Pharmacovigilance rules and regulations are understandably complex, aimed at ensuring there is always ongoing good quality reporting and monitoring of pharmaceutical products. There’s no substitute for the professional advice of a pharmacovigilance services company, but this article provides a brief guide to some of the key regulations and guidelines for products marketed in the EU. This guide can be a useful adjunct to professional advice to allow better pharmacovigilance work liaison with related teams in understanding of how the Centralised Procedure, Mutual Recognition Procedure and Decentralised Procedure operate in the EU.
The Three Routes for Pharmaceutical Product Registration
Pharmaceutical products which are to be marketed in one or more member states of the EU must be subjected to one of three procedures to gain the correct Marketing Authorisations status:
“Centralised Procedure” – Regulation (EC) No 726/2004
“Mutual Recognition Procedure”
“Decentralised Procedure” – Directive 2001/83/EC.
There are also certain extra-national authorisations which allow products to be marketed in some single EU member states. This means products may be regulated under separate authorisation in two or more individual EU countries. The Mutual Recognition Procedure allows for application for a national authorisation. The regulatory body in the country in which the original national authorisation was obtained is deemed responsible for product monitoring and safety assessment.
About The Centralised Procedure
This is the administrative responsibility of the EMEA. A single application for marketing authorisation for all the countries in the European Union (and the European Economic Area, meaning all EU countries, Iceland, Norway and Liechtenstein) is made. If applications are approved, at the point they enter the market then all products become the responsibility of The European Commission instead.
This option applies for all new or novel pharmaceutical products and stands as the only route at this time for any biotechnology medicines. It’s also the route for any product which contains novel substances which have the intended purpose of modifying serious disease.
The regulatory agency of one EU country is charged with becoming the Rapporteur, who completes the initial assessments required for a Marketing Authorisation. Their Rapporteur will undertake initial assessments which are necessary for the application for a Marketing Authorisation. In addition, as a double-checking system, there will be the appointment of a Co-Rapporteur, a second agency to oversee things, from a second EU country. Between the two agencies, the safety assessment and monitoring are directed in a controlled manner to allow the product to be introduced onto the market. They will also hold responsibility for the continuing pharmacovigilance work during the time the product will be on sale after its introduction.
Application for a Marketing Authorisation is a key stage to involve a pharmacovigilance services company to ensure the process is properly administrated and staff understand fully what is required at all stages to avoid mistakes.
About The Mutual Recognition Procedure
Here this refers to cases where a marketing authorisation has been authorised by one EU country and it is essentially copied by all other EU countries. There is the ‘Reference Member State’, where the marketing authorisation is granted, and the other countries, referred to as the ‘Concerned Member States’. An application under the Mutual Recognition Procedure incurs a 90 day period during which the ‘Concerned Member States’ accept the product as far as Marketing Authorisations are concerned or raise considerations about the product. If the application is successful, a marketing authorisation is given which is an identical summary of product characteristics to that of the original marketing authorisation in the ‘Reference Member State’.
Sometimes, the process will not automatically succeed. EU countries may raise objections and in the intervening time, the original marketing Authorisation will simply not be recognised by them. The next stage is then referral to the EMEA, where the matters are formally debated, involving all concerned parties. If this step does not resolve the issues, there then will be recourse to binding arbitration.
This is another stage at which professional advice from an experienced relatedpharmacovigilance servicesteam is obviously going to be of paramount importance to guide the applicant throughout the process.
About The Decentralised Procedure
When no marketing authorisation has been issued in any EU country, an identical dossier is submitted to every EU country in which a marketing authorisation is desired. The applying company can nominate which country becomes the ‘Reference Member State’. The company must compile a preliminary report within a timeframe of 120 days and distribute it to appropriate personnel in regulatory agencies of all the EU countries concerned. Those countries are then allowed to approve or raise objections. In the case of objections, there is a facilitation process which is entered into to try to resolve the problems. A further step should facilitation not proved expedient is again, arbitration.
Throughout this regulatory process, the input of the applicant’s pharmacovigilance work team is vital to ensure that the process continues smoothly. The involvement of many countries requires a truly international level of expertise and applicants are advised to partner with experienced pharmacovigilance companies.
Understanding these three basic regulatory pathways can be useful when working with an in-house or external pharmacovigilance services team. From this background reading, it should be easier to begin discussions around the legal requirements of product registration in the EU. In every eventuality, there is no better advice than that of experienced international pharmacovigilance workconsultants.