Pharmacovigilance and Drug Safety

Pharmacovigilance and Drug Safety for the UK and Europe.

EU Regulation for Pharmaceutical Product Registration and Pharmacovigilance Services Input

EU Regulation For Pharmaceutical Product Registration And Pharmacovigilance Services Input

Your pharmacovigilance system could consist of an in-house team or an external expert company providing a pharmacovigilance service – either way, one thing is for sure, you will waste time and money without a very basic understanding of EU rules on product pharmaceutical registration and pharmacovigilance. This article succinctly explains the key concepts of marketing authorisation in the EU via the Centralised Procedure, Mutual Recognition Procedure and Decentralised Procedure. This guide to basic concepts allows you to gain entry level understanding of the three main regulatory pathways before moving on to work with consultants from your pharmacovigilance services.

The Three Vital Routes to Pharmaceutical Product Registration

Any pharmaceutical product which needs a marketing authorisation in order to be sold in one or more EU countries is going to need to follow one of the legal routes in order to be registered:

“Centralised Procedure” – Regulation (EC) No 726/2004

“Mutual Recognition Procedure”

“Decentralised Procedure” – Directive 2001/83/EC.

As well as these three routes, there are some national authorisations which could allow a product to be marketed in the particular member state or states granting them. This can be an avenue to pursue in order to apply for authorisation under the Mutual Recognition Procedure. Wherever the single national marketing authorisation is will become the country which assumes responsibility for monitoring and safety assessment for that particular product.

Key Concepts of The Centralised Procedure

Administration of this legal route to marketing authorisation is the responsibility of the EMEA. A single application is made with the aim of gaining marketing authorisation throughout all the countries of the EU, Iceland, Norway and Liechtenstein. Once products meet the market, the European Commission is then the responsible agency. This Centralised Procedure should be used for new products and those containing novel substances which are designed to treat serious illness. It is also the route for all biotechnology medicines,

One EU countries regulatory authority becomes the official  Rapporteur, and will be responsible for the initial assessments for the Marketing Authority application. A second agency is appointed as the official Co-Raportuer and between the two agencies, the responsibility for safety assessment and monitoring is shared once the product is introduced to the market.

The regulations are stringent and as such, it is essential that the applicants company uses an experienced in house or externally hired pharmacovigilance services company throughout the application process- and of course, after the product has reached the market

Key Concepts of  Mutual Recognition Procedure

When a product has had a marketing authorisation issued by a single EU country but is required to be marketed in other EU countered, the Mutual Recognition Procedure may be the answer. Should an application be successful, in essence, the marketing authorisation is copied by the other countries involved. The nation which issued the marketing authorisation on a national level is known as the ‘Reference Member State’. The other countries the product is applying to be sold in are  known as the ‘Concerned Member States’. After an application has been entered, there will be a 90 day period during which the ‘Concerned Member States’. Enter an assessment phase. If the application is successful, the original marketing authorisation issued by the ‘Reference Member State’ is adopted into identical authorisations by the ‘Concerned Member States’.

If the application is not successful due to objections raised by any of the ‘Concerned Member States’, the matter is subject to referral to the EMEA. There will be a debating process to try to resolve any problems, and should this fail the next step would be binding arbitration. Whilst there are mechanisms in place, there is no substitute for the services of competent pharmacovigilance solutions companies.

Key Concepts of The Decentralised Procedure

This concerns when there is a product for which there has not so far been any marketing authorisation granted in any country in the EU. A dossier will be copied and circulated to all the EU countries in which as marketing authorisation is sought. The company who submit the application are able to decide which country should be the ‘Reference Member State’ under this procedure. The company must prepare a preliminary report within 120 days and circulate it to every ‘Concerned Member State’. If the application is not accepted, it does continue, into a facilitation period. If this remedy is still not successful to resolve the problems, binding arbitration will be imposed.

The Decentralised Procedure again obviously requires expert input at every step of the way from the company’s in house or external pharmacovigilance team.

This summary of the nature of the three legal routes to product registration in the EU should help when deciphering some of the industry jargon surrounding gaining EU product registration. This can assist you in dealing with either an in-house pharmacovigilance department or any external pharmacovigilance services provider.

Product Registration

A marketing authorisation for a medicinal product in more than one Member State in the EU must be sought via one of three procedures: either the “Centralised Procedure”, determined by Regulation (EC) No 726/2004, the “Mutual Recognition Procedure” or the new “Decentralised Procedure”, regulated by Directive 2001/83/EC.

In addition, national authorisations allow for products to be marketed in individual countries in the EU. A product may be authorised in several Member States by a number of national authorisations, or one of these may be used as the basis for a Mutual Recognition Procedure. The regulatory agency of the country concerned has the responsibility for monitoring and assessing the safety of products with national authorization.

Centralised Procedure

This is administered by the EMEA. It consists of one application which, if approved, grants marketing authorisation for all countries within the European Union (and the European Economic Area, i.e. the EU countries plus Iceland, Norway and Liechtenstein).The European Commission is the responsible authority for the products which come to the market through the centralised procedure. The procedure is available to all new, or innovative pharmaceuticals, and is obligatory for biotechnology medicines. It is used for products containing new substances for which the therapeutic indication is the treatment of serious disease.

The regulatory agency of a Member State is appointed as Rapporteur and carries out the initial assessment of the application for Marketing Authorisation; another agency is appointed as Co-Rapporteur. These countries remain responsible for taking the lead in the monitoring and assessment of safety of the product when it is subsequently marketed.

Mutual Recognition Procedure

Here, the marketing authorisation in one Member State, the ‘Reference Member State’, is “mutually recognised” by other ‘Concerned Member States’. There is a 90 day assessment period after which Member States grant a marketing authorisation with an identical summary of product characteristics to that in the Reference Member State, provided that they accept the assessment of the product. If a Member State raises objections and does not recognise the original marketing authorisation the matter may be referred to the EMEA for discussion among the parties: if this fails, binding arbitration is imposed.

Decentralised Procedure

This process can apply where an authorisation does not yet exist in any of the Member States. Identical dossiers are submitted in all Member States where a marketing authorisation is sought. A Reference Member State, selected by the applicant, prepares a preliminary assessment report within 120 days and sends it to the Concerned Member States. They then approve the assessment or the application will continue into a facilitation or, if this fails, a binding arbitration procedure applies.

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