National Pharmacovigilance Requirements for Marketing Authorisation Holders

Market authorisation holders (MAH) in the EU are legally required to establish and operate a pharmacovigilance system to continually monitor the safety of a medicine throughout its entire lifecycle.

The HPRA operates within the EU pharmacovigilance system, ensuring the safety of medicines across Europe. This page describes national pharmacovigilance requirements and is intended for market authorisation holders (MAHs) and other applicants. It outlines the legal basis for pharmacovigilance activities within the EU and provides guidance on meeting these national requirements.

Pharmacovigilance legislation

The legal basis for pharmacovigilance for medicines for human use in the EU is laid down in Directive 2010/84/EU amending Directive 2001/83/EC, and Regulation (EU) No. 1235/2010 amending Regulation (EC) No. 726/2004.

The legislation is accompanied by Commission Implementing Regulation (EU) No 520/2012, which provides details on operational aspects of the legislation. Requirements for how pharmacovigilance is performed are also outlined in Good Pharmacovigilance Practices (GVP) guidelines.

The revised EU legislation was transposed into Irish law in 2012, by S.I. No. 272 of 2012 (Medicinal Products (Control of Placing on the Market) (Amendment) Regulations 2012), amending the Medicinal Products (Control of Placing on the Market) Regulations 2007 (SI 540/2007).

This information should be read in conjunction with appropriate Good Pharmacovigilance Practices (GVP) guidelines available on the EMA website.

For more detailed information, please refer to the relevant documents via the provided hyperlinks, which will direct you to an external site.

Guide on the preparation and submission of DHPCs

This guide covers the preparation and submission of DHPCs and communication plans to the HPRA for national approval. It applies to DHPCs that are the subject of a regulatory request to promote the safe and effective use of a marketed medicine and to inform healthcare professionals of important new safety information and the need to take certain actions or adapt their practices in relation to a medicinal product.

DHPCs should not include any material that might be considered promotional, commercial or constitutes advertising.

For DHPCs, a specific HPRA identifier should be included at the top of the first page to highlight that it contains important safety information approved by the HPRA and to distinguish the DHPC from other communications received by healthcare professionals. The identifier should be used in full without any modifications. The identifier is available to download in JPG, EPS and PDF formats using the links below.

Guide on the preparation and submission of educational tools and materials

This guide provides MAHs with guidance on preparing, revising, and submitting educational tools and materials to the HPRA for medicinal products specified as a requirement in the risk management plan (RMP).

Only educational materials that are included in an EU-RMP or a condition of the marketing authorisation require HPRA approval.

Please note that submissions must be made at least three months prior to product launch to facilitate assessment of the educational tools and materials and any subsequent revisions.

Additional monitoring requirements and statements to encourage reporting

An inverted black triangle identifies medicinal products under additional monitoring (▼). The primary aim is to enhance reporting of suspected adverse drug reactions for medicines for which the clinical evidence base is less well developed. Additional monitoring status for a medicinal product is always applied in the following cases:

• It contains a new active substance authorised in the EU after 1 January 2011;
• It is a biological medicine, such as a vaccine or a medicine derived from plasma (blood), authorised in the EU after 1 January 2011;
• It has been given conditional approval (where the company that markets the medicine must provide more data about it) or approved under exceptional circumstances (where there are specific reasons why the company cannot provide a comprehensive set of data);
• The company that markets the medicine is required to carry out additional studies, for instance, to provide more data on long-term use of the medicine or a rare side effect seen during clinical trials;
• It is authorised with specific obligations to record suspected adverse drug reactions.

A full description of other situations that may form the basis of a request for a medicine to be included on the list for additional monitoring is further defined in Module X of the guidelines on GVP, in addition to each stakeholder's particular roles and responsibilities, including the MAH.

For medicinal products authorised through national, MRP, or DCP routes that require additional monitoring, the product information should comply with the revised CMD(h) QRD template and country-specific information, as stated in Appendix V. For centrally authorised medicinal products, the MAH should implement the inverted black triangle and additional monitoring statements so that the product information complies with the latest version of the ' 'EMA's annotated QRD template.

MAHs and applicants are also reminded of their obligation to include standard text in the product information, expressly asking healthcare professionals to report suspected adverse reactions following their national spontaneous reporting systems, irrespective of additional monitoring status. The standard text should also be included, asking patients to communicate any suspected adverse reaction to their doctor, pharmacist, healthcare professional, or the national spontaneous reporting system directly.

Submission of non-interventional PASS protocols and reports to the HPRA

If a non-interventional post-authorisation safety study (PASS) is imposed as an obligation by a competent authority and is being conducted on a site or sites within Ireland, the endorsed study protocol, progress reports, and final study report must be submitted to the HPRA in accordance with legislative requirements and GVP-Module VIII Addendum I.

For studies initiated, managed, or financed voluntarily by MAHs (i.e. not imposed as a condition of their marketing authorisation) and conducted on a site or sites within Ireland, only the final study report must be submitted to the HPRA within 12 months of the end of data collection. The submission should be made directly to the Vigilance Assessment Section of the Human Products Monitoring Department at medvigilance@hpra.ie, along with an explanatory cover letter confirming the following details:

• The name of the marketing authorisation holder
• The brand name(s), marketing authorisation number(s) of the products and the active substance (i.e., INN) addressed by the PASS
• Whether the study is an imposed or voluntary non-interventional PASS
• That the study is to be conducted, is being conducted or has been conducted in Ireland
• That the submission concerns either an endorsed study protocol, a progress report or a final study report
• The date of registration and the registration number in the HMA-EMA Catalogue (include a link to study details on the HMA-EMA Catalogue wherever possible), as applicable.