For Combination Products, the intended use and mode of action is the deciding criterion whether the study is regulated by the MDD (93/42/EEC; 2007/47/EC)/AIMDD (90/385/EEC; 2007/47/EC) or the MPD (2001/83/EC; EU No 536/2014).
The MEDDEV Guidelines give more advice and information about requirements during the life cycle of a Medical Device to harmonize the processes within the EU. Section 2.1 of MEDDEV contains guidance on the scope, field of application, definition. In the MEDDEV 2. 1/3 rev 3, further information for borderline products, drug-delivery products and medical devices incorporating, as an integral part, an ancillary medicinal substance or an ancillary human blood derivative with significant examples are documented.
Although a unique process could be assumed due to existing EU Directives (MDD 93/42/EEC, AIMDD 90/385/EEC, MP 2001/83/EC), the implementation into national law in each EU Member State creates differences between the EU countries. Performing Clinical Studies, information on the national law of the participating Member States needs to be collected, and the most stringent applies for all.
SAE reporting is always a very critical part of a Clinical Trial, and within the EU, differences between requirements by national Law between the EU Member States also appear.
For example the German MPSV (Medical Device Safety Plan Ordinance) does not cover “fetal distress, fetal death or a congenital abnormality or birth defect” as seriousness criterion in the SAE definition, while the Austrian MPG includes “the occurrence of a malignant tumour” to be “considered serious in any case”, both differ from the definitions given by the ISO 14155:2011 and the Directives.
As these challenges occur within Europe, where Medical Device Clinical Trials are conducted under GCP as given by ISO 14155:2011, what would it be like in International Medical Device Clinical Trials, as the ISO 14155:2011 is not globally accepted as GCP, and some Countries follow the GCP given by ICH E6? What does the SAE reporting section of the protocol need to content?
The ICH E6 4.11.1 states: All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that the protocol or other document identifies as not needing immediate reporting
The ISO 14155:2011 8.2.5 states: The sponsor […] shall […] c: report or ensure the reporting, to the EC by the principal investigator(s), of all serious adverse events and device deficiencies that could have led to a serious adverse device effect (incident), if required by national regulations or the CIP or by the EC
This means: to be aware of international and local requirements, ISO standards, and MEDDEV Guidelines, as well as the ICH Guidances is critical not only at the time of reporting or conducting – it starts much earlier: at study planning / Protocol writing / statistical considerations; not only for safety reasons, but also for economic reasons.
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