04 Oct 10 critical findings from 7 sponsor GCP inspections
The Medicines and Healthcare products Regulatory Agency (MHRA) has issued its annual GCP inspections metrics report for the 12-month period from 1.Apr.2016 to 31.Mar.2017.
Of 15 sponsor inspections, all sponsors had at least one major and/or critical finding. This is higher than in the previous 12-month period. There were 10 critical findings from 7 sponsors. Below is a short summary of these critical findings:
- Unapproved updated Reference Safety Information (RSI) was used for adverse drug reaction (ADR) expectedness assessment.
- The use of unapproved RSI meant that pharmacovigilance activities were not conducted in accordance with the clinical trial authorisation (CTA).
- The authority approved RSI in effect at the time of several Serious Adverse Events was not used for expectedness assessments, leading to the underreporting of several Suspected Unexpected Serious Adverse Reactions (SUSARs) and inaccurate information in DSURs.
- Updated documents containing new expected adverse reactions that had not previously been approved as substantial amendments were used for expectedness assessments.
- The use of the wrong terms for expectedness assessment at the start of the reporting period resulted in potentially erroneous Development Safety Update Reports (DSURs) being submitted to the MHRA.
Trial Master File (TMF)
- Documents were not filed in the eTMF consistently or correctly and many were missing.
- The eTMF contained duplicate documents, blank/incomplete documents, errors in document files names and file location, etc.
- The monthly quality control check of all eTMFs was not performed at study level, as required by the eTMF management SOP.
- The audit trails for 5 eTMFs indicated that a large number of documents had been uploaded following the inspection notice, suggesting that the eTMFs were not being updated regularly or kept in an inspection-ready state.
- A paper TMF presented for inspection did not contain all the essential documents required to enable the reconstruction of trial events and demonstrate compliance with the regulations and the organisation’s own quality system.
- Data integrity could not be confirmed because questionnaires being used to evaluate eligibility and primary endpoint data contained language and medical terms that were not easily understood by patients. The questionnaires should have been completed by a healthcare professional, but no clear instructions or training were provided to sites on questionnaire completion. Thus, the accuracy and quality of the data could not be confirmed.
- Incorrect eDiary data were used for the analysis. There was no audit trail to verify when entries were made in eDiary devices and by whom.
- The portal used to manage Data Change Forms (DCF)s did not have an audit trail, so if changes were made to a request after it was submitted by the investigator, these could not be identified.
- The investigator lost control of data between database lock and pdfs being sent to the site; the pdfs reflected the final version of the data and did not contain all metadata.
- The sponsor failed to ensure sufficient and robust monitoring of the trials, leading to data integrity issues in both. Extensive issues and non-compliance with GCP were attributed to deficiencies in sponsor oversight and monitoring processes.
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