Regulatory Science CBG-MEB

(CAR)-T cell therapies and other adoptive cell therapies are emerging as a promising approach for targeting rare oncological diseases. Development of these therapies is promoted by an orphan designation. A recently published article has examined how these therapies have evolved, based on the European Medicines Agency's Committee for Orphan Medicinal Products (COMP) review of applications evaluated for orphan designation and maintenance of the orphan status for approved medicines which allows for a 10-year period of market exclusivity. The article with first author Maria Elisabeth Kalland is the work of EMA staff and COMP members, including the former chair and MEB colleague Violeta Stoyanova-Beninska. It emphasizes the importance of sufficient data in support of preliminary evidence for efficacy and of the significant benefit criteria. Because of the specificities of the adoptive therapies, (early) clinical data has been provided and is critical for a successful orphan designation and approval as an orphan medicine. https://lnkd.in/eKA5Jd4a Tomas Pose Boirazian Frauke Naumann-Winter enrico costa Dinah Duarte Eva Malikova Dinko Vitezic Kristina Larsson Armando Magrelli Segundo Mariz Gloria Palomo Carrasco Darius Matusevicius #OrphanDesignation #CarTCellTherapies #RegulatoryScience

Rare diseases affect up to 36 million people in the European Union, yet only 5-10% of these diseases have treatment options. To stimulate the development and authorisation of medicines for rare diseases (‘orphan conditions’), the European Commission can grant orphan designations. But how well do current disease terminology systems map these orphan conditions and therapeutic indications? In order to enable systematic evaluation and communication of the diseases for which designated orphan medicines have (not) been developed and authorised, former MEB-intern Keerti Jadoenathmisier and co-authors investigated the feasibility of important disease terminology systems for mapping orphan conditions and therapeutic indications. The results of this collaborative project, led by the Dutch Medicines Evaluation Board and Utrecht University, are now published in the European Journal of Pharmaceutical Sciences. Six major disease terminology systems (ICD-10, ICD-11, MedDRA, MeSH, Orphanet nomenclature of rare diseases, and SNOMED CT) were assessed for mapping of designated orphan medicines authorised during 2022-2023. The findings showed that SNOMED CT had the highest coverage, but other systems such as the Orphanet nomenclature of rare diseases, MedDRA, and ICD-11 also performed well when considering synonyms and partial matches. Read the paper here: 🔗 https://lnkd.in/eezdEjus Lourens Bloem, Inge Soons, Violeta Stoyanova-Beninska, Bert Leufkens, Marjon Pasmooij, Utrecht Centre for Pharmaceutical Policy and Regulation #RegulatoryScience #OrphanMedicines #RareDiseases

Generating Real-world evidence (RWE) to support evaluations by EU regulators and down-stream decision makers has been the focus of a recent pilot by the European Medicines Agency (EMA). In a review article, Stefanie Prilla along with (former) MEB colleagues Violeta Stoyanova-Beninska, Sabine Straus, Peter Mol and Liana Martirosyan present the key-learnings from the pilot and their perspective on how to maximize the potential of regulatory-led RWE generation. The review highlights Real-world evidence (RWE) as a great value for regulatory decisions. Additionally, early interactions between regulators and study requesters are crucial to ensure that research questions are well understood and addressed. Studies using real-world data (RWD) can thus complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This experience paves the way for more effective use of RWE in regulatory processes, ultimately enhancing decision-making in medicine safety and utilization. ➡ https://lnkd.in/eva2iq9m #RealWorldEvidence #RegulatoryScience Sophie Groeneveld, Alexandra Pacurariu, María Clara Restrepo-Méndez, Patrice Verpillat, Carla Torre, Christian Gartner, Frauke Naumann-Winter, Kieran Breen, Nathalie Gault, Sylvie Benchetrit, Brian Aylward, Maura O'Donovan, Jesper Kjær, Peter Arlett

Our colleagues are actively participating in various ways at the FIGON DMD conference these days. Find them today and tomorrow at the parallel sessions on drug repurposing and the new pharmaceutical legislation (Stefan Verweij), or at the following poster presentations: - poster #13 on patient preferences in the context of drug recalls (Pieter Annema) - poster #42 on sustainable drug use (Chaimae Mahtour and Lisa Heltzel) - poster #69 on biomarkers in regulatory decision-making (Audrey Hermans and Lysbeth Bakker). Or catch-up with our other colleagues during the coffee-breaks Ton de Boer, Hemme Hijma and Michiel W. van den Heuvel, MSc and more.   #FIGON @Hyphen Projects #DMD2024  

