EMA Clarifies ‘Triggers’ for Routine Versus For-Cause GCP Inspections
As drug sponsors make their way through the EU approval process, there are “triggers” that can help European Medicines Agency inspection coordinators determine whether a clinical trial should undergo a routine or for-cause good clinical practice inspection, an agency working group says. Determining factors include trial size, complexity and site selection.
While every trial could benefit from closer scrutiny via inspection, “this is not feasible and not always necessary,” the EMA’s GCP Inspectors Working Group says in a report posted Aug. 21.
“A GCP inspection is a time and resource consuming process and therefore a request for an inspection should be considered when triggers are identified and [an] alternative method cannot provide the necessary assurance, or when unresolved issues remain” post-evaluation, the group adds.
Routine GCP inspections, carried out in the absence of a specific trigger or concern, “should have a random element in that not all [marketing authorization] applications would necessarily give rise to a GCP inspection,” the report states. But there are numerous factors that underscore the need for a routine GCP inspection and the agency should be aware of these. They include:
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There are inconsistencies in an application dossier or missing GCP-related documents;
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The candidate being studied is a recombinant product, monoclonal antibody, cell therapy, gene therapy, new chemical entity, blood product or orphan drug;
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The applicant is not the sponsor of the proposed trial;
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The trial supports a sponsor’s first marketing authorization application; or
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The scope of a supporting trial is unusually minimal.
Pivotal trials “will usually be the ones selected” for routine GCP inspections, the working group says. But if more than one is planned, trial size, complexity, design and site selection will all be taken into consideration when determining inspection priorities.
When making determinations about possible for-cause inspections, requested by assessors when concerns arise about GCP deviations, the agency should consider many of the same factors that go into routine inspection decisions. However, there are other factors specific to a for-cause inspection request that should be taken into account. Among these are the following:
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There is a lack of information about an ethics review;
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The study’s administrative structure involves an unusually large number of researchers;
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Major changes to study protocol have occurred or troublesome treatment issues emerged;
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There are unexplained differences in the number of patients per treatment arm; or
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Efficacy and safety variables regarding definitions and/or measurements.
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