Risk-assessment questionnaire pharmacovigilance
To effectively monitor the compliance of Dutch marketing authorization holders with the Dutch and EU legislation, the Inspectorate has developed a Risk-Assessment Questionnaire Pharmacovigilance. The questionnaire contains questions about the organization in general, but also specific questions about the pharmacovigilance system. It is mandatory for all ‘Dutch’ marketing authorization holders (MAHs) to complete the questionnaire.
Risk score per ‘Dutch’ marketing authorization holder
The information provided to the Inspectorate will be used to calculate a risk score and to determine a MAHs risk. These scores will be ranked and inspections prioritized for the companies with the highest risk scores.
A Dutch marketing authorization holder (MAH) is any organization that holds an authorization which enables it to place a medicinal product on the Dutch market. This includes national, mutual recognition, decentralized and centralized licenses. The country of the location of the organization does not determine whether they are a Dutch MAH. More information is available on the website of the CBG MEB.
The results of the questionnaire 2023
On 2 March 2023, the risk-based questionnaire was sent to the European Qualified Person of Pharmacovigilance (EU-QPPV) of all MAHs with a marketing authorization (MA) of human medicinal products in the Netherlands.
This questionnaire was based on the results from the 2017 and 2020 questionnaire.
The contact details of the EU-QPPV were retrieved from the XEVMPD database. MAHs who have not submitted information on their MA in the XEVMPD database received a letter by post with the request to complete the questionnaire. In addition, they were requested to submit information on their authorized human medicinal products in the XEVMPD database and keep this up to date (article 57(2) Regulation (EC) No 726/2004).
Response
In total, 801 questionnaires were sent. To which 732 MAHs (91%) responded to the request.
Changes of the EU-QPPV
As part of the pharmacovigilance system, all MAHs are required to appoint an EU-QPPV. MAHs were asked to provide the number of different EU-QPPVs that they had between 1 January 2020 and 31 December 2022.
The number of changes of the EU-QPPV
| | in % |
|---|---|
| 1 EU-QPPV or no changes | 61 |
| 2 EU-QPPV's | 28 |
| More than 2 EU-QPPV's | 11 |
Changes to the PV system
Changes to the PV system are a category of interest in the questionnaire because they can be a risk for PV compliance. Examples include MAHs acquiring other MAHs integrating their PV systems, or changes in the safety database.
Changes to the PV system as a result of the acquisition(s)
| x | Pharmacovigilance system | Safety database |
|---|---|---|
| No significant changes | 60 | |
| Organisational and structural changes | 12 | |
| Integration of PV system | 29 | |
| Database migration | 16 | |
| Completely new database | 18 | |
| Not applicable | 66 |
Compliance
In this section, the results regarding compliance of Periodic Safety Update Report (PSUR) submissions, Individual Case Safety Reports (ICSR) and safety variation submissions are shown. The IGJ looks at the percentage of MAHs that have submitted PSURs, ICSRs and variations ‘on time’.
Results are classified into 3 categories of compliance:
- Less than 70% of submissions were on time.
- Between 71 and 99% of submissions were on time.
- More than 99% of submissions were on time.
Compliance with Submission of Safety Reports (PSUR), Individual Case Safety Reports (ICSR) and Variations
| | less than 71 | 71-99 | more than 99 |
|---|---|---|---|
| Safety variations | 7 | 17 | 76 |
| ICSR | 3 | 25 | 73 |
| PSUR | 4 | 12 | 84 |
Outsourcing PV activities
MAHs may outsource PV activities to vendors, distributors or partners. The results below show the different activities that have been outsourced.
PV activities outsourced
| | No | Yes |
|---|---|---|
| EU-QPPV | 56 | 44 |
| National contact person in NL | 30 | 70 |
| Medical information | 51 | 49 |
| Quality complaints | 84 | 16 |
| Global literature | 24 | 76 |
| Local literature | 23 | 77 |
| Case processing | 25 | 75 |
| Electronic reporting | 39 | 61 |
| aRMM | 43 | 57 |
| Signal management | 50 | 50 |
| Variation submission | 74 | 26 |
| Database maintenance | 18 | 82 |
| Risk management system | 51 | 49 |
| Audits | 36 | 64 |
| PSMF maintenance | 62 | 38 |
Audits and inspections
The questionnaire also contains questions regarding audits and inspections of the PV system.
Audits and inspections
| | Yes | No |
|---|---|---|
| Audit in the last 3 years | 94 | 6 |
| Audit of external (distributors, partners) in the last 5 years | 90 | 10 |
Results on a MAH level
The following information will show results of responders on a MAH level instead of PV system level.
The questionnaire was completed on a PV system level, but within the questionnaire, information regarding the MAs within the PV system were asked for each MAH. The total number of MAs in the Netherlands was provided which included centrally authorized products (CAPs) and nationally authorized products (NAPs, including those authorized via the mutual recognition procedure and decentralized procedure). According to the results provided in the questionnaire, 22% of the MAHs have MAs with one or more biological, biosimilar or vaccine products.
Information about the marketing authorizations in the Netherlands
| | Yes | No |
|---|---|---|
| Additional PV activities | 74 | 26 |
| Additional risk minimalization measures | 66 | 34 |
| Additional monitoring (black triangle) | 77 | 23 |
Risk-based inspections
The information collected in the questionnaire in combination with the information retrieved from Eudravigilance and the XEVMPD database will be used to make a risk profile for each MAH. These risk profiles are used as a tool to set up a risk-based national inspection program. The supervisory authority inspections are not within the scope of the risk-based national inspection program and will therefore be conducted as planned according to the inspection program of the EMA.