New requirements and changes in the standard of references for Medical Device Clinical Investigations. The third edition of the standard is under approval for its final publication.
The ISO 14155:2019 (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.
The third edition of this standard emphasizes the role of clinical evidence as presented in the European Medical Device Regulation [MDR] and improves the guidance provided on study design and risk management. It also introduces clarifications to facilitate compliance to other international standards, such as ICH-GCP. The main goal of the changes is to ensure that the standard keeps its global acceptance level. Conducting your clinical studies according to GCP is important not only to collect high quality data under ethical conditions but also for regulatory compliance in the European Union [EU] and US. The US Food and Drug Administration [FDA] accepts clinical data collected outside the US for market applications under the condition that GCP has been followed and FDA recognizes the ISO14155 standard for medical device trials.
The new ISO 14155 version is almost twice as long as its previous version (ISO 14155:2011). Three additional annexes have been included, making a total of 10, out of which three are normative annexes. 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. This will be valuable when writing the clinical development section of the Clinical Evaluation Plan [CEP] as required by the European MDR.
Perhaps the biggest update is the stronger emphasis on risk management principles and the application of ISO 14971 principles across all components of clinical investigations. This is different compared to the current version of ISO 14155 standard which 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 “clinical risk management” is also added to the list of sponsor responsibilities, which both introduces the concept of clinical quality management processes and requires study sponsor´s implementation and oversight, even if, or especially if, this task is outsourced to a third-party clinical research organization [CRO].
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 though to make sure you are up to date with the new standard when you are designing your MDR clinical strategy and setting up upcoming clinical investigations.
The European Medical Device Regulation (EU MDR 2017/745) is put in place to increase the clinical data requirements in support of safety and performance of medical devices. The main propose of its implementation is that it results in a gradual increase in patient safety. The MDR has sparked an increase in clinical investigations in Europe. In any stage of your clinical development, from early feasibility studies and pre-market clinical investigations to post-market studies and registries, the ISO 14155 and GCP can and should be adhered to in order to ensure ethical and scientific conduct of the investigation and credibility of the clinical results.
Maria Nyakern