Vigilance of In Vitro Diagnostics (IVD)
Competent Higher Federal Authority for the Safety of In Vitro Diagnostic Devices (IVD)
The Paul-Ehrlich-Institut has been the competent higher federal authority for the centralised collection and assessment of serious risks of certain IVDs since 1 January 2002.
Beginning on 26 May 2022, the Paul-Ehrlich-Institut will extend its competence to all class D products (life-threatening infections, pathogens transmissible through blood and tissue) and part of the class C tests (sexually transmitted infections, examination for genetic disorders in the embryo or foetus).
The definitions of the IVD classifications can be found in Annex VIII of the EU Regulation for in vitro diagnostic medical devices (IVDR 2017/746).
The function of the competent authority is carried out by the "Pharmacovigilance II" unit of the Paul-Ehrlich-Institut.
The duties of the Paul-Ehrlich-Institut in the field of medical devices are laid out in the Medical Device Law Implementing Act (Medizinproduktedurchführungsgesetz, MPDG) and the Medical Devices User Reporting and Notification Ordinance (Medizinprodukte- Anwendermelde- und Informationsverordnung, MPAMIV).
The Institute's primary duty consists of evaluating incident reports. These are reports of events that involve medical devices already on the market and in which a product defect is considered to be the cause of a death or a serious decline in the health of an individual, such as a person who has undergone a test.
The Paul-Ehrlich-Institut receives these reports from users (e.g. blood donation services, diagnostic laboratories) or the manufacturers of in vitro diagnostic medical devices (IVD). The Paul-Ehrlich-Institut subsequently carries out a risk assessment of the incident and assesses the usefulness of corrective or preventive measures taken by the IVD manufacturer. In the case of national IVD manufacturers, the Paul-Ehrlich-Institut may propose further corrective measures, as the Institute is responsible for the monitoring of the competent Federal state authorities. The state authorities are empowered to mandate these recommendations if necessary and to monitor their implementation. In the case of incident reports requiring corrective action in several EU Member States, the Paul-Ehrlich-Institut assumes a coordinating role in order to ensure a uniform approach throughout Europe.
In the case of class D products, the competent authorities should be informed of certificates issued by the notified bodies and have the right to check the assessment carried out by the notified bodies.
Pursuant to section 31 of the MPDG or Annex XIV of Regulation (EU) 2017/746, the Paul-Ehrlich-Institut is responsible as the competent higher federal authority for the approval of performance evaluation tests of IVD in Germany or of interventional clinical performance studies. Such performance evaluation tests, which are examined in parallel by an ethics committee, are the basis for the granting of CE certification for an IVD. An application must be submitted to the competent higher federal authority (via the IT portal of the German Medical Devices Information and Database System, DMIDS) to initiate the approval procedure for performance evaluation tests of IVDs.
The Paul-Ehrlich-Institut also makes decisions on the classification of individual IVDs and their distinction from other products at the request of a competent state authority, a notified body or an IVD manufacturer.
IVDs under the responsibility of the Paul-Ehrlich-Institut
The Paul-Ehrlich-Institut is responsible for the assessment of the technical and medical requirements and the safety of class D IVDs and selected class C IVDs, in accordance with section 39 of the MPDG.
Rules for the corresponding classification of IVDs can be found in EU Regulation 2017/746. The responsibility of the Paul-Ehrlich-Institut is limited to products that comply with the following rules.
Class D products intended for the following purposes:
- detection of the presence of, or exposure to, a transmissible agent in blood, blood components, cells, tissues or organs, or in any of their derivatives, in order to assess their suitability for transfusion, transplantation or cell administration (rule 1);
- detection of the presence of, or exposure to, a transmissible agent that causes a life-threatening disease with a high or suspected high risk of propagation (rule 1);
- determining the infectious load of a life-threatening disease where monitoring is critical in the process of patient management (rule 1).
- Devices intended to be used for blood grouping or tissue typing to ensure the immunological compatibility of blood, blood components, cells, tissues or organs that are intended for transfusion or transplantation or cell administration (rule 2).
Class C products intended for the following purposes (rule 3):
- for detecting the presence of, or exposure to, a sexually transmitted agent;
- for detecting the presence in cerebrospinal fluid or blood of an infectious agent without a high or suspected high risk of propagation;
- for screening for congenital disorders in the embryo or foetus;
- for screening for congenital disorders in new-borns babies where failure to detect and treat such disorders could lead to life-threatening situations or severe disabilities.
In contrast, the Federal Institute for Drugs and Medical Devices (BfArM) is responsible for all other IVDs in the EU Regulation as well as for IVD devices and the required software of the parameters listed in the above listings.
Reporting obligations and reporting deadlines
Reporting obligations according to chapter 5 of the MPDG and section 3 of the MPAMIV
- The person responsible must report incidents that have occurred in Germany, as well as recalls carried out in Germany, to the competent higher federal authority. They shall report any incidents and recalls that have occurred in other contracting states to the Agreement on the European Economic Area to the competent authorities there. Recalls that are also carried out in the European Economic Area due to incidents that have occurred outside the European Economic Area must be reported. The notification of such corrective measures, including the underlying incident, must be made to the competent higher federal authority if the person responsible is based in Germany.
- Anyone who operates or uses medical devices professionally or commercially must report any incidents to the competent higher federal authority. This applies mutatis mutandis to doctors and dentists who become aware of incidents as part of the diagnosis or treatment of patients treated with medical devices.
- Anyone who, without having designated a person responsible for such duties, professionally or commercially or in fulfilment of legal duties or obligations, dispenses medical devices to the end user for personal use by patients or other laypersons, must report any incidents to the competent higher federal authority. In all other cases, distributors and retailers shall inform the person responsible of any incidents communicated to them.
- The obligations under paragraphs 2 and 3 shall be deemed to have been fulfilled for medical professionals insofar as reports are made to commissions or other institutions of the medical professions, which, within the scope of their duties, cover medical device risks, and an immediate forwarding to the competent higher federal authority is ensured there.
- Serious adverse events must be reported by the sponsor and the investigator or principal investigator to the competent higher federal authority. If the clinical trial is also carried out in other contracting states to the Agreement on the European Economic Area, the sponsor must also report to the competent authorities there. If a clinical trial or a performance evaluation test is also carried out in Germany, the sponsor must also report serious adverse events to the competent higher federal authority outside of Germany.
- The competent higher federal authority confirms receipt of the report to the reporting person or body. The authority shall immediately inform the person responsible of any reports with all necessary information or a justification as to why no incident has occurred. If the competent higher federal authority does not agree with this justification, it may request a notification in accordance with paragraph 1.
- The person responsible must report incidents in accordance with the urgency of the risk assessment to be carried out, but at the latest within 30 days of becoming aware of it. The report must be made immediately in the event of imminent danger. Recalls and incidents within the meaning of section 3 (see above) must be reported from the start of the implementation of the measures at the latest.
- Reports and notifications pursuant to section 3 paragraphs 2 to 5 (see above) must be made immediately.
The higher the assessment of the risk potential arising from the incident, the lower the reporting agent should interpret the reporting threshold. The competent unit "Pharmacovigilance II" of the Paul-Ehrlich-Institut should be contacted in advance if there are any questions.
Definitions of important terms in the field of IVD vigilance
Definitions according to the Medical Devices User Reporting and Notification Ordinance (MPAMIV)
"Incident" is defined as a malfunction, failure or alteration of the characteristics or performance or incorrect labelling or instructions for use of a medical device that has, or may have, directly or indirectly resulted in the death or serious deterioration of the health of a patient, user or other person.
An action taken to eliminate, reduce or prevent the recurrence of a risk posed by a medical device.
A corrective measure that causes the return, replacement, conversion or retrofitting, the rejection or destruction of a medical device or gives instructions to users, operators or patients for the further safe use or operation of medical devices.
Recommendation for action
A notice from the person responsible initiating a corrective action.
Serious adverse event (SAE)
A serious adverse event is any adverse event occurring in a licensed clinical trial or a licensed performance review that has, or may have, directly or indirectly resulted in the death or serious deterioration of the health of a subject, user or other person without regard to whether the event was caused by the medical device; the foregoing applies mutatis mutandis to serious adverse events that occurred in a clinical trial or performance review that was granted an exemption from the licensing requirement.