The ISO 14155 standards were created to clarify the design, conduct, recording and reporting of clinical investigations carried out in human subjects to assess the safety or performance of medical devices for regulatory purposes. ISO 14155 is in its second edition: ISO 14155:2011. While ISO 14155 is not law in the United States, it plays a role similar to ICH Good Clinical Practices Guidelines (E6) and has been officially recognized as a standard by the FDA since 16 March 2012.
In United States, medical device clinical trials must comply with FDA Code of Federal Regulation (CFR), in particular 21 CFR Parts 11 (Electronic Records), 50 (Informed Consent), 54 (Financial Disclosure), 56 (IRBs), and 812 (IDEs). Investigational device exemption (IDE) trials are required for some Class II and all Class III investigational devices intended for marketing in the U.S.
The 21 CFR 812.100 requires that the sponsor ensures that the investigation is conducted according to the FDA regulations, as well as the investigator agreement, the investigational plan, and written requirements of the Institutional Review Board (IRB) under which the investigation is being conducted.
If any of these regulatory documents specify that the study should be conducted according to ISO 14155 standard, the investigator must also comply with these guidelines. Even if ISO 14155 is not required, such in the case of post market studies, it is still good practice to conduct medical device trials to this higher standard because doing so affords greater participant protection and data integrity. In addition, some national regulations require compliance with ISO 14155, regardless the regulatory status of the product so it is wise to consult the specific regulatory body.
FDA regulations and ISO 14155 standards include many overlaps, but also some unique aspects. To comply with both, it is important to understand these differences. The following tables and discussions compare FDA regulations and ISO 14155 in the five areas where FDA investigators most often find noncompliance with FDA regulations.
- Failure to follow the investigational plan and/or regulations
- Deviations from the protocol
- Inadequate recordkeeping
- Inadequate accountability for the investigational product
- Inadequate subject protection – failure to report AEs and informed consent issues
Other similarities and differences between the FDA regulations and ISO 14155 that do not pertain to these five areas are not included in this overview.
Differences are marked in red in our white paper here.
Whether conducting a US-based study with additional sites OUS or conducting an entire study outside the US, sponsors must stay well-informed about the multiple national and international requirements set to ensure a well-controlled trial that will withstand the scrutiny of worldwide regulatory agencies. While conducting a trial under the umbrella of both 21 CFR and ISO 14155:2011 (ISO 14155) will position the sponsor well globally at trial end, implementing these dual standards can also create confusion during study conduct.
In this paper we focused on the key differences between 21 CFR and ISO 14155 related to common findings observed during inspections that could be beneficial for sponsors and study teams.
The FDA seeks to protect public health and human subject well-being through cautious oversight of all US clinical device trials, and similarly the ISO 14155 was created to provide a worldwide guidance to the design, conduct, recording, and reporting of clinical investigations carried out in human subjects that assess the safety or performance of medical devices for regulatory purposes.
Conducting an investigation according to both principles should result in the highest integrity device trial that affords the most stringent level of protection for human research subjects. While this may be challenging, it can be accomplished with proper preparation. Ensuring trials comply with both sets of standards allows companies that conduct international trials to feel confident that the resulting data is acceptable not only in the US, but also to worldwide regulatory agencies. Please take time to consult our website (www.akrnconsulting.com) and let us know if you need our help to plan your clinical trials.
AKRN Scientific Consulting, S.L. is a privately-owned life science consulting firm based in Madrid, Spain. We are committed to partner with Medical Device companies developing innovative technologies improving health care for more people and to offer customized solutions crafted to each client’s needs. We combine therapeutic expertise and decades of industry know-how with and excellent service and responsiveness to provide our customers with tailor-made solutions that can stand up to rigorous scientific and regulatory evaluations.