Reporting of serious adverse events (SAEs) and device deficiencies (DDs) for performance studies

SAE and DD reporting obligations according to IVDR and MPDG

Since the IVDR came applicable on 26.05.2022, the reporting of serious adverse events (SAEs) and device deficiencies (DDs) must be carried out in accordance with the European Regulation 2017/746 (IVDR) in conjunction with the Medical Devices Law Implementation Act (“Medizinprodukterecht-Durchführungsgesetz”, MPDG) for all clinical investigations that must be applied for or notified to the federal higher authority.

Note: This does not apply to performance evaluation studies that were initiated under the legal framework of the MPG and are considered to have been begun at the date of application of the IVDR on 26.05.2022 within the meaning of Section 100 (3) MPDG. For these performance evaluation studies, the legal framework of the MPG and its associated ordinances, including the Medical Devices Safety Plan Ordinance (“Medizinprodukte-Sicherheitsplanverordnung”, MPSV), continues to apply.

Which reporting forms are to be used for serious adverse events (SAE) and device deficiencies (DD) from 26.05.2022?

Until reporting via the central European database EUDAMED or the German Medical Devices Information System (DMIDS) is possible, the following requirements apply:

From the date of application of the IVDR on 26.05.2022, the MDCG-SAE reporting table (see appendix of the MDCG guideline "Guidance on safety reporting in clinical investigations") should be used as a replacement for the MEDDEV-SAE reporting table.

For SAEs or device deficiencies (DD) from German trial sites, the SAE / DD individual notification form of the BfArM must still be used.

In addition, the BfArM continues to expect the quarterly summary SAE / DD assessment. (Further details can be found in the overview table on reporting obligations in Germany).
All SAE / DD reports are to be sent to the functional mailbox mpsae@bfarm.de .

What are the reporting deadlines for serious adverse events (SAE) and device deficiencies (DD) from the date of application of the IVDR?

The reporting deadlines are based on the requirements of the MDCG guideline "Guidance on safety reporting in clinical investigations":

• For all reportable events according to Article 76 IVDR which indicate an imminent risk of death, serious injury, or serious illness and that requires prompt remedial action for other patients/subjects, users or other persons or a new finding to it:
  Immediately, but not later than 2 calendar days after awareness by sponsor of a new reportable event or of new information in relation with an already reported event.
  This includes events that are of significant and unexpected nature such that they become alarming as a potential public health hazard. It also includes the possibility of multiple deaths occurring at short intervals.
  These concerns may be identified by either the NCA or the manufacturer.
  
• Any other reportable events as described Article 76 MDR or a new finding/update to it:
  Immediately, but not later than 7 calendar days following the date of awareness by the sponsor of the new reportable event or of new information in relation with an already reported event.

Condition for reporting to BfArM	Country in which the SAE / DD occurred	Timeline for reporting to BfArM	Form
a) SAE for which a causal relationship with the device, the comparator or the study procedure is reasonably possible; b) device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate; c) any new knowledge relating to an event referred to in points (a) and (b)	Germany	immediately	Individual report German SAE Report Form PDF, 983KB, File does not meet accessibility standards Please send to mpsae@bfarm.de
	all other countries where the performance study is performed	immediately	Summary table MDCG SAE Report Table Please document all SAE cumulatively in the same Excel spreadsheet. Please send to mpsae@bfarm.de
all reportable SAEs / DDs* and in addition SAEs / DDs* that are included in Endpoints according to the CIP *In the case of clinical investigations according to Art. 70 (1) IVDR incidents instead of DDs have to be reported.	all	quarterly	Summary evaluation of SAEs / DDs or incidents Evaluation DOCX, 25KB, File does not meet accessibility standards Annex 3.1 complication rates XLSX, 43KB, File does not meet accessibility standards Please send to mpsae@bfarm.de Please observe our Notes PDF, 485KB, File does not meet accessibility standards

Please note: In the case of performance evaluation studies (performance studies) which are deemed to have commenced on 25.06.2022 in accordance with Section 100(3) of the MPDG, the SAE reporting obligations continue to be based on the requirements of the Medical Devices Safety Plan Ordinance (“Medizinprodukte-Sicherheitsplanverordnung”, MPSV).

What changes with regard to the SAE/DD reporting obligations in comparison of the IVDR to the MPG / MPSV?

