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EU Regulatory Strategy for Clinical Trials

Written by ProPharma Staff | December 22, 2021

Setting up a clinical trial in the European Union (EU) has historically been an expensive and time-consuming business. With 27 individual member states each requiring its own review and approval, it has not always been an enticing option for Sponsors. However, with the implementation of the new Clinical Trial Regulation and Clinical Trial Information System, this is set to change.

What are the standard Clinical Trial phases?

Phase I

Phase I studies may also be known as First in Human studies. This is the first time that the Investigational Medicinal Product (IMP) will be used in humans, usually healthy volunteers. These studies are used to show that the IMP is safe for use in humans.

Phase II

Once the IMP has completed Phase I studies, the Sponsor can move on to Phase II. Phase II studies are usually the first time that the IMP will be used in patients – participants who have the disease or condition. These studies are used to show that the IMP is safe and effective (i.e. it treats the intended indication). These studies are also known as Proof-of-Concept studies.

Phase III

Phase III studies are usually larger studies and may also be referred to as pivotal studies – they will provide the key data for a future Marketing Authorisation Application (MAA) in the EU. They will typically compare the IMP against the current Standard of Care (SoC) or other approved medicinal products on the market. Generally, these trials will be randomised and blinded.

Phase IV

Also known as postmarketing surveillance trials, these are started once approval has been granted and are used to look at the long-term side effects of a drug. These trials are most commonly requested by the regulators as conditions to granting drug approval.

Additionally, Sponsors may choose to combine two phases of a trial, for example they may decide to start a Phase I/II or a Phase II/III trial. These combination studies can save the Sponsor time and money, but they may require more (and earlier) collaboration with regulators in order to gain approval to start the trial.

What legislation governs Clinical Trial Applications in the EU?

As of 31st January 2022, the European Union will move from being governed under the Clinical Trial Directive to the Clinical Trial Regulation (CTR). This new regulation means that Sponsors can make one single application to all EU member states and receive a single decision that covers both Health Authorities (Regulatory Agencies) and Ethics Committees.

In order to facilitate this, the European Medicines Agency (EMA) has set up a new Clinical Trial Information System (CTIS) – a platform that is used by Sponsors/Contract Research Organisation (CROs) and member states. The combined review happens in two parts: Part I and Part II.

  • Part I is a review of the dossier by each applicable member state. This review is led by the Reporting Member State (RMS), who consolidates review comments from each member state concerned (MSC) – this is comparable to the Health Authority review. There will be one conclusion given at the end of the Part I review.
  • Part II is a review of the dossier by each member state against national regulations – this is comparable to Ethics Committee review. Each MSC will produce a Part II conclusion.
  • Once the Part I and Part II conclusions have been reached, each MSC will combine the Part I and Part II conclusion and will release a National Decision.

There are two important notes to mention:

  1. It has been stated by the EMA that in most cases, the Health Authorities and Ethics Committees will review both the Part I and Part II parts of the dossier in order to produce a more harmonized outcome.
  2. During the review, if a MSC does not review in time, or acknowledge the procedure, then the conclusion reached in Part I will be the decision of the member state for authorization of the clinical trial.

This new system will create a more streamlined review and approval process which will ultimately lead to a faster and smoother clinical trial start up pathway. This will make the European Union member states a more attractive market when Sponsors are considering sites.

What do Sponsors need to include in their Clinical Trial Application (CTA) dossier?

There are some standard documents that are required for all CTAs, regardless of phase or type of IMP. These include the following:

  • Protocol
  • Investigational Medicinal Product Dossier (IMPD)
  • Related IMPD documents – GMP Certificates, Manufacturer/Importer Authorisations, Qualified Person (QP) Declaration
  • Investigator’s Brochure (IB)
  • EudraCT number and form – EU Application Form
  • Participant Information Sheet and Informed Consent Form (PIS/ICF)
  • Contract and Budget templates
  • Summary of any Scientific Advice procedures
  • Summary of any Paediatric Investigation Plans related to the IMP

If this seems daunting, know that ProPharma has extensive experience in the drafting of these documents so that they meet EU guidelines, and our experts are available to provide support.

In parallel to the drafting of core documents, a review of local guidelines/legislation is conducted. For example, most member states will require a copy of the Principal Investigator’s CV and Good Clinical Practice course certificate. Additionally, some member states may have other local documents such as site suitability forms, financial disclosure forms etc. Furthermore, each member state may have their own PIS/ICF templates or guidelines – the core PIS/ICF should be tailored to each member state’s guidance/templates and should also be in each member state’s local language. ProPharma can manage the full translation process of all required documents.

Contact ProPharma for Expert Guidance

The clinical trial approval process has not always been smooth sailing in the EU. It has taken a long time to implement the new CTR and CTIS, but 31st January 2022 should herald a new beginning for a more streamlined and cost-effective approval process, making the EU a leading region for clinical trials.

ProPharma has been very proactive in preparing for these changes and is ready to support Sponsors in this new landscape. Contact us to learn more about our services and get started today!