Análise dos Alertas Sobre os Dispositivos Médicos Emitidos pela Agência Portuguesa do Medicamento: Delineando o Propósito de Novas Recomendações Regulatórias

Introduction: Medical devices are healthcare technologies with a significantly growing market worldwide. This study aims to analyze medical device alerts issued by the Portuguese Medicines Agency, INFARMED, I.P. during 2017, as well as to identify the respective regulatory actions and to suggest additional recommendations. Material and Methods: All alerts on medical device alerts publicly available in the website of INFARMED, I.P. were identified and analyzed, including actions taken. Additionally, reports on medical devices from the Portuguese national competent authorities were compared with reports from other European Union member states such as Germany. Results: A total of 32 safety alerts were identified: 18 (56%) related with devices without identified records of commercialization in Portugal, six (19%) related with devices voluntarily withdrawn from the market, such as counterfeit products, and eight (25%) categorized as ‘other’. In both Portugal and Germany, 0.28 and 4.53 reports of national competent authorities per million inhabitants were identified, respectively. Diverse regulatory actions were taken, such as six compulsory indications to not acquire or use devices. Discussion: Considering that the European Union is an open market where citizens should have equal access to medical devices, the Portuguese system of medical device safety alerts seems to be functioning normally. The identified safety alerts seemed relevant, with Portugal registering a proportionally slightly lower number of alerts when compared with higher sales volume markets, which may be explained by an underreporting of this type of problems. Further studies are needed to confirm these preliminary results, although the development of databases comprising data on patients using medical devices is recommended in order to generate automatic email and text message alerts. Conclusion: A limited number of safety alerts on medical devices was identified in Portugal, with few reported cases of counterfeit or falsified devices. The Portuguese Medicines Agency contributes to the citizens’ access to quality medical devices, by issuing safety alerts, recommendations and mandatory market withdrawals for unsuitable or unsafe medical devices.Fundação para a Ciência e a Tecnologia (FCT) project UID/DTP/04567/2016.info:eu-repo/semantics/publishedVersio

The European landscape for gene therapies in orphan diseases: 6-year experience with the EMA Committee for Orphan Medicinal Products

In 2000, the European Union (EU) introduced the orphan pharmaceutical legislation to incentivize the development of medicinal products for rare diseases. The Committee for Orphan Medicinal Products (COMP), the European Medicines Agency committee responsible for evaluation of applications for orphan designation (OD), received an increasing flow of applications in the field of gene therapies over the last years. Here, the COMP has conducted a descriptive analysis of applications regarding gene therapies in non-oncological rare diseases, with respect to (a) targeted conditions and their rarity, (b) characteristics of the gene therapy products proposed for OD, with a focus on the type of vector used, and (c) regulatory aspects pertaining to the type of sponsor and development, by examining the use of available frameworks offered in the EU such as protocol assistance and PRIME. It was noted that gene therapies are being developed by sponsors from different backgrounds. Most conditions being targeted are monogenic, the most common being lysosomal disorders, and with a very low prevalence. Generally, adeno-associated viral vectors were being used to deliver the transgene. Finally, sponsors are not frequently using the incentives that may support the development and the reasons for this are unclear

Advancing rare disease treatment: EMA’s decade-long insights into engineered adoptive cell therapy for rare cancers and orphan designation

Abstract Adoptive cell therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has emerged as a promising approach for targeting and treating rare oncological conditions. The orphan medicinal product designation by the European Union (EU) plays a crucial role in promoting development of medicines for rare conditions according to the EU Orphan Regulation. This regulatory landscape analysis examines the evolution, regulatory challenges, and clinical outcomes of genetically engineered ACT, with a focus on CAR-T cell therapies, based on the European Medicines Agency’s Committee for Orphan Medicinal Products review of applications evaluated for orphan designation and maintenance of the status over a 10-year period. In total, 30 of 36 applications were granted an orphan status, and 14 subsequently applied for maintenance of the status at time of marketing authorisation or extension of indication. Most of the products were autologous cell therapies using a lentiviral vector and were developed for the treatment of rare haematological B-cell malignancies. The findings revealed that 80% (29/36) of the submissions for orphan designation were supported by preliminary clinical data showing a potential efficacy of the candidate products and an added clinical benefit over currently authorised medicines for the proposed orphan condition. Notably, in 89% (32/36) of the cases significant benefit of the new products was accepted based on a clinically relevant advantage over existing therapies. Twelve of fourteen submissions reviewed for maintenance of the status at time of marketing authorisation or extension of indication demonstrated significant benefit of the products over existing satisfactory methods of treatment within the approved therapeutic indications, but one of the applications was withdrawn during the regulatory evaluation. This article summarises the key findings related to the use of engineered ACT, primarily CAR-T cell therapies, in targeting and treating rare cancers in the EU. It emphasises the importance of use of clinical data in supporting medical plausibility and significant benefit at the stage of orphan designation and highlights the high success rate for these products in obtaining initial orphan designations and subsequent maintaining the status at the time of marketing authorisation or extension of indication