New requirements in the ISO 14155 standard for Medical Device Clinical Investigations
The ISO 14155:2020 (Clinical investigation of medical devices for human subjects – Good Clinical Practice) is the third edition of this standard of reference for the design, conduct, recording, and reporting of medical device clinical studies. It provides guidance to manufacturers and clinical research professionals for how to implement Good Clinical Practice (GCP) for pre and post-market clinical investigations designed to determine safety and performance of a medical device.
The ISO 14155 standard provides the general specifications and requirements for clinical investigations to:
- Protect the rights, safety, and well-being of human subjects;
- Ensure scientific conduct of the clinical investigation and credibility of the clinical investigation results;
- Define the responsibilities of the sponsor and principal investigator;
- Assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of medical devices.
In addition to ISO 14155, clinical investigations in Europe must comply with the Medical Device Directives (MDD) and from 26 May 2021 with the European Medical Device Regulation (MDR). Clinical investigations must further comply with relevant provisions of the EU General Data Protection Regulation (GDPR) 2016/679 the Declaration of Helsinki and applicable national laws.
What is new in the third edition?
The third edition of this standard introduces clarifications to facilitate compliance to other international standards, such as ICH-GCP. The main goal of these changes is to ensure that the standard keeps its global acceptance level. Conducting clinical studies according to GCP is important not only to collect high quality data under ethical conditions, but also to meet regulatory compliance in the European Union (EU) and the United States (US). The US Food and Drug Administration (FDA) recognize the ISO14155 standard for medical device trials and accept clinical data collected outside the US, under the condition that ISO14155-GCP has been followed.
Perhaps the biggest update in ISO 14155:2020 is the strong emphasis on the role of clinical evidence, as presented in the European Medical Device Regulation (MDR), the application of ISO 14971 risk management principles across all stages of clinical investigations, and the improved guidance on clinical study design.
The previous version of ISO 14155 only makes reference to ISO 14971 in terms of “investigational device risks”, and to support risk-benefit assessments to meet clinical investigation design rationale requirements. The new 2020 version adds “clinical risk management” to the list of sponsor responsibilities, which introduces the concept of clinical quality management processes and requires sponsor’s implementation and oversight, even if this task is outsourced to a third-party clinical research organization (CRO).
This new standard is 25 pages longer compared to its previous version (58 vs. 83 pages). It has a total of ten annexes (three additional annexes compared to the second edition); three of which are normative annexes and includes requirements. Some of the major changes are:
- A summary of the GCP principles, aligned with ICH-GCP;
- Reference to registration of the clinical investigation in a publicly accessible database, such as clinicaltrials.gov
- Guidance on risk-based monitoring and considerations when writing the monitoring plan;
- Guidance on statistical considerations, in line with increasing requirements by notified bodies;
- Guidance for Ethics Committees (a new annex);
- Guidance on clinical investigation audits, in line with clinical quality management;
- Reinforcement of risk management according to ISO 14971 throughout the entire process of a clinical investigation;
- Applicability to in-vitro diagnostic medical devices [IVDs];
- Requirements for specific medical expertise in the planning of a clinical investigations.
The new edition also provides clarification on applicability of GCP to different clinical development stages (early feasibility studies, pre-market clinical investigations, post-market studies and registries). This will be valuable when writing the clinical development section of the Clinical Evaluation Plan (CEP) as required by the new European Medical Device Regulation (EU MDR 2017/745).
The standard is valid from the moment of its publication (July 2020) with no official transition period. Although the new ISO 14155 edition includes relevant clarifications and valuable guidance, it should not result in any major changes for sponsor and clinical research professionals already conducting clinical research trials in compliance with the second edition (ISO14155:2011). It will be important to make ensure compliance with the new standard when designing forthcoming MDR clinical strategies and clinical investigations.
How to get the new ISO 14155 standard?
The ISO 14155:2020 standard is not free, but copyright and must be purchased from a ISO member. Purchasing the standard (as PDF and e-Pub layout) will provide the clinical research team valuable tools to ensure appropriate compliance.
In any stage of the clinical development, from early feasibility studies and pre-market clinical investigations, to post-market studies and registries, medical device manufacturers should comply with the ISO14155 standard to ensure ethical and scientific conduct of the investigation, and credibility of the clinical study results.
Conducting a clinical investigation according to the ISO 14155:2020 standard provides a high level of protection for human research subjects and allows companies to perform international device trials that generate clinical data with high integrity that are accepted by regulatory agencies worldwide. Please take time to consult our website and let us know if you need help to plan and execute a ISO 14155 and EU MDR compliant clinical trial.