Annual report of the GCP Inspectors Working Group published

The ninth annual report of the Good Clinical Practice Inspectors Working Group (GCP-IWG) has been published on August 18, 2017. The group has been established in 1997 and focuses on harmonization and coordination of GCP related activities at EU level.

In the period for 2016, the inspectorates carried out a total of 85 CHMP (Committee for Medicinal Products for Human Use) requested inspections, 42% of them conducted in the EU/European Economic Area/European Free Trade Area, 28% in the USA, and 20% in the Middle East/Asia/Pacific. The remaining percentage (10%) of inspections was carried out in South/Central America, CIS, Canada and Africa. Of the 85 inspections 56 were routine and 29 were non-routine inspections. Most of the inspections were conducted at the clinical investigator site (64%) and the sponsor site (20%).

According to the report, EU GCP inspectors found a total of 1033 deficiencies at trial sites worldwide, of which 9% were considered "critical", slightly over half were "major" and just over a third were "minor". Issues included incomplete documentation, discrepancies between source data / data reported in clinical study reports (CSR), and deficiencies in data management and trial monitoring.

By category, most of the deficiencies found were classified as "General", followed by "Trial Management (Sponsor)", "Investigational Site" and others (e.g. "Investigational medicinal products (IMPs)", "Lab/Technical Facilities", "Informed Consent", and "Computer System").
Within the "General" category the following numbers of critical findings have been reported:

• 19 in the area of Essential Documents,
• 4 in Source Documentation and Contracts/Agreements (respectively),
• 2 in Standard Operating Procedures, Qualification/Training, Organization/Personnel, and Direct Access to Data (respectively).

Essential documents issues included lack of records of blood sample shipments and incomplete documentation. Regarding Source documentation inspectors found discrepancies between source data and data reported in the CSR.

The "Trial Management" area saw 11 critical deficiencies in Trial Monitoring, 8 in Data Management, and 1 in CSR. Deficiencies found included inadequate monitoring activities on site, inappropriate systems for reporting protocol violations, relevant information missing in the CSR and inconsistencies between source data / data reported in the CSR. Other deficiencies identified included late introduction of amendments in the study and inadequate design of the study protocol.

Deficiencies identified in the "Investigational Site" area included discrepancies between source data (such as medical history, concomitant medication) and the CRF (Case Report Form) for a sample of subjects, failure to report all adverse events to the sponsor, insufficient maintenance of IMP blinding, and violation of a number of inclusion criteria for some patients.

Beside the CHMP-GCP inspections many others are performed as part of national programs (oversight of the conduct of clinical trials in Europe, marketing authorization applications). In total 459 inspections were conducted in 2016, including the CHMP requested inspections (85). Most of the inspections requested by the CHMP were conducted jointly by inspectors from at least two EU member states. However, 11 were carried out by inspectors from just one country. Observers from non-EU countries are always invited to observe the EU GCP inspections performed in those countries. Of the 49 non-European inspections in 2016, "at least 18 GCP inspections requested by the CHMP were observed by 3rd country regulatory authorities, including Belarus, China, Japan, the Russian Federation, South Africa and the USA", the report says. Furthermore, 5 inspections were performed jointly with the USA.

HOT TOPICS of the GCP IWG SUBGROUPS

• In January 2017 a new set of Questions & Answers has been published on EMA´s website covering contractual arrangements with e-vendors and patients’ data integrity.
• A group contributed to the revision of the GCP inspection procedures and guidance documents, available in EudraLex Volume 10, in order to be aligned with the requirements of the new Clinical Trials Regulation (EU) No 536/2014 (CTR).
• A GCP IWG subgroup worked on the development of the new guideline on "risk-proportionate approaches in clinical trials", which focuses on low-intervention studies and is intended to help implement aspects of the new CTR. The draft guideline has been published in 2016 and a summary of the comments as well as the replies have been available on EMA´s website since August 2017.
• Other subgroups are working on the draft guideline on the clinical trial master file (published for consultation in April 2017) and two documents on serious breaches. The draft guideline for the notification of serious breaches of the CTR or the clinical trial protocol has been published for public consultation in May 2017.
• A GCP IWG subgroup has been involved in preparing the functional aspects of the required EU portal and database, "in particular in relation to gathering the business requirements for the inspection module and working on the process to handle serious breaches to be reported by clinical trial sponsors". According to the report, the inspectors are expected to be involved in a later stage in the testing of the EU Inspection Module. As reported before, the provisions of the CTR are anticipated to take effect in 2019.

Liaison with international partners

The EMA and the U.S. Food and Drug Administration (FDA) have had a collaborative initiative in the area of GCP since 2009, and this has now been extended to the area of bioequivalence, together with some member states, the report notes. The Japanese regulatory agency, the PMDA (Pharmaceuticals and Medical Devices Agency), has officially requested to join the FDA/EMA collaborative initiative. Last year a face-to-face meeting took place to discuss the joining process together with the FDA.

Read more on EMA´s GCP Inspectors Working Group Website.