Drug and biotech companies cannot replace pivotal clinical trials that are non-compliant with good clinical practice (GCP) standards during the assessment of marketing authorization applications, according to a new position paper from the European Medicines Agency (EMA).
Stressing the importance of GCP compliance, the EMA says it’s an “essential prerequisite” for assessing a medicinal product’s safety and efficacy.
The agency also clarifies that when a study is found to be GCP non-compliant during an inspection, the applicant/marketing authorization holder (MAH) have several options, including commenting on the inspection findings, providing a re-analysis of the data that excludes the non-GCP compliant data, and/or presenting a justification why specific data are actually reliable.
“In case the application contains only one pivotal study which is found to be GCP non-compliant and reanalysis is not provided or not possible, this means that the application no longer contains any pivotal clinical data that can be used to support the safety and efficacy of the medicinal product in the context of the application in question,” EMA says, noting companies can always re-apply for marketing authorization with a new GCP-compliant study.
The position paper comes as the EU and India are locked in a battle over India’s GVK Biosciences and its manipulation of data from clinical trials that resulted in the European Commission’s decision last summer to ban the sale of more than 700 drugs relying on that data.
The Indian government and GVK claim that the commission’s ban was disproportionate and that the drugs have been on the EU market for years without any reported adverse events.
And EMA does offer some additional considerations in its latest position paper for cases where GCP non-compliance of a pivotal trial is detected after a drug is marketed and action on the marketing authorization may be required because the data is unreliable.
“Some other elements should be properly evaluated to respect the principle of proportionality, amongst others the patients’ interest to continue to use the medicinal products at stake and the harm that discontinuing the treatment would entail for them and the possibility for the MAH to provide relevant information confirming the quality/safety/efficacy of the product and the persistence of a positive risk/benefit ratio,” the EMA says, perhaps hinting at the disagreement that has pushed the two sides to suspend trade talks.
Data on GCP Inspections
A review of the most recent EMA GCP inspection data also reveals that the agency is increasingly targeting countries outside the US and EU for data integrity violations.
Of the 57 GCP inspections from 2014, emerging markets accounted for a larger cut of inspections than in previous years, with a higher proportion of visits to the Middle East, Asia Pacific and South America.
When compared to 2013, 2014 inspections in Europe fell 39%, while visits to the US decreased by 43%. However, 10 of the 14 non-routine inspections from 2014 were conducted in the US and EU.
EMA position paper on the non-acceptability of replacement of pivotal clinical trials in cases of GCP non-compliance in the context of marketing authorisation applications