Quantitative trend analysis of well-established use mutual recognition and decentralised products indicates codified disharmonisation in the European Economic Area.

The growing number of well-established use (WEU) applications was reported by the Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh). The procedures from the CMDh annual statistics and products from the Mutual Recognition Information Product Index were analysed between 2006 and 2023. Drop-out and CMDh referral rates were determined, and the Anatomical Therapeutic Chemical codes for WEU products were subjected to trend analysis. The Summaries of Product Characteristics (SmPC) of active substances with a growing interest were scored to determine the level of disharmonisation in the most commonly authorised strength and pharmaceutical forms. The rise in the relative number of WEU applications has been confirmed. The reasons for heightened interest in WEU applications could be explained by (i) the reliable legal basis it has transformed into, (ii) the flexibility, (iii) the incentive system awarding protection. Products containing 3 mg melatonin and 25,000 IU colecaliferol in solid oral forms were the most sought-after products in recent years. An analysis of the SmPCs revealed a significant degree of disharmonisation in the clinical particulars, and it also shed light on intra- and inter- Reference Member State (RMS) variance in the decision making. The current European medicine approval system is not suited to effectively handle this ever-increasing use of one of the most resource intensive legal bases due to the high level of disharmonisation that has been overlooked for years. Consequently, a change in the current application compilation and assessment practices might be beneficial to ensure patient safety and therapy success.