Decentralized clinical trials (DCT) aim to bring clinical trial activities closer to participants’ homes. For example by using wearables and apps to collect data. Currently, the use of DCT approaches is limited, but explorative research will help to further understand the benefits and should therefore be facilitated. Amos de Jong has explored the opportunities and challenges for DCT approaches in Europe, and evaluated the current use of DCT approaches. On Monday 7 October he defended cum laude his PhD thesis on this subject: ‘Bringing clinical trials home: European regulatory perspectives on decentralized clinical trial approaches‘.   Amos de Jong’s research focuses on innovation in clinical research and its regulatory implications. His project is embedded within the IMI Trials@Home consortium (www.trialsathome.com). During his research, Amos was supervised by prof. Helga Gardarsdottir (Utrecht University), MEB Chair prof. Ton de Boer, dr. Mira Zuidgeest (UMC Utrecht) and dr. Yared Santa Ana Téllez. DCT approaches were permitted and supported by guidance from health authorities during the COVID-19 pandemic. Amos: “Through interviews, various actors involved in assessment of clinical studies and medicines reported that DCT approaches have the potential to reduce the burden for participants. These approaches increase the applicability of trial results, because data is collected in settings that better reflect the real world. On the other hand, participants may experience more difficulty because of limited ability to use digital devices or more responsibilities related to obtaining study measurements.” Amos thesis is still under embargo, but his published work can be found here: https://lnkd.in/eVVakcwf. The MEB congratulates Amos on his new Dr. title! Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University

Paediatric drug development currently relies profoundly on clinical trials, which are often limited by small sample sizes due to ethical and logistical challenges in study design. Modelling and simulation approaches have the potential to optimise paediatric trial design. For example, through extrapolation of adult data, determining appropriate sample sizes, and establishing accurate dosing regimens. In July this year, Loes Maton started a PhD project on the use of modelling and simulation in paediatric study design. “The limited availability of data introduces uncertainty in the validation of pharmacokinetic models. As a result, the predictive power of these pharmacokinetic models can be compromised, leading to uncertainty in key parameters such as dosing, efficacy and safety. By advancing my understanding of how modelling and simulation can contribute to paediatric study design, my PhD project has the potential to improve the efficiency and ethical standards of clinical trials in children.”   Her supervisory team consists of Pieter Colin, Flora Musuamba, Jeroen Koomen and Pyry Välitalo. Loes' PhD project is part of the Horizon-funded project ERAMET (https://lnkd.in/eBj9w7XY), in which 17 partners from 7 countries participate. Next to the MEB, three other medicines agencies participate in this project, FAMHP (Belgium), AEMPS (Spain) and ANSM (France).   Loes completed a Master’s degree in Bio-Pharmaceutical Sciences and a second Master’s degree in Science Communication for Design and Innovation. She was an intern at the communications department of the MEB during the COVID pandemic. “The communication department at MEB sparked my enthusiasm for the organisation. However, after my studies, I wasn’t quite ready to leave the field of research and/or pharmaceuticals just yet. Therefore, I decided to apply for the position of clinical pharmacokinetics assessor.”   In the coming 5 years Loes will dedicate 50% of her time to her PhD project, and will work 50% of her time as a clinical pharmacokinetics assessor. This connection between science and the regulatory work, will make sure that the knowledge obtained in the ERAMET-project, will directly impact the assessment work.   Good luck with your PhD project, Loes!

Advanced therapy medicinal products (ATMPs) are complex pharmaceuticals with high human specificity. Since the clinical relevance of in vivo non-clinical data is limited by species differences, our colleague Hsiao-Tzu Chien investigated how a human-centric safety assessment of ATMPs can be achieved.   To answer this question, Tzu and her colleagues interviewed 17 stakeholders from 9 different countries who were involved in ATMP development. The interviewees were asked for their perspective on the use of in vivo studies, the perceived hurdles on this topic and the associated potential solutions regarding non-clinical development of ATMPs. Furthermore, a workshop was held with key stakeholders to further discuss major topics that were identified during the interviews.   Based on the interview data and the workshop discussion, conducting in vivo studies remains the status quo for ATMP development. The main identified hurdles were: 🔹 Determining the amount of non-clinical data required before First-in-Human studies. 🔹 Discordance between different regulatory agencies. 🔹 No clear guidance on the use of in vitro assays. 🔹 Effective use of limited patient samples to understand a treatment or for clinical monitoring.   Defining the need for future in vivo studies as well as improving the implementation of a New Approach Methodology (NAM)-based approach, will require data transparency, understanding of the added value of in vivo studies, and continuous advancement, evaluation, and qualification of NAMs.   Tzu and her colleagues established a roadmap that demonstrates the practical steps towards a human-centric safety assessment of ATMPs. Do you want to find out more? Access the paper here: https://lnkd.in/er82gUiu   #3Rs, #ATMP, #InVivoStudies #Regulatory #Nonclinical Victoria de Leeuw, Joantine van Esterik, Frans Russel, Anne Kienhuis, Peter Theunissen, Peter van Meer

A recent paper co-authored by MEB colleague Carla Jonker and MEB board member Annet Bosch, describes a framework for multistakeholder patient registries in the field of rare diseases. In the field of rare neurogenetic diseases this is the first framework that describes recommendations for new and existing patient registries to address challenges and to maximize their impact on care, research, drug development, and regulatory decision making. The development of the framework consisted of a 3-step process that started with 1) a literature study and qualitative research to extract guidance and practices. In addition, 2) representatives of 5 international rare neurogenetic diseases registries were interviewed, which added learnings from hands-on experiences to the framework. During 3) a digital multistakeholder focus group input from experts was collected to refine the framework. Key principles of the framework include that data should be rapidly accessible, independent, and trustworthy. The data should be highly descriptive and accessible through a shared infrastructure and not spread over multiple isolated repositories. Sustainable and independent financing of registries is important but remains challenging because of lack of widely supported funding models. This framework will guide stakeholders in establishing or improving rare disease registries. Still there is a need for more clarity regarding quality requirements for registries in regulatory and HTA context. https://lnkd.in/eGFGHuW3 #NeurogeneticDisease #PAtientRegistries Daphne Schoenmakers Sibren van den Berg Lonneke Timmers Laura Adang Marc Van de Casteele Mareen Datema Mariëtte Driessens Holm Graessner Valerie Greger Günter Höglinger Hannerieke van den Hout Mirjam Langeveld Marjo van der Knaap Kelly Brown-Plueschke Sanne van Rijn, MSc. Elise Saunier Vivar Carla Hollak Wim Goettsch Nicole Wolf  

In 2010, new European pharmacovigilance legislation was proposed for the European Union which came into effect in 2012, also leading to the installment of EMA’s Pharmacovigilance Risk Assessment Committee. In a recent scientific publication, a group of authors including MEB colleague and former PRAC chair Sabine Straus, reflected on the strengthened EU system for pharmacovigilance. They conclude that the legislation achieved its aim to strengthen patient and public health protection. The authors also set out a vison for the future, based on four principles to further progress the EU pharmacovigilance system: a compass to guide actions to build capacity, technology and methods and to improve regulatory processes. More in the article - The STAR Compass to Guide Future Pharmacovigilance Based on a 10-Year Review of the Strengthened EU System #regulatoryscience #pharmacovigilance Priya Bahri Georgy Genov Peter Arlett Viola Macolic Sarinic Evdokia Korakianiti Alexis Nolte Martin Huber https://lnkd.in/e9PcWVZJ

  Artificial Intelligence (AI) and computer modelling in pharmaceutical manufacturing is one of the major innovations in (pharmaceutical) manufacturing. Marcel Hoefnagel (Quality Assessor at the MEB and Chair of the EMA Quality Innovation Group) has recently co-authored a paper with FDA and EMA colleagues on regulatory aspects of their use. ChatGTP has recently put AI and computer-based knowledge engineering in the public spotlight. However, computer-based modelling and machine learning are already used in engineering over the last decade. Process models are a growing tool for pharmaceutical manufacturing process design and control. Tools such as AI might accelerate pharmaceutical processes. There are already several examples of process improvements realized through the application of process models. An important regulatory consideration of using a process model is the risk of potential impact on the quality of the product in case model predictions are inaccurate, also in case the model is adapted after process changes. This paper discusses existing risk-based frameworks for model validation and lifecycle maintenance that could aid the adoption of process models in pharmaceutical manufacturing.   #regulatoryscience #artificialintelligence #pharmaceuticalmanufacturing   https://lnkd.in/etcVf2en