Clear and clinical? An overview of the new EU regulation for clinical trials

Bruno Speder, head clinical regulatory affairs & consultancy, SGS Life Sciences, gives an overview of new EU regulation 536/2014, introduced to provide a single European submission and approval procedure for clinical trials, and discusses the effects it may have on the performance and reporting of early phase clinical trials.

EU regulation 536/2014 has been enacted to provide a new authorisation procedure for clinical trials in Europe. It will enable a single integrated regulatory authority and ethics committee submission for new investigational medicinal products to be made via a single European Medicines Agency submission portal.

The new regulation includes a two-step approval process, consisting of assessments of the scientific part of the submission file (part I) and of the local requirements of the application file (part II). The objective of this is to create a more streamlined submission and approval process and timelines for clinical trials while also increasing consistency for safety reporting requirements. Additionally, it will expand the scope of the EU’s EudraVigilance scheme, increase transparency and notification requirements for new drug approvals, and confirm the scope and modified definitions required for low-intervention trials and auxiliary medicinal products.

Online electronic submission of information will make the process simpler, with data and supporting material more transparent and easy to analyse. However, two areas that will be affected are approval timelines and transparency of the required data to be supplied.

Phase I trials

Phase I clinical trials are designed to assess the safety and pharmacokinetics of investigational drug compounds and are conducted over a short time period in healthy volunteers, typically one–two months. Such trials can have very complex designs, are normally performed in a specialised clinical pharmacology unit at a single location, and require extensive logistical and planning procedures. Delays to a regulatory approval could impact heavily on these plans.

Timelines for the review of data from such trials vary across the EU. Drug approval regulations currently in force in Belgium and the UK are very short, and specify a 15-day review period. Under the new regulation, these timelines will — in theory — be aligned with the standard EU timelines, but in practice the timelines for phase I single country trials will remain as is.

Identification and recruitment of suitable clinical trial volunteers can partly be performed using a generic screening process. As the new EU regulation 536/2014 defines the start of a clinical trial as the ‘first act of recruitment’ instead of ‘first patient first dosing’, which could eliminate the possibility of the use of generic screening. The new regulation will allow for alternative ‘start’ procedures to be specified in the clinical trial protocol.

In addition to the notification of the start of a trial, the end of the recruitment period must be specified; as well as the end of the trial, any temporary halts and restarts of the research process, and any early termination of the trial. Serious breaches of regulatory procedures and unexpected events that occur during a trial also need to be reported and any relevant third-country inspection reports that are available must be included in the final report. However, any effects that this new regulation has on timelines for the overall drug development process from discovery to market are likely to be negligible.

Transparency requirements

The EU’s transparency requirements for clinical trials are specifically set out in the regulation along with the form and content of information presented in published documentation. Among other details, this information includes the main characteristics of the trial, identification of the investigational medicinal products, treatment population and number of subjects, inclusion and exclusion criteria, and main objectives and endpoints. A published conclusion of the assessment and decision on the trial is also required, as is any information that has been updated during the trial in respect of the start and end dates of recruitment.

As Phase I trials are conducted with healthy volunteers, and not ‘patients’ as such, an increase in data transparency is not expected to have any effect on clinical trial recruitment. Requiring data transparency this early could deter companies from doing studies in Europe.

Not a lot will change for mono-centred, single country studies in practice. In theory, there will be longer review timelines, however, several countries have indicated that for these types of studies they will keep the currently applicable timelines. The main issue will be the integration of the review by the Ethics Committee and making sure that the assessment is made by people experienced with the specificities of Phase I studies.

The major impact of the new regulation will be the transparency requirements, which will also be applicable to Phase I studies. However, these transparency requirements are not fully compatible with the specificities of Phase I studies and could lead to losing the competitive advantage Europe offers as a place to perform these trials.