[ARTICLE] ISO 14155:2020 changes to be aware of when planning, designing or conducting a clinical investigation

The new ISO 14155:2020 – Clinical investigation of medical devices for human subjects – Good Clinical Practice was released in July 2020. This third edition supersedes the 2011 version, which was updated as to conform with the upcoming MDR.
ISO 14155:2020 is expected to be harmonized rapidly without content deviations as it is the European Commission’s priority to provide a reference standard to support the provisions of the MDR pertaining to clinical investigations.
Therefore, the Annex Z showing the correlation between the requirements of the standard and those of the relevant Directives and Regulation should soon be released by the CEN (European Committee for Standardization) for harmonization under the European Directives 90/385/EEC for active implantable medical devices (AIMDD) and 93/42/EEC for medical devices (MDD), and under the European Regulation 2017/745 for medical devices (MDR). No official transitional period has been communicated for this updated standard, and thus it is considered applicable as of its date of publication.

Changes induced by the new ISO 14155:2020

Aside from the main documentary changes listed in the foreword of the standard, the major changes to be aware of when planning, designing or conducting a clinical investigation are:

    • Clinical investigation is now 2.0: ISO 14155:2020 discusses the opportunity for remote monitoring, the acceptability of digital signature for informed consent forms and the validation process for eCRFs systems.


      • Clinical investigations must be registered in a publicly accessible database, such as clinicaltrials.gov. The registration must be updated and results must be published after the completion of the investigation. Previously, certain countries required registration, whereas others did not.


    • It is now an obligation to publish the investigation’s results, whether positive, inconclusive or negative. Previously, the standard only encouraged sponsors to do so.


    • New concept of Serious health threat as a signal that indicates an imminent risk of death and requires immediate actions to be taken by the sponsor and/or the investigator.


    • Clinical investigations, like all other medical devices related processes, should be planned, designed and conducted following a risk-based approach. Whether it is related to monitoring or adverse events reporting, risk management activities should be performed throughout the process of a clinical investigation. The newly added Annex H specifies the ties with ISO 14971.


    • Description of the feedback loop with clinical evaluation and risk management activities, such as the use of the clinical evaluation to justify the clinical development stage, and the clinical investigation design and the update of the benefit-risk analysis.


    • Clinical quality management is reinforced, including CAPA process.


    • The selection of the investigation site should be performed carefully, as it is now specified that facilities should be representative of the intended use environment.


    • In case of device deficiencies, the sponsor is now prompted to recover and analyse the faulty device.


    • Contract Research Organizations (CROs) should be qualified suppliers of the sponsor, according to the sponsor’s QMS.


    • The newly added Annex I brings welcome clarifications on the applicability of the requirements of this standard to the different clinical development stages and includes a useful table for the planning and design of clinical investigation in all phases of the medical device lifecycle.


    • The sponsor must select a local representative if the sponsor is not located in the country of the study. Previously, this was requested by certain local regulations, but not in all countries.


As a medical device manufacturer, we recommend you start your transition today:


  1. Plan and document your transition activities;
  2. Implement ISO 14155:2020 in your QMS and perform a gap analysis to identify any shortcomings with the requirements of the new standard;
  3. Provide internal training on the new standard and affected SOPs (related processes such as risk management, clinical evaluation, CAPA, etc. are particularly relevant to consider);
  4. Review / Update templates for future clinical investigations (Clinical Investigation Plan, Investigator’s Brochure, etc.);
  5. Validate your eCRF system if not already done;
  6. Update contracts with your CRO and make sure they are formally qualified as a supplier.

This article was written by DR Jérôme Randall.
If you are eager to learn more about the changes incurred and gain knowledgeable insights on the application of this standard for clinical investigation planning, design, and conduct, make sure to join our ISO 14155:2020 online training, recognized by Swissethics for Investigator & Sponsor-Investigator Levels
Furthermore, as a Contract Research Organization (CRO), Medidee will assist you with all aspects of your clinical investigation activities, from creating and submitting Clinical Trial Applications to Ethics Committees and Competent Authorities, through to initiating, monitoring and writing Clinical Investigation Reports. Contact us now!