Introduction
Clinical trials on medicinal products currently must comply with the Medicines Act (Chapter 176, Sections 18 and 74), the Medicines (Clinical Trials) Regulations and the Singapore Guideline for Good Clinical Practice (SGGCP).
The GCP Inspection Framework was implemented in September 2009.
Definitions
Inspections are defined by the SGGCP as the act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and / or contract research organisation's (CRO's) facilities, or at other establishments deemed appropriate by the regulatory authority(ies).
Scope
The GCP Compliance Inspection Framework applies to clinical trials on medicinal products, where a Clinical Trial Certificate (CTC) has been issued by the Health Sciences Authority. GCP Site Inspections may either be protocol-specific or systems. Systems that may be inspected include Investigator Site Files, Informed Consent, Investigational Products, Pharmacovigilance, Biological Samples, Monitoring, Data Management, Biostatistics, Final Reports etc.
Objectives
4.1 Objectives of GCP Site Inspection (Protocol-specific)
| (i) | To safeguard the rights, safety and well-being of trial subjects. |
| (ii) | To verify the quality and integrity of the clinical trial data submitted to the Regulatory Authorities. |
| (iii) | To assess compliance to the protocol, applicable regulations, guidelines and standard operating procedures for clinical trials. |
4.2 Objectives of GCP Site Inspection (Systems)
(i) To safeguard the rights, safety and well-being of trial subjects. (ii) To verify the quality and integrity of the clinical trial data submitted to the Regulatory Authorities. (iii) To assess compliance to the protocol, applicable regulations, guidelines and standard operating procedures for clinical trials. (iv) To assess whether a system is suitably designed, controlled, maintained and documented to fulfill the objectives for which it has been set up. (v) To identify areas for quality improvement.
Criteria
Compliance to the following standards will be determined during the GCP Inspections:
| (i) | Protocol |
| (ii) | Medicines (Clinical Trials) Regulations |
| (iii) | Singapore Guideline for Good Clinical Practice (SGGCP) |
| (iv) | Standard Operating Procedures (SOPs) for conducting clinical trials |
Types of GCP Inspections
GCP Inspections can either be routine, triggered or conducted in response to a pre-marketing approval application.
| (a) | Routine GCP inspections are done announced and apply to ongoing clinical trials. |
| (b) | Triggered GCP inspections are ad-hoc inspections that may be triggered as a result of requests or complaints or reports to HSA on suspected violations of the regulations. Such types of inspections may be done announced and apply to ongoing or completed clinical trials. |
| (c) | Pre-marketing approval application inspections are usually done announced and apply to completed clinical trials. |
GCP Site Inspection Process
The GCP Site Inspection Process is summarized in the flowchart below:
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Preparation for GCP Site Inspection
A Notice of GCP Site Inspection will be sent to the Principal Investigator (inspectee) within 30 working days prior to the proposed date(s) of the GCP Site Inspection.
The inspectee will be required to submit a GCP Site Inspection Dossier to HSA within 15 working days of receipt of the Notice of GCP Site Inspection, along with some documents.
The inspectee will be provided with a GCP Site Inspection Preparation Checklist for Site to help the site prepare for the upcoming inspection.
Conduct of GCP Site Inspection
The GCP Site Inspection will start with an Opening Meeting where the Compliance Inspectors will explain the regulatory framework for the conduct of GCP Inspections; outline the objectives, scope and criteria of the GCP Site Inspection; confirm the agenda; and also confirm that the resources, essential documents and facilities required for the GCP Site Inspection are available. The Principal Investigator or designate would be required to present a general overview of the clinical trial at this meeting. Information pertaining to subject recruitment, informed consent process, investigational product management, safety reporting and biological sample handling may be included.
During the GCP Site Inspection, the Compliance Inspectors will interview study staff to determine how the clinical trial is conducted at the site, and review essential documents pertaining to the clinical trial being inspected. The Compliance Inspectors may also visit site facilities used to conduct the clinical trial being inspected.
At the end of the GCP Site Inspection, there will be a Closing Meeting where the Compliance Inspectors will present the GCP Inspection Findings and gradings to the inspectee; ensure that results of the inspection are clearly understood and acknowledged by the inspectee; and provide an appropriate time frame for the inspectee to present the Corrective Action and Preventive Action Plan.
During the GCP Site Inspection, the Compliance Inspectors will interview study staff to determine how the clinical trial is conducted at the site, and review essential documents pertaining to the clinical trial being inspected. The Compliance Inspectors may also visit site facilities used to conduct the clinical trial being inspected.
At the end of the GCP Site Inspection, there will be a Closing Meeting where the Compliance Inspectors will present the GCP Inspection Findings and gradings to the inspectee; ensure that results of the inspection are clearly understood and acknowledged by the inspectee; and provide an appropriate time frame for the inspectee to present the Corrective Action and Preventive Action Plan.
Follow-up from GCP Site Inspection
The GCP Inspection Findings will be graded as critical, major or other. In addition, the Compliance Inspectors may make some observations and recommendations (known as “comments”) in the report.
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Once the GCP Site Inspection has been completed, the GCP Site Inspection Report will be sent to the inspectee within 10 working days from the date of the last GCP Site Inspection. It should be noted that the factual matter contained in the GCP Site Inspection Report relates to observations noted during the inspection process.
The inspectee should submit a Corrective Action and Preventive Action (CAPA) Plan to HSA within 30 working days of receipt of the GCP Site Inspection Report.
Once the CAPA is deemed to be adequate, the Compliance Inspector will send a GCP Site Closing Letter. It is important to note that the GCP Site Closing Letter should not be taken as implying a satisfactory state of affairsa in documentation, premises, equipment, personnel or procedures not examined during the inspection.
The inspectee should submit a Corrective Action and Preventive Action (CAPA) Plan to HSA within 30 working days of receipt of the GCP Site Inspection Report.
Once the CAPA is deemed to be adequate, the Compliance Inspector will send a GCP Site Closing Letter. It is important to note that the GCP Site Closing Letter should not be taken as implying a satisfactory state of affairsa in documentation, premises, equipment, personnel or procedures not examined during the inspection.
Common GCP Inspection Findings
The Common GCP Inspection Findings from 2011 and case studies based on some of these GCP Inspection Findings were shared with various stakeholders at the Combined CRP-CRCS Forum held on 12 Dec 2011.
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Newsletter - From the GCP Inspector's Desk
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