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Medicinal Products and Medical Devices in Clinical Trials Conduct and Disclosure

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Medicinal Products and Medical Devices in Clinical Trials Conduct and Disclosure Medicinal products and medical devices in clinical trials condduct and disclosure – and ndever the twain shall meet! Raquel Billiones 1 and Kathy B. Thomas 2 Despite some fundamental differences, 1 Takeda Pharmaceuticals, Zurich, Abstract similarities and overlaps in the requirements Switzerland “Medicinal products and medical devices are and details between the CTR and MDR are 2 Medical & Scientific Writing & Publication different species…they live in parallel evident. There is also a clear aim for the Services, Meersburg, Germany universes” according to a medical device electronic databases, as described in the two expert. But is it really so? This article regulations, to be interoperable. This high - challenges that notion by comparing the level comparison of the CTR and MDR Correspondence to: Clinical Trial Regulation EU No. 536/2014 shows that while the requirements of the two Raquel Billiones (CTR) and the EU Medical Device regulations have been aligned and are very [email protected] Regulation 2017/745 (MDR) in the context similar, their impact on the respective of clinical studies and public disclosure. industries is quite different. Two parallel universes years, we already switch between these universes pharmaceutical industry. The major changes “WARNING : Medicinal products and medical and firmly believe that linking these two is not were the centralised clinical trial application, the devices are different species. They live in parallel only feasible but also profitable, as other increased disclosure requirements, and the universes. They may appear similar (“medicinal colleagues can also attest. 2 Nevertheless, the setting up of a new EU portal and database (to products”), but they are not. Carelessly switching school of thought that “a drug is a drug, replace the existing ones). between universes may be deadly .” These a device is a device, and never the twain shall In 2017, the EU Medical Device Regulation words are taken from a presentation by Ronald meet” is relatively widespread. 3 2017/74 5 (henceforth referred to as MDR) was Boumans, a Senior Regulatory Consultant at released. Literally “left to its own devices till Emergo Group. 1 Jokes aside, after evaluating the Two universes, two regulations now”, 3 the medical technology industry struggles two regulations, we are compelled to challenge In 2014, the Clinical Trial Regulation European with the drastically increased and unfamiliar this statement. As professional regulatory Union (EU) No. 536/2014 4 (henceforth regulatory requirements of this legislation. 6,7 medical writers who have been developing referred to as CTR) was released. The detailed Following the thread of Bouman’s analogy, it felt regulatory documents for both pharmaceutical requirements and documentations of this like aliens had invaded the medical device drug products and medical devices for many legislation were really nothing new for the universe. 74 | June 2019 Medical Writing | Volume 28 Number 2 Billiones and Thomas – Medicinal products and medical devices in clinical trials conduct and disclosure As professionals working for the two transparent, predictable, and sustainable regu - needed for approval of a new device than for a industries, we were obliged to familiarise latory framework for medical devices which new medicinal product. 3 ourselves with these two new legislations. This ensures a high level of safety and health whilst article makes a high-level comparison between supporting innovation [and] to ensure the Clinical study registration the CTR and the MDR (Table 1) based on the smooth functioning of the internal market as Both CTR and MDR require registration of original texts of the legislations and the authors’ regards medical devices . .” 5 clinical studies in a publicly accessible registry. interpretation of those texts built on their The other important difference is that under Each study must be identified with a unique ID experiences of working in the pharma and the CTR, the EMA (“the Agency”) has the major number. This requirement was already covered in medical device industry. The comparison is responsibility of implementation, with support the previous legislation for medicinal products focused on the conduct and disclosure of clinical from the European Commission (EC) and the but not in the predecessors of the MDR. studies, often referred to as clinical trials for member states. For the MDR, the major In the USA, the database ClinicalTrials.gov medicinal products and as clinical investigations responsibility of the implementation lies with the provides a clear breakdown of clinical trials by for medical devices. EC, working together with the competent drugs, biologics, surgical procedures, and devices. authorities of the EU member states. To date, this kind of breakdown of clinical studies Obvious differences is not readily available for studies performed in The most obvious difference is the scope of the Similarities and overlaps the EU or the states of the EEA in the current two regulations. The CTR, as its name implies, The MDR and CTR were written three years database, the EU Clinical Trials (CT) Register. covers interventional clinical trials for medicinal apart and our initial reaction when we first read Currently, the EU CT Register requires only products and supersedes Directive 2001/20/EC the MDR was that the two universes are coming registration of medicinal products tested in and Paediatric Regulation (EC) No. 1901/2006. together, especially when it comes to clinical interventional clinical trials with at least one trial The purpose of the CTR is to add clarity to the study conduct, reporting, and disclosure, as site in the EU/EEA and “does not provide previous laws as well as simplify and harmonise summarised below and also in Table 1 (that information on clinical trials for surgical the administrative processes for clinical trials compares the CTR and MDR). procedures, medical devices, or psycho - performed in the EU/European Economic Area therapeutic procedures”. The MDR may resolve (EEA). Other regulatory aspects of CTR, such Clinical study conduct this information gap, as discussed in the as market authorisation and pharmacovigilance, Clinical evidence is needed for new health following sections. are covered by the Directive 2001/83/EC and products to be granted market access. Clinical Regulation 726/2004. studies (trials or investigations) are performed to The electronic systems and databases The MDR, on the other hand, has a much collect data on efficacy and safety of the tested To support the CTR harmonised approach to broader scope than the CTR and goes beyond products. The CTR and MDR are relatively submission, assessment, and reporting of clinical clinical investigations by including manu - aligned in their definitions of clinical trials and trials, the EC has mandated the EMA to establish facturing, market access, and post-market investigations, respectively, as well as in respect a new EU portal and database according to the vigilance. MDR supersedes two Directives, of the key involved stakeholders (Table 1). specifications in the CTR. Data submitted 90/385/EEC (active implantable devices, 2007) In some cases, the terminologies used differ through the new portal will be stored in an EU and 93/42/EEC (other devices, 2007). The main slightly while the definitions are almost identical. database that is open to the public. Duplications objectives of the MDR are “to establish a robust, In general, it seems that fewer clinical studies are with the existing databases (Eudravigilance and www.emwa.org Volume 28 Number 2 | Medical Writing June 2019 | 75 Medicinal products and medical devices in clinical trials conduct and disclosure – Billiones and Thomas Table 1. Comparison of the requirements for clinical trials/investigations conduct and disclosure under the CTR 536/2014 and MDR 2017/745 EU CTR 536/2014 EU MDR 2017/745 Full name Regulation (EU) No 536/2014 of the European Regulation (EU) 2017/745 of the European Parliament and of the Council Parliament and of the Council of 16 April 2014 on clinical of 5 April 2017 on medical devices, amending Directive 2001/83/EC, trials on medicinal products for human use, and repealing Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and Directive 2001/20/EC repealing Council Directives 90/385/EEC and 93/42/EEC Scope Clinical studies in medicinal products: Clinical studies in medical devices: submission, assessment, submission, assessment, notification, disclosure notification, disclosure (Article 62, Annex XV) Manufacturing, CE-marking (market authorisation), post-market surveillance of medical devices Definitions of Clinical study a: any investigation in relation to humans Clinical investigation : any systematic investigation involving one or terms related to [intended to study clinical, pharmacological, pharma - more human subjects, undertaken to assess the safety or performance clinical studies codynamic effects, identify any adverse reactions, study of a device (per CTR or MDR) absorption, distribution, metabolism and excretion] … with the objective of ascertaining the safety and/or efficacy of those medicinal products Investigational medicinal product : a pharmaceutical Investigational device : a device that is assessed in a clinical form of a medicinal product which is being tested or used investigation as a reference, including as a placebo, in a clinical trial Protocol : a document that describes the objectives, Clinical investigation plan : a document that describes the rationale, design,
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