In vitro diagnostic medical devices (IVDs) are increasingly in demand as the medical technology evolves by leaps and bounds. With the application of the In Vitro Diagnostic Medical Device Regulation (EU) 2017/746 (IVDR) on 26th May 2022, the number of Clinical Performance Studies (CPS) has risen as it allows manufacturers to gather sufficient clinical evidence to meet the regulation’s requirements. Our experts highly recommend that IVD manufacturers carefully plan their CPS activities to avoid delaying their product´s access to the European market.
The present article aims to provide manufacturers with an overview of the Ethics Committee (EC) and National Competent Authorities (NCA) application timelines and requirements in the context of an IVD Clinical Performance Study in Spain, Europe.
IVDR CPS application requirements
A gripping aspect of the IVDR is that each Member State can determine the appropriate authority to assess the CPS application or receive the CPS notification, according to article 67 of the IVDR. Moreover, CPS are subject to scientific and ethical review, the latter of which has to be done by an EC in accordance with national law. The regulation specifies that CPS may only be conducted if an EC has not issued a negative opinion on the study.
Particularly in Spain, NCA approval is only required for interventional studies and those that require surgically invasive sampling or additionally invasive procedures for the purpose of the CPS, according to Article 58 of the regulation. According to the AEMPS, non-interventional studies with IVDs bearing CE-mark will need to be notified to the NCA if one of the following scenarios are present: 1) they involve invasive or burdensome procedures, or 2) they involve diagnostic tests for therapeutic screening that use leftover specimens. On the other hand, EC approval is mandatory for most CPS, regardless of whether them being interventional or not. Their list of requirements is very reasonable, and their path to approval usually requires one round of comments.
Other key considerations for CPS
In addition to the IVDR, manufacturers of IVD planning a CPS should consider ISO 20916:2019. This standard summarizes the good study practice and requirements for conducting a CPS to assess the clinical performance and safety of an IVD, including an overview of the documentation required.
Importantly, ISO 20916 provides further clarification on the differences between non-interventional vs interventional studies, and contains specific guidance to start and conduct a scientifically sound investigation according to the level of risk of the study. It is relevant to highlight that “higher risk” studies are more strictly regulated and therefore, require additional planning time. In contrast, authorities may waive several of the most basic documents we usually find in medical device studies for some non-interventional studies, such as the Informed Consent Form and Insurance Certificate.
If you are interested in obtaining more information about ISO 20916:2019, consider visiting the following link.
Roadmap overview through a CPS start-up process in Spain
The first step towards conducting a study is developing the CPS essential documents (i.e. the Clinical Performance Study plan and summary Informed Consent Form, if applicable), which roughly takes 3 weeks. Said documents are included in the application package to the applicable EC and/or NCA. Following application, the EC and/or NCA reviews the documents and either approves or requests further clarifications or documentation to support the application. It shall be noted that based on site requirements, additional local EC applications may be needed.
In our experience, the EC approval process of a CPS in Spain takes approximately two months from the moment of application until the EC issues a favourable opinion of the study. Meanwhile, NCAs are still transitioning into the CPS processes introduced by the IVDR, and this translates into less clear timelines.
Another relevant milestone in the start-up phase of CPS’ together with NCA/EC applications is the Clinical Trial Agreement (CTA) execution. The CTA is critical for conducting the study and involves several rounds of negotiation between the legal departments of the study site and the Sponsor. This thorough process usually takes two months, or even more! Nevertheless, negotiations can be performed in parallel with the application phase to shorten the timelines in the attempt of obtaining the fully executed CTA by the time the study is approved.
How can AKRN support manufacturers and clients?
AKRN’s clinical team has thorough expertise in designing, conducting, recording and reporting clinical performance studies. Our team specialises in:
- Design and conduct of both interventional and non-interventional clinical performance studies across Europe
- Project management
- Essential documents development
- Application package preparation and regulatory applications to Ethics Committee and National Competent Authorities
- Selection and qualification of sites, and contact with key opinion leaders
- Design of Case Report Forms and Electronic Data Capture platforms programming
- Clinical Performance Studies monitoring and site management
- Data management
- Biostatistics, including sample size calculation
- Medical writing: Data Management Plan, Statistical Analysis Plan and Clinical study report
Subject Matter Experts
Ruben Ruiz, M.Sc.
Clinical Affairs Manager
Lucía García, M.Sc. Associate Manager Clinical Studies & IVD team lead