Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Procedures following the Centralised, Mutual Recognition and Decentralised Procedure in case of a negative outcome of the assessment of the marketing authorisation application. Function of the CHMP and the CMD(h) ***

Dr. Karolina Zientek-Lang (Abschlußjahr: 2009)

Language: English

For the authorisation of medicinal products for human use, three procedures are available: Centralised Procedure (CP), Mutual Recognition Procedure (MRP) and Decentralised Procedure (DCP).

The Centralised Procedure, introduced by Regulation (EC) No 726/2004 of 31 March 2004, is accessible for special categories of medicinal products listed in the Annex to this Regulation. Medicinal products which contain a new active substance or constitute a significant therapeutic, scientific or technical innovation, or when the granting of the marketing authorisation via CP is in the interests of patients at Community level, may be centrally authorised upon duly justified applicants request.

The assessment of the marketing authorisation application in the CP is performed by the Committee for Human Medicinal Product (CHMP) and results in an opinion, which can be favourable to the granting of the marketing authorisation, or recommends its refusal. Based on a positive CHMP opinion the European Commission (EC) grants a pan-European marketing authorisation valid for the entire Community market. Correspondingly, refusal of the marketing authorisation by the EC prohibits the placing on the market throughout the Community.
Mutual Recognition and Decentralised Procedures are intended to be used in order to obtain a marketing authorisation in more than one Member State (MS). The Mutual Recognition Procedure (MRP) is applicable only if at the time of application the medicinal product in question has already received a marketing authorisation in at least one of the MS(s). By contrast, the Decentralised Procedure (DCP) can only be used if at the time of application no marketing authorisation for the particular medicinal product exists in any of the MS(s).

The MRP and DCP use the principle of mutual recognition. In both procedures, the concerned Member States (CMS(s)) are requested to recognise, in MRP the marketing authorisation granted by the Reference Member State (RMS), in DCP the assessment of the marketing authorisation application performed by the RMS and its conclusions on it.

A positive completed MRP or DCP is a result of a consensus by the MS(s) concerned on all discussed issues reached by the MS(s) concerned at the end of procedure. Following the MRP/DCP, the marketing authorisation is granted via national procedures in all MS(s) involved.
Analysis of the statistic for CP, MRP and DCP available on the homepage of the EMEA and the Coordination Group (CMD(h)) shows that in the last two years for around 10% (average value for all three procedures) of MAA(s) the outcome of their initial evaluation was negative.
Due to differences between the CP and the MRP/DCP, a negative outcome of procedure has a different form and statement. Therefore, the procedures established to follow a negative completed CP or MRP/DCP have a different aim and implication.

Negative outcome of the CP is a result of a negative CHMP opinion on the MAA dossier given at the end of the 210-days procedure. According to Article 9(2) of Regulation (EC) 726/2004, the applicant has the right to appeal the negative opinion by submitting a request for re-examination within 15 days after the receipt of the CHMP opinion. The Re-examination Procedure is a 60-days procedure where the opinion points identified by the applicant in the request for re-examination are re-evaluated by the CHMP with possible assistance of a Scientific Advisory Group. The Re-examination Procedure is applicable not only to the CHMP opinion given on the MAA(s) submitted for assessment via CP but also to any other CHMP opinion given, e.g., on renewal, annual re-assessment or referral.

Negative outcome of a MRP/DCP is a result of disagreement between MS(s) involved based on the grounds of potential serious risk to public health raised by at least one of the MS(s). According to Article 29(1) of Directive 2001/83/EC, as amended, if the MS(s) fail to reach agreement the points for disagreement are referred in the first step to the Coordination Group (CMD(h)). The second step in the re-evaluation process is the referral to the CHMP, which is according to Article 29(4) of said Directive initiated when during the CMD(h) referral consensus between MS(s) could not be reached. The CHMP opinion given on referrals can be appealed by the applicant via the Re-examination Procedure described above.

In this master thesis the legal basis, procedural rules and timetable for the Re-examination Procedure, CMD(h) referral and CHMP referral, and the function of the CMD(h) and the CHMP are described. Further, based on the statistical data the relevance of all three procedures in the European system for authorisation of human medicinal product is discussed.

Pages: 67,
Annexes: 6 pages