As a marketing authorisation holder, you are legally obliged to submit reports of adverse reactions to the medicines authorities. There are detailed instructions on what to submit and how this should be done.
ADR obligations based on pharmacovigilance legislation
Individual Case Safety Reports (ICSRs) from the Netherlands must be sent directly to the EMA EudraVigilance database (Organisation Identifier: EVHUMAN).
- Serious ICSRs must be sent within 15 days after the report has become known to you.
- Non-serious ICSRs must be sent within 90 days after the report has come to your attention.
The electronic submission should be delivered to EudraVigilance in an ICH E2B(R2) message or in an ICH E2B(R3) message. Your report is automatically forwarded from EudraVigilance to the relevant national competent authorities.
As a marketing authorisation holder, you must comply with the obligations for recording and reporting reports of suspected adverse reactions (ADRs; Adverse Drug Reactions) as described in the Guideline on good pharmacovigilance practices Module VI – Collection, management and submission of reports of suspected adverse reactions to medicinal products (Rev 2). In addition:
- Dutch reports may be made prepared either in Dutch or in English.
- If submission to EudraVigilance is temporarily impossible due to technical problems, please follow the instructions from the EMA. It is not necessary to inform the MEB separately about this.
Reporting obligations for reporting suspected adverse reactions can be found in Regulation (EC) no. 726/2004 and Directive 2001/83/EC.
The Netherlands Pharmacovigilance Centre Lareb manages the national spontaneous reporting system on behalf of the MEB and forwards the reports to EudraVigilance. As a marketing authorisation holder, you can obtain the Lareb reports (both serious and non-serious) via EudraVigilance in an ICH E2B(R3) message. In order to obtain the correct access rights, you must ensure that your ‘EudraVigilance User Registration’ is in order. Moreover, it is essential that your data in the Art. 57 database are complete and up-to-date. Please consult the EudraVigilance section on the EMA website for more information.
Lareb reports are ‘regulatory reports’; therefore, you do not have to resubmit them to the EudraVigilance database.
Reports from compassionate / named patient use
In the Netherlands, reports of suspected adverse reactions should be actively collected for medicinal products that are used within a compassionate use programme or a Doctor’s Declaration (named patient).
When, as a marketing authorisation holder or applicant for marketing authorisation, an adverse reaction to your medicinal product that is used within a ‘compassionate use programme’ has come to your knowledge, you must follow the guidelines in GVP Module VI. Reports suspected to be related to the medicinal product (as assessed by the primary reporter or by the applicant/authorisation holder) must be sent to EudraVigilance.
For medicinal products that are used based on a Doctor's Declaration, the reporting requirements as published on the website of the Health and Youth Care Inspectorate (IGJ) apply.
Reports from literature
A detailed guidance on the monitoring of the scientific and medical literature has been developed in accordance with Article 27(3) of Regulation (EC) No 726/2004; it is included in GVP module VI, Appendix 2. As a marketing authorisation holder, you must have a strategy for actively monitoring the medical and scientific literature. The MEB and the Health and Youth Care Inspectorate (IGJ) do not have a list available with (local) literature for a search. What you need to monitor differs by type of product, indication(s) for use, and geographical area.
The purpose of literature screening is to detect ICSRs (individual case safety reports) and to identify relevant safety information for a medicinal product. Therefore, the requirement for literature searching does not depend on the marketing status of a product. In line with GVP Module VI, Appendix 2, the literature screening must start at the time of submission of the marketing authorization. Although it is unlikely to find ICSRs when the product is not yet on the market, there may be relevant safety information, for example for similar medicinal products. However, such information is not expected to be published in local journals. The marketing authorization holder is therefore expected to start the global (worldwide) literature screening at the time of submission of a marketing authorization, and the local literature screening when the product becomes available in the country, either via named patient/compassionate use programs, or via regular prescription.
Monitoring by marketing authorisation holder
For active monitoring of reported adverse reactions in the medical literature you can use:
- Standard international literature search databases, such as Medline and Embase
- 'Standard' local medical publications. For the Netherlands, these include Pharmaceutisch Weekblad, Nederlands Tijdschrift voor Geneeskunde, Geneesmiddelenbulletin and Medisch Contact. The local publications must be part of your strategy for a literature search, unless the product is not available in the country (see above).
- Depending on the product (e.g. herbal medicinal product) and/or indication (e.g. cardiovascular), other local publications may also be relevant.
The MEB advises you to record the rationale of your strategy so that it is clear how it was established.
For literature reports you submit to EudraVigilance, you do not have to send the published article as an attachment by default.
Monitoring by the EMA
The EMA is responsible for monitoring a number of substances and selected medical literature to identify potential adverse reactions for medicinal products registered in the EU and for entering the relevant information in the EudraVigilance database. Therefore, as a marketing authorisation holder, you do not have to report suspected adverse reactions to EudraVigilance as they appear in the said medical literature that is monitored by the EMA.
A detailed guideline has been developed to monitor scientific and medical literature. It can be found in GVP module VI, appendix 2.