On 28 July 2020, the International Organization for Standardization (ISO) published an updated version of their widely used international reference for good clinical practice (GCP) for medical device investigations, ISO 14155:2020, Clinical investigation of medical devices for human subjects – Good clinical practice. This revised standard is valid from the time of publication with no transition period. It cancels and replaces the previous version from 2011. In this article, I’ll discuss the main updates.
What is ISO 14155?
The ISO 14155 standard provides GCP for clinical investigations of medical devices including specific requirements for the “design, conduct, recording and reporting.” It is published by the International Organization for Standardization (ISO) and applies to both pre and post market investigations.
This standard is used for regulatory compliance in Europe (the EU Medical Device Regulation (MDR) 2017/745 references the 2011 standard) and globally. The U.S. Food and Drug Administration (FDA) recognizes ISO 14155 and accepts clinical data collected outside the U.S. when the standard is followed for medical device investigations.
ISO 14155 is very similar to the International Council for Harmonisation (ICH) E6(R2) guideline and aims to:
- Protect subjects
- Ensure data integrity
- Define sponsor, investigator, and IRB responsibilities
- Be the standard that allows acceptance of clinical data by regulators
ISO 14155 differs from ICH E6 and FDA regulations in some areas. A footnote in the ISO standard advises that when there are differences in the requirements, “the most stringent apply.”
Why was ISO 14155 updated?
This standard was updated to harmonize with other global GCP guidelines and best practices. Also, the revisions reflect a modernization of research practices, including adopting flexibilities for new technologies (such as electronic consent and signatures), embracing new approaches such as quality by design and risk-based monitoring, and considering issues such as data privacy.
Is ISO 14155:2020 the same as ICH E6(R2)?
Similar to the ICH E6(R2) guideline that provides GCPs for clinical trials of drugs and biologics, the ISO 14155 standard aims to provide a standard for acceptance of clinical trial data in different countries. The ISO standard differs from ICH in that it is specific for investigations of medical devices.
Main Revisions
The main updates are listed below:
- Addition of GCP Principles. The revised standard includes a summary of 13 GCP principles, that aligns ISO with ICH E6(R2).
- Transparency. Consistent with many regulations, the standard requires registration of the investigation to a publicly accessible database prior to recruitment of the first subject. It also added that results of the investigation should be posted on “completion,” which means when follow-up is complete, unless there is another specified timepoint in the CIP. A footnote includes that national regulations can apply regarding the timing of registration and updating the registry.
- Addition and Updates to Annexes. ISO 14155 revisions include additional informative and normative annexes (note about terminology: “informative” annexes are best practice and equivalent to “should,” whereas “normative” annexes are equivalent to regulatory “must”).
– These work to harmonize the standard with ICH E6(R2) and regulations.
– For example, the standard now includes Annex H Application of ISO 14971 to clinical investigations as informative. ISO 14971 “provides a general framework to systematically manage risks associated with medical devices.” By including this Annex H, the ISO 14155 standard now has requirements for risk assessment, risk management, and risk mitigation.
- Quality by Design. The standard took a large stab at including key quality by design principles and practices into the revisions. These include inclusion of clinical quality management, inclusion of risk-based monitoring, and reinforcement of risk management from clinical investigation planning to results sharing.
Additional Revisions
There were additional minor revisions as well to terminology, essential documents, and consent.
- New and Altered Terminology. There were minor revisions to some terms and to their footnotes (which are not listed below), and the numbering was revised. Some of the revisions are meant to harmonize terminology with other GCP guidance documents and best practices, and some are meant to provide clarity and specificity. The table below lists the new terms and the terms with altered definitions.
| New Terms | Altered Definitions |
| – Audit trail
– Certified copy – Computer system – Control group – Effectiveness – Electronic record – Quality assurance (QA) and quality control (QC) – Serious health threat – Validation – Verification
|
– Device deficiency
– Endpoints – Hypothesis – Investigational Medical Device – Informed consent – Legally designated representative – Medical device – Point of enrollment – Serious adverse event – Source document – Use error – Vulnerable subject |
- Electronic consent. The revisions include a footnote that “dated signatures can be electronic” meaning that subjects can sign consent electronically.
- Informed consent. The standard had minor but important revisions to consent.
– Consistent with updates to the Common Rule (45 CFR 46, Subpart A), the consent revisions include emphasis on subject understanding and rights (such as the right to withdraw and receive new information).
– The term “legally authorized representative” was updated to “legally designated representative” but the meaning is generally still the same.
– For subjects unable to read or write and providing their consent orally, the updated standard includes that an “independent and impartial” witness should be present (adding the word “impartial” to align with ICH E6).
– A new item was added under “Confidentiality” that requires a statement in the consent that the subject agrees to have their personal data transported outside of the geographic region (as applicable based on other national requirements). This is a nod towards the European Union’s General Data Protection Regulation (GDPR) that has specific rules about data transfer.
– Further consent additions include disclosure about plans to contact the subject for follow-up and disclosure that the study will be registered in a publicly accessible database.
– Minor revisions also included that the subject signature form includes that the subject had sufficient time to consider participation and that no loss of benefits for refusal to participate or withdrawing from the research.
Are CITI Program modules updated to the new standard?
CITI Program modules are current with the ISO 14155:2020 standard. We had expert review and revision for following CITI Program courses:
Learners who complete CITI Program modules after 15 December 2020 will receive the updated content automatically.
