCP Inspection Findings Case Review ( ) 13 Source Documents Source documents did not fulfil the ALCOA principles. Eligibility checklists did not co-relate with protocol. Case Report Forms Discrepancies in source document verification. Protocol compliance Subjects were ineligible for enrollment. Protocol non-compliances had not been reported.

14 Root Cause Analysis of GCP Inspection Findings ( ) Top 3 categories for GCP Inspection Findings have been similar. Informed consent, IP, Case Review Possible reasons for recurrence: New study staff Lack of training Lack of supervision Lack of adequate monitoring Incidence of some common GCP Inspection Findings have reduced Quality Improvement initiatives implemented by HSA. 14

15 Quality Improvement Initiatives by HSA CTB FAQs on HSA Website From the GCP Inspector s Desk Newsletter Upstream consultation on IP Management Template Forms Repository Regulatory Guidance Stakeholder Engagement Training

16 16 Be familiar with regulatory requirements for: Translator Impartial witness ICF should be personally signed and dated. Checkboxes should be personally completed. Subject should receive a signed copy. INFORMED CONSENT PROCESS HOW WHO INFORMATION COMPREHENSION VOLUNTARINESS Obtained by qualified physicians / dentists, authorised by PI to obtain consent. Given by subject or subject s legal representative (if applicable). WHAT ICF should be approved by IRB and HSA prior to use. All ICF amendments should be approved by the IRB. Substantial amendments to ICF should be approved by HSA. Consent should be obtained before any study procedures. WHEN WHERE Consent should be obtained in a conducive environment.

17 17 INVESTIGATIONAL PRODUCT Labelling Compliant with regulatory requirements for IP labelling. Refer to Guidance on Labelling of TP and MP used in CT IP Return / Destruction Logs Return / Destruction Receipt IP shipment receipts IP inventory logs SOP Authorised staff IP dispensing and Accountability Logs IP should be used in accordance with the protocol. Dispensing and Accountability Repackaging / Relabelling Storage Access should be secure and limited IP storage temperature logs Adhere to GMP requirements. ATTRIBUTABLE, LEGIBLE, CONTEMPORANEOUS, ORIGINAL, ACCURATE

18 CASE REVIEW 18 Traceabili ty Subject Identifiers required if DCF is used as SD. Data should be captured in accordance with study protocol. Document and report noncompliances. CRF data should be consistent with SD. Protocol ABC Subject ID: Visit No.: 1 Study Procedures DATA COLLECTION FORM Subject Initials: ABC Visit Date.: 1 Dec 2016 A Attributable L - Legible C -Contemporaneous O - Original A Accurate Amendments should be initialled and dated Purpose: SD / CRF? Requires IRB approval Should be compliant with protocol May be required to be updated for protocol amendments. Completed by: Version Control Version Dated: 1 Nov 2016 Page 1 NB: SD = Source Documents; CRF = Case Report Form

19 19 REFERENCES Health Products (Clinical Trials) Regulations Health Products (Therapeutic Products as Clinical Research Materials) Regulations ICH E6 (R2) GCP Guidelines HSA Guidelines CTB FAQs

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