PRINCIPLES OF EUROPEAN GCP INSPECTIONS Clinical Trials Directive 2001/20/EU GCP Inspections � Inspections shall be conducted by the competent authority of the Member State, in whose territory the site to be inspected is located Gabriele Schwarz � They shall be carried out on behalf of the Head of GCP Inspection Services Community and the results shall be mutually German Federal Institute for Drugs and recognised Medical Devices (BfArM) � Inspections in relation to centralized g.schwarz@bfarm.de authorization procedures (Regulation (EWG) Nr.2309/93) shall be coordinated by the Agency REASONS TO PERFORM GCP INSPECTIONS PRINCIPLES OF EUROPEAN GCP INSPECTIONS GCP inspections are routinely performed (cont.) � A Member State may request assistance • to verify that organisations, institutions and facilities from another Member State have quality assurance arrangements in place which � The Commission may request a new inspection ensure the conduct of clinical trials in compliance should verification of compliance with this with applicable regulatory requirements and GCP Directive reveal differences between Member • to ensure that human subjects were protected from States undue hazard or risk during the course of clinical � The Commission or a Member State may trials and that internationally recognized ethical propose an inspection at the trial site and/or the standards were applied sponsor's premises and/or the manufacturer established in a third country • to verify that clinical trial data and results are scientifically valid and accurate REASONS TO PERFORM GCP INSPECTIONS REASONS TO PERFORM GCP INSPECTIONS (cont.) (cont.) • concerns about the credibility and accuracy of the GCP inspection might be triggered due to data e.g. when • the recruitment of subjects from vulnerable groups - the recruitment pattern appears to be unusual or other ethical concerns - the efficacy, biological or safety results are • their importance i.e. for an application for marketing inconsistent with regard to results of other studies authorisation - the results of one site are significantly different from the others • concerns about the investigational medicinal - serious and/or persistent GCP non-compliance was product(s) reported before for the site and/or organisation subject to inspection 1
GOOD CLINICAL PRACTICE TYPES OF GCP INSPECTIONS S P O N S O R TRIAL APPLICATION • Surveillance inspections (national) SUSARs • Inspections in relation to the clinical trial ANNUAL SAFETY REPORTS authorization (national) TRIAL REPORT • Inspections in relation to marketing authorizations TRIAL TRIAL DATA TRIAL (international) DESIGN CONDUCT EVALUATION REPORTING � national marketing authorization procedures � mutual recognition procedures (MRPs) TRIAL AUTHORIZATION � decentralized procedures (DCPs) PHARMACOVIGILANCE � centralized procedures (CAPs) G C P I N S P E C T I O N S COMPETENT AUTHORITY ESTABLISHMENT OF A GCP INSPECTORATE ESTABLISHMENT OF A GCP INSPECTORATE Aspects to be taken into consideration Aspects to be taken into consideration • Implementation of a Quality Management System • Implementation of a Quality Management System • Qualification of inspectors • Qualification of inspectors • Estimation of the number of GCP inspections per year • Estimation of the number of GCP inspections per year • Participation in national and/ or European Working • Participation in national and/ or European Working Groups (i.e. GCP Inspectors Working Group) Groups (i.e. GCP Inspectors Working Group) • Harmonization and Cooperation with other European • Harmonization and Cooperation with other European Member State GCP Inspectorates and regulatory Member State GCP Inspectorates and regulatory bodies (e.g. CTFG, CMDh) bodies (e.g. CTFG, CMDh) • Interfaces • Interfaces ESTABLISHMENT OF A GCP INSPECTORATE QUALITY MANAGEMENT SYSTEM (1) • Definition of tasks and responsibilities German Ordinance on GCP, chapter 15: Inspections • SOPs • The competent authority and the competent • Training Federal authority shall have a carefully designed and correctly managed quality assurance system • QC measures e.g. review of inspection reports which comprises at least the organisation • Internal audits structures, responsibilities and procedures • The quality assurance system shall be fully documented and its ability to fulfil its functions shall be monitored 2
QUALITY MANAGEMENT SYSTEM (3) QUALITY MANAGEMENT SYSTEM (2) EudraLex - Volume 10, Chapter IV GCP-Directive 2005/28/EU • Guidance for the preparation of GCP inspections � Member States shall establish the relevant • Guidance for the conduct of GCP inspections procedures for verification of good clinical practice – Annex I Investigator Site compliance – Annex II Clinical Laboratories � – Annex III Computerised Systems The procedures shall include the modalities for – Annex IV Sponsor and CRO examining both the study management procedures – Annex V Phase I Units and the conditions under which clinical trials are planned, performed, monitored and recorded, as – Annex VII Bioanalytical part, Pharmacokinetic and Statistical Analyses of Bioequivalence Trials well as follow-up measures QUALITY MANAGEMENT SYSTEM (4) ESTABLISHMENT OF A GCP INSPECTORATE (cont. EudraLex - Volume 10, Chapter IV) Aspects to be taken into consideration • Guidance for the preparation of GCP Inspection Reports • Implementation of a Quality Management System • Guidance for exchange of GCP Inspection Reports • Qualification of inspectors • Guidance for the communication on GCP inspections and findings • Estimation of the number of GCP inspections per year • Procedure for standardisation of GCP inspection entries in • Participation in national and/ or European Working EudraCT Groups (i.e. GCP Inspectors Working Group) • Harmonization and Cooperation with other European Member State GCP Inspectorates and regulatory bodies (e.g. CTFG, CMDh) • Interfaces QUALIFICATION OF GCP INSPECTORS (1) QUALIFICATION OF GCP INSPECTORS (2) GCP-Directive 2005/28/EU GCP-Directive 2005/28/EU • Member States shall ensure that inspectors have • Member States shall also ensure that the completed education at university level, or have inspectors have knowledge of the principles and equivalent experience, in medicine, pharmacy, processes that apply to the development of pharmacology, toxicology or other relevant fields medicinal products and clinical research • Inspectors shall also have knowledge of applicable Community and national legislation and guidelines applicable to the conduct of clinical trials and the granting of marketing authorisations 3
QUALIFICATION OF GCP INSPECTORS (4) QUALIFICATION OF GCP INSPECTORS (3) German Ordinance on GCP, chapter 15 GCP-Directive 2005/28/EU • The personnel responsible for carrying out the • The inspectors shall be familiar with the inspections shall be present in sufficient numbers procedures and systems for recording clinical data, and shall be qualified for their duties as well as and with the organisation and regulation of the independent and free from commercial, financial or healthcare system in the relevant Member States other constraints which may affect their decision and, where appropriate, in third countries • The persons shall be given the opportunity to participate regularly in specialist training courses (10 days per year) • The qualifications of the personnel shall be verified. ESTIMATION OF THE NUMBER OF GCP ESTABLISHMENT OF A GCP INSPECTORATE INSPECTIONS PER YEAR Aspects to be taken into consideration The number of GCP Inspections to be performed • Implementation of a Quality Management System depends on • Qualification of inspectors � the number of national clinical trials per year • Estimation of the number of GCP inspections per year � the number, type and GCP experience of institutions involved in the conduct of clinical • Participation in national and/ or European Working trials (sponsor sites, CROs, phase I units, Groups (i.e. GCP Inspectors Working Group) clinical sites, laboratories…) • Harmonization and Cooperation with other European � the number of marketing authorization Member State GCP Inspectorates and regulatory procedures with involvement of the national bodies (e.g. CTFG, CMDh) agency • Interfaces (NPs, MRPs, DCPs, CAPs) ESTIMATION OF THE NUMBER OF GCP ESTABLISHMENT OF A GCP INSPECTORATE INSPECTIONS PER YEAR Aspects to be taken into consideration CAVE! • Implementation of a Quality Management System GCP Inspections are • Qualification of inspectors � only partly self-initiated but partly externally • Estimation of the number of GCP inspections per year requested • Participation in national and/ or European Working � only partly voluntary but partly triggered Groups (i.e. GCP Inspectors Working Group) • Harmonization and Cooperation with other European Member State GCP Inspectorates and regulatory bodies (e.g. CTFG, CMDh) • Interfaces 4
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