Postauthorization Changes to Specific Obligations of Conditionally Authorized Medicines in the European Union:
Lourens T Bloem1,2, Aukje K Mantel-Teeuwisse1, Hubert G M Leufkens1
1Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Abstract:
When medicines are granted a Conditional Marketing Authorisation (CMA) in Europe, specific obligations are requested to obtain comprehensive data on benefits and risks. We performed a retrospective cohort study to characterize obligations, examine changes to their description and due dates after initial authorization, determine timing of data submission relative to due dates, and identify drug-related, procedure-related, and obligation-related factors associated with change. We identified 69 obligations for 26 medicines conditionally authorized between 2006 and 2016. We found 39 changes to 27 obligations (39% of obligations), of which four substantially changed the obligation. For 55% of obligations, data submission was delayed. Eleven factors were associated with change, including the use of CMA as a rescue option. The results are potentially indicative of a continuous search by regulators to reduce uncertainties. Submission delays impact public health negatively by prolonging exposure of patients to unknown risks, particularly when the level of uncertainty is high.
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