| dc.description.abstract | Background: The European Medicines Agency (EMA) has implemented a regulatory pathway for the conditional marketing authorization (CMA) of medicinal products. This pathway aims to facilitate timely patient access to treatments for unmet medical needs by accepting less comprehensive data than otherwise required. To obtain a CMA, the applicant must demonstrate a positive benefit-risk balance, fulfilment of unmet medical needs and likelihood that comprehensive data will be submitted post-authorization, and the immediate availability of the product must outweigh the risks associated with non-comprehensive data. To ensure that comprehensive data concerning safety and efficacy are obtained, specific obligations for post-authorization data submission are implemented that are reviewed yearly during annual renewal of the CMA.
Aim: The aim of this study was to investigate the follow-up of specific obligations required for anticancer medicinal products granted a CMA, including their duration, potential changes, and reasons for these changes.
Methods: A retrospective cohort study of specific obligations for anticancer medicinal products granted a CMA between 2006 and 2021 was performed. Data were extracted from the European Commission’s Union Register of medicinal products and confidential EMA assessment reports. The state of specific obligations over time was investigated by following them up from initial authorization until they were fulfilled, the CMA was revoked, or the end of the study period (November 2022). The state of specific obligations was determined by comparing the wording at initial authorization and each follow-up moment (mostly annual renewals) and defined as maintained, fulfilled or changed. Changes were categorized as changes in due date, changes in description, or both.
Results: From 2006 to 2021, 40 anticancer medicinal products were granted a CMA. These products were subject to 92 specific obligations, which were followed for a median 2.5 years (IQR: 1.6-4.4), with the longest follow-up time being 10.7 years for Caprelsa. During follow-up, 245 states were determined. Of these, 140 (57%) comprised maintenance of the specific obligation, 28 (11%) change in due date, 7 (3%) changes in description, 6 (2%) changes in both due date and description and 63 (26%) obligations were fulfilled. Reasons for a change in due date were often enrolment delay. Major changes in description of the SOB were made for Tyverb and Xalkori. Major changes to the marketing authorization were also identified for Caprelsa and Rubraca, leading to a restricted indication of the CMA. Most of the SOBs (67%) with a due date delay of ≥3 years were granted a CMA in 2006-2012. After 2016 no major delays in due date were found at the end of follow-up, the CMA of 24 (60%) anticancer medicinal products were converted to a standard marketing authorization while 1 (3%) was revoked.
Conclusion: In conclusion, despite changes occurring in specific obligations, overall, most of time specific obligations are fulfilled as imposed and within the initially imposed due date. Especially in later years, only few major delays in due date (delay three years or more)/and or description occurred. Also, the time for a CMA to be converted to a standard marketing authorization decreased over time .This suggests that the current systems and procedures in place for managing conditional marketing authorizations are effective in ensuring the ongoing safety and efficacy of these products and may have been become better overtime. | |