Definitions
When the IVDR comes applicable, its definitions of a serious adverse event and a device deficiency apply and replace the definition from the MPSV that was valid in Germany until then. The following definitions are effective as of 26.05.2022:

Article 2, point (60):
‘adverse event’ means any untoward medical occurrence, inappropriate patient management decision, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a performance study, whether or not related to the device for performance study;

Article 2, point (58):
‘serious adverse event’ means any adverse event that led to any of the following:

a) a patient management decision resulting in death or an imminent life-threatening situation for the individual being tested, or in the death of the individual's offspring,
b) death,
c) serious deterioration in the health of the individual being tested or the recipient of tested donations or materials, that resulted in any of the following:

i) life-threatening illness or injury,
ii) permanent impairment of a body structure or a body function,
iii) hospitalisation or prolongation of patient hospitalisation,
iv) medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function,
v) chronic disease,

d) foetal distress, foetal death or a congenital physical or mental impairment or birth defect;

Article 2, point (59):
‘device deficiency’ means any inadequacy in the identity, quality, durability, reliability, safety or performance of a device for performance study, including malfunction, use errors or inadequacy in information supplied by the manufacturer;

Which reporting obligations apply to which performance study?

Performance study pursuant to Article 66(7) IVDR:
- SAE / DD reporting obligations according to Article 76 IVDR

PMPF study according to Article 70(1) IVDR (with additional invasive and/or burdensome procedures):
- Provisions on vigilance laid down in Articles 82 to 85 IVDR and in the implementing acts adopted pursuant to Article 86 IVDR.
- SAEs, where a causal relationship between the serious adverse event and the preceding performance study has been established (Article 76(5) and (6) IVDR).

PMPF study without additional invasive and/or burdensome procedures:
- Provisions on vigilance laid down in Articles 82 to 85 IVDR and in the implementing acts adopted pursuant to Article 86 IVDR apply.
(SAEs / DDs do not have to be reported to the federal higher authority.)

Performance evaluation study (performance study) which is/was considered to have started on 26.05.2022 within the meaning of Section 100 (3) MPDG:
- For these performance evaluation studies, the MPG with its annexed ordinances, in particular the Medical Devices Safety Plan Ordinance (“Medizinprodukte-Sicherheitsplanverordnung”, MPSV), continue to represent the binding legal framework for the SAE reporting obligations even after the date of application of the IVDR (Section 5(4)-(7) MPSV).

This also includes the definition of a serious adverse event, which differs from those of the IVDR and the MDR (see § 2 No. 5 MPSV).

Important notes on the SAE / DD summary assessment

The assessment can be sent at the same time as an SAE / DD reporting table (MDCG - Clinical Investigation Summary Safety Reporting Form) and should be updated regularly at 3-month intervals. For further information, please refer to the associated information sheet.

BfArM expects significant comparative data from scientific literature or other sources for all serious complications that may be related to the use of an investigational medical device, including adverse events associated with the medical procedures involved, to be included in the quarterly summary evaluation of serious adverse events. In addition to literature data, data derived from the risk analysis or comparable sources may be used. Such comparative data is to be provided in the Excel spreadsheet “complication rates” or, where needed, in other chapters of the summary evaluation report.

The BfArM generally requires that all SAEs be carefully evaluated, regardless of whether or not they are related to the investigational medical device or anticipated. Likewise, not only safety endpoint events but all SAEs have to be assessed with regard to patient safety and are to be compared to acceptable occurrence rates.

The sponsor must indicate the criteria that are applied for benefit-risk evaluation during the course of the performance study.

Patient safety must be evaluated with regard to the entire medical procedure that is involved in the use of the device. This includes access complications as well as preexisting medical conditions (possible contraindications), complications when using the investigational device in combination with other devices and any other factors that may increase the risk for patients.

A benefit-risk evaluation in a performance study means comprehensive evaluation of all events with relevance for the safe use of the medical device, irrespective of the relation to the investigational device, the medical procedure involved or any other factor and regardless of whether they are anticipated or not.

Important notes on completing the MDCG SAE / DD reporting table

The MDCG table is to be completed consecutively. Please always fill in the complete information for each case. New findings / updates to already reported events with relevance for the assessment may be added at any time. Please indicate your entry as "modified" in such cases.

In the columns for dates, please only enter pure dates in the "dd/mm/yyyy" format according to the MDCG specifications. Please avoid empty cells in cases where such information is available (e. g. in the column "Description of Event").

However, please do not make any formal changes such as:

• correcting spelling errors including punctuation
• adding and removing spaces and line breaks
• format changes

Such changes create duplicates in our SAE assessment process. Please note that such duplication of data may cause additional fees.

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German individual SAE Report