Reference member state

National Competent Authorities are primarily responsible for managing responses to pharmacovigilance issues on their territory. However, the reference Member State is... 

Identical applications are submitted to those member states where marketing authorizations are sought. The first member state that reviews the application is called the Reference Member State. It notifies other states, called Concerned Member States. Concerned Member States may suspend their own evaluations to await assessment by the Reference Member State. The decision of the Reference Member State is forwarded to the Concerned Member States. If the Concerned Member States reject mutual recognition, the matter is referred to the CHMP of the EMEA for arbitration. The EMEA forwards its opinion to the European Commission, which makes the final deci-... 

This is the name of what we used to know simply as the data sheet, or colloquially as the package insert. The SPC is the document that must be submitted in draft by companies to the MHRA/Reference Member State/European Medicines Evaluation Agency upon application for a marketing authorisation and, once approved, must then be provided to prescribers or suppliers of medicines, either with the product or at the time of promotion or within the previous 15 months of promotion of the product, written or verbal. The SPC includes the prescribing information for the product and represents the product licence approval for the medicine (see Section 12.2.1.1). It is the definitive statement between the competent authority and the company and, more importantly, is becoming the common basis of communication between the... 

This guideline lays down the roles and responsibilities of the MAH and of the national competent authorities in respect of the products authorised through the national procedures (including the mutual recognition procedure). Also defined are the roles and responsibilities of the Reference Member States (for mutual recognition products) and of the rapporteur and EMEA for centrally approved products. The role and responsibilities of the MAH include having a named, qualified person responsible for pharmacovigilance at the EU level, and there may be a need for an additional named person at the national level when this is required. 

Decentralized Procedure (DCP) The decentralized procedure was established as an application route in late 2005. This procedure is essentially a combination of the national and the mutual recognition procedures. The applicant chooses a reference member state to undertake the initial assessment. On completion of the RMS assessment, the concerned member states can put forward additional questions to those raised by the reference member state. If the questions are answered by the applicant to the satisfaction of the reference member state and concerned member states, the drug can be authorized. The benefit of the decentralized procedure is that all concerned member states are provided with the application dossier from the start of the procedure. 

The Decentralized Procedure is made on the basis of mutual recognition. Council Directive 93/39/EEC has been implemented in all member states in accordance with Directives 65/65/EEC and 75/319/ EEC. The sponsor makes a submission to the national health authority of one member state, with a request to assess the dossier for mutual recognition. Within 210 days, the so-called Reference Member State (RMS) must approve the application, prepare an assessment report, and agree on an SPC. The clock may be stopped to obtain further information during this time. 

In January 1995, Directive 75/319 of the Council of the European Communities came into force. The regulation introduced new procedures whereby a European MA may be obtained. The net effect of this has been to move work from a national to a European basis, particularly for novel chemicals. The IMB is active in both the centralized and decentralized (mutual recognition) licensing processes, having acted in the centralised process as rapporteur or co-rapporteur on 12 occasions, and having been Reference Member State (RMS) in approximately 10 decentralized applications. 

Table 7. Simplified overview of application fees for 1999-2000 (in British pounds). Source Derived from The Medicines (Products for Human Use-Fees) Regulations 1995 SI No. 1116, as amended. RMS = Reference Member State. ... 

Sponsors initially submit their dossiers to a single MS. That MS conducts the initial review, and is termed the reference member state (RMS). When sponsors then request mutual recognition by other MS, the latter are termed concerned member states (CMS). The RMS is selected by the sponsor. 

EU countries, which is designed as the reference member state (RMS). Once the RMS approves the product, it will then send an assessment report to other EU member countries the company desires to market the product. The other EU countries are called the concerned member states (CMSs). They will approve the product if they concur with the assessment of the RMS. The CMS can disagree with the assessment of the RMS based on safety concerns. The company and the dissent- ing CMS will go into arbitration. Oftentimes, the many objections are political in nature, making the MRP a rather protract and chaotic process. Because the company cannot launch the product in any CMSs unless the arbitration is resolved, they will generally withdraw... 

Applicants could choose the country that they would wish to be the initiating or reference country to enter their dossier into the multistate procedure. Some countries were, and still are, more popular than others for use as the Reference Member State by the applicants (see Table 15.2). 

During this procedure, the original national authority and the applicant act jointly. The applicant submits an application and the updated dossier to each Member State where the applicant seeks an approval. The original national authority (now called the Reference Member State, RMS) transmits its original assessment report (updated if necessary) to these Member States (now called the Concerned Member States, CMS), together with the Summary of Product Characteristics (SPC) approved by it. 

When notifying the programmes to which Article 6 refers. Member States shall inform the Commission of the measures they have taken pursuant to paragraph 1. 

Under the current mutual recognition and centralized procedures, variations must be reviewed with, and approved by all concerned member states. The variation is provided under mutual recognition through the reference member state for the original application, and defined timelines exist for review and approval of the variation, based on whether it is a Type I or II submission. The timelines do not include the time required by the application holder to respond to any questions raised by any of the concerned member states. 

---