The ISO 14155 standard has undergone some changes in its 2020 edition. This article will present them, and the video below offers an insight into the major changes compared to the previous version of the standard. The video is a part of our online course Introduction to Clinical Investigation for Medical Devices and ISO 14155.
The changes were mainly brought about in order to ensure that the standard continues to keep its global acceptance by regulatory authorities.
Here is a list of the changes:
- Summary of GCP principles (Clause 4)
- Registration of the clinical investigation in a publicly accessible database (Clause 5.4)
- Risk-based monitoring and considerations when writing the monitoring plan (Clause 6.7)
- Clinical quality management (Clause 9.1)
- Statistical considerations (Annex A)
- Guidance for Ethics Committees (Annex G)
- Risk management throughout the entire process of a clinical investigation (Annex H)
- ISO 14155 GCP requirements for different clinical development stages (Annex I)
- Guidance on clinical investigation audits (Annex J)
Clarification on the applicability of GCP
Summary of GCP principles (Clause 4)
First and foremost, the 2020 version of the ISO 14155 standard emphasises the role of clinical evidence as presented in the Medical Device Regulation, the MDR. It also provides clarification on the applicability of GCP to different clinical development stages.
This addition is important for writing the clinical development section of the clinical evaluation plan (CEP) which is required by the Medical Device Regulation. Conducting clinical studies according to GCP is not only essential for the EU, but the US Food and Drug Administration, the FDA, accepts clinical data collected outside the United States provided the ISO 14155 GCP standard was followed.
Other major changes in ISO 14155:2020
Registration of the clinical investigation in a publicly accessible database (Clause 5.4)
This means that the data of the study must be registered in a publicly accessible database such as EUDAMED.
Risk-based monitoring and considerations when writing the monitoring plan (Clause 6.7)
This change means that the extent and nature of monitoring considered appropriate for the clinical investigation can be determined based on the risk assessment and taking into account the study objective, design, complexity, size, critical data points and endpoints, and the degree of deviation from normal clinical practice.
Clinical quality management (Clause 9.1)
Quality management principles shall apply to the processes of the clinical investigation, meaning that it needs to be ensured that the clinical investigation and its data are compliant with the ISO 14155, the clinical investigation plan (CIP), and any subsequent amendment(s).
Statistical considerations (Annex A)
This addition demands that the description of and justification for the statistical design and analysis must be covered and the objectives should serve the purpose of the clinical investigation and shall relate to the hypotheses (if applicable) and endpoints relevant to the target population. Any claims made must be linked to the eligibility criteria for the subject and users.
Guidance for Ethics Committees (Annex G)
The content of Annex G is intended to provide guidance on best practices for the operation of the ethics committees involved in the review of clinical investigations of medical devices.
Risk management throughout the entire process of a clinical investigation (Annex H)
Annex H provides an overview of the application of the risk management ISO standard (ISO 14971) to clinical investigations. The ISO 14971 provides a general framework for systematic management of the risks associated with the use of medical devices.
Perhaps the most important update in the 2020 version is a stronger emphasis on the risk management principles and the application of ISO 14971 principles across all components of clinical investigations. For comparison, the 2011 version only references ISO 14971 in terms of investigational device risks, and in the premarket setting.
The associated risks are estimated (risk analysis) and evaluated (benefit-risk analysis), and the risks are reduced to an acceptable level where necessary (risk control). The effectiveness of risk control is evaluated throughout the product’s lifecycle, which includes the duration of the clinical investigations. A clinical investigation is a method of providing clinical data to allow for conclusions on the acceptability of the benefit-risk ratio.
ISO 14155 GCP requirements for different clinical development stages (Annex I)
Annex I provides a general indication of the possible types of clinical investigations in different clinical development stages.
Guidance on clinical investigation audits (Annex J)
Finally, Annex J provides general guidance on the areas that should be examined during the conduct of clinical investigation audits of sponsor, clinical investigator, and investigation site practices and procedures to determine compliance with this document and, where appropriate, national regulations.
To sum it up, the 2020 version of the ISO 14155 brought several very useful changes to the world of clinical investigations for medical devices. This article and the video offer a brief overview, as the in-depth study of this area is done in our online course. If you found this helpful, make sure you read our other articles.
Would you like to know more about Clinical Investigation?
Take a look at our online Clinical Investigation for Medical Devices and ISO 14155 course that focuses on good clinical practice (GCP) for the design, conduct, recording, and reporting of clinical investigations carried out on human subjects to assess the clinical performance or effectiveness and safety of medical devices.
The course covers an orientation of the clinical investigation process according to the EN ISO 14155:2020 standard and the standard’s relation to MDCG guidance documents. This practical course is suitable for anyone working in clinical research and medical device development, such as regulatory affairs associates, QA engineers, and clinical research specialists.
Maria Nyåkern, Ph.D., is a consultant, entrepreneur, and B2B service provider in the medical device industry; she is the founder of AKRN Scientific Consulting, a CRO specializing in medical devices and minimally invasive cardiovascular therapies.
Maria is also a valued and respected trainer on clinical evaluation and clinical investigations of medical devices according to the EU MDR 2017/745 and the ISO 14155:2020 standard. She has vast ‘ hands-on’ experience, having set up and managed dozens of clinical investigations, and tens of thousands of patients, for different medical devices and indications for many of the top ten medical device manufacturers in the industry.