Legislation and Eligibility
A current framework of legislation that details the centralized procedure is as follows:
- Regulation No 726/2004
Regulation No 726/2004 replaced Regulation No 2309/93 as of 20 April 200. However, only Title IV was implemented at this date. Other Titles were implemented on 20 November 2005 which resulted in some changes to the procedure.
The procedure is COMPULSORY for
- Certain therapeutic classes – new active substances indicated for the treatment of AIDS, cancer, diabetes, and neurodegenerative disorders
- Orphan products
- Veterinary products used for performance enhancement
With effect from 20 May 2008, the procedure was further expanded to become compulsory for
The procedure is OPTIONAL for
- New active substances
- Medicinal products which constitute a significant therapeutic, scientific, or technical innovation or the granting of a Community Authorization for the medicinal products is in the interests of patients at the community level. Immunological veterinary medicinal products for the treatment of animal diseases that are subject to Community prophylactic measures.
A request must be made to the CHMP to seek confirmation of eligibility for products that fall within the optional scope of the procedure.
The procedure is described in the Notice to Applicants, Volume 2A, chapter 4. In summary, it operates as follows.
Assessment Procedure
(a) Pre-submission Phase
Seven months prior to an intended submission the applicant must inform the EMEA of their intention to submit an application. The intention-to-file letter must include a number of documents clearly specified in the Notice to Applicants. In particular, the following documentation must be provided.
o A copy of the proposed summary of product characteristics (SmPC);
o A justification of eligibility to use the centralized system (if not already requested)
o Proposed trade name(s) (the acceptability of the proposed trade name should be sought earlier; this is usually a single name);
o Legal basis of the application
o Details of the dosage form(s), strength(s), and pack sizes
o Legal category
o Details of the site of manufacture and batch release of the active substance and finished product
o Whether the dossier includes any novel manufacturing approaches eg Design space or PAT.
The submission of the intention to file a letter initiates the procedure for the assignment of a rapporteur and co-rapporteur who will be in charge of the assessment of the application. The rapporteur and co-rapporteur are responsible for putting together the assessment team which includes experts from the European experts' list held at the EMEA and utilizes resources