Annual Report of the GCP Inspectors' Working Group

The Good Clinical Practice (GCP) Inspectors' Working Group (IWG) published their annual report. The document is the sixteenth annual report of the GCP IWG.  

Scope of the Report

The data in the latest report relates to GCP inspections carried out in 2023. In total, 67 site inspections (including 58 routine and 9 triggered) were requested by the CHMP (Committee for Medicinal Products for Human Use) and carried out by the inspectorates of the Member States. Several inspections requested in 2022 were conducted in 2023, which are therefore included in the report. Most of the inspections were conducted at clinical investigator sites, followed by sponsors and analytical laboratories.

Categorization of Findings

A total of 720 deficiencies, comprising 36 critical, 336 major and 348 minor findings were recorded during the GCP inspections. Some of the examples of common areas of critical and major findings in the subcategories of the three main categories "General", "Trial Management", and "Investigational Site" are listed below.

General
Contracts/Agreements

• Lack of /unclear documentation of duties/tasks delegated to service providers by the sponsor.
• Lack of contracts/agreements between the investigator and facilities involved in the trial.

Essential Documents & Direct Access to Data

• Lack of inspection readiness: Limitations in eTMF (electronic Trial Master File) access.
• Limited access or lack of access to medical records of trial participants for monitors.
• Insufficient assessment of the suitability of storage locations of essential documents.
• Deficiencies in maintaining essential documents (e.g., missing documents, location of documents (including source data) not defined).
• Lack of access at the trial site to trial relevant electronic systems containing essential documents/data.

Facilities and Equipment

• Facilities not suitable for trial procedures.
• Lack of or insufficient assessment of the suitability of facilities for trial procedures.
• Lack of calibration documentation for the equipment used in the trial.
• Long term archiving facility not suitable to prevent premature destruction of clinical trial documentation.

Organisation and Personnel

• Deficiencies in delegation of trial related tasks (e.g., persons not delegated to perform trial related tasks involved in the trial).

Qualification/Training

• Lack of documentation (e.g. training records, training certificates, etc.) evidencing site personnel training in GCP and trial relevant documents.
• Incomplete documentation of qualification, delegation, and training of trial staff.

Randomisation/Blinding/Codes

• Potential bias due to unblinding (e.g., unblinded pharmacy activities and blinded clinical activities monitored by the same monitor).

Standard Operating Procedures (SOPs)

• Lack of SOPs for the development of essential trial documents.
• Deficient process to select, review, and approve SOPs for critical trial related processes.

Trial management
Audit

• Lack of independent quality assurance (QA) personnel available for the study. Deficiencies in the performance of routine QA activities (e.g., no audits conducted of partners/vendors engaged in activities on behalf of the sponsor).

Data Management

• Insufficient communication lines between trial sites and service providers to ensure good communication and quick solving of issues with regard to data handling processes.

Monitoring

• Monitoring procedures failed to detect protocol deviations, reconcile Investigational Medicinal Product (IMP) accountability, manage issues detected in Source Data Verification (SDV) and Informed Consent (IC) processes.
• The protocol was lacking important information about the methods for the recording, reporting, and assessing trial data.
• Discrepancies between protocol and eCRF (electronic Case Report Form) design. Protocol amendments not implemented in the eCRF.

Statistical Analysis

• Lack of a statistical analysis plan.
• Deficiencies in the documentation of data extraction from the eCRF for reporting in the final CSR (Clinical Study Report).
• No QC (Qality Control) performed on the final data analysis.

Investigational Site
Protocol Compliance

• Compliance with the study protocol was not sufficient (e.g., large number of protocol deviations related to IMP administration).
• Protocol deviations relevant to participant safety (e.g., compliance with trial treatment could not be verified from the documentation).
• Deficiencies in the safety reporting process at the site leading to underreporting of AEs (Adverse Events) and SAEs (Serious Adverse Events).
• Protocol deviations approved prospectively, and eligibility waivers granted by the sponsor.

More information is available in the Annual report of the Good Clinical Practice Inspectors Working Group 2023 published on EMA's GCP IWG website.