Assessment of medicinal products : a comparative study between Europe and United States of America

Abstract

Differences in evaluation practices during the registration of medicinal products in Europe and the United States of America are found. The aims of this research were to compare the outcomes of the evaluations by the European Medicines Agency (EMA) and the US Food & Drug Administration (FDA) and to highlight differences in the approved product information and the differences in the decision-making process between the two agencies using cardiology-related medicinal products as examples. The method used involved: i) All cardiology-related medicinal products assessed by the EMA (1995-2016) were identified using the Anatomical Therapeutic Chemical (ATC) code and matched with the FDA counterparts using active ingredients, branded names and authorisation holder details; ii) The assessment reports (EMA), the reviews (FDA) and initially-approved product information (EMA & FDA) for each identified drug were obtained; ii) A tool was developed and validated by 6 experts to compare the differences in the outcome of the evaluation between the two agencies. Twenty-seven cardiology-related medicinal products were identified. Mipomersen was the only identified active ingredient with a disagreement in the outcome between agencies. Mipomersen was refused by the EMA and authorised by the FDA. The FDA designated the indication with an orphan designation while the EMA did not and this is considered to be the reason for such a difference in the decision-making process for this product. Fourteen products were found to have different indications when comparing the label (FDA) to the Summary of Product Characteristics (SmPC) (EMA). Differences in the indications have been categorised according to the following restrictions: disease states (5), patient characteristics (4), severity of the condition (3), combination (3), previous therapy failure (1) and inappropriate alternative therapies (1). The EMA and the FDA both contributed to indication restrictions. Different clinical scenarios (4) were identified, where agencies authorised a product for a different clinical setting in view of different efficacy-related clinical studies submitted by the industry. The number of post authorisation requirements, related to safety and efficacy, for the same products were found to be (73) EMA and the (29) FDA. Details in the information included in the product information and label related to efficacy and safety also vary between regulatory agencies for the same product. Lack of harmonisation in the EMA SmPC and FDA label noted in the 26 products studied included differences in indications (18) and safety (21). Post-authorisation requirement differences (25) have been found between the EMA and the FDA. The regulatory agencies and the pharmaceutical industry are both responsible for this lack of harmonisation which may lead to differences in clinical guidelines, pricing policies, and drug use. It is suggested that there is a need of a framework to ensure more collaboration between agencies and industry to reduce discrepancies in medicine regulation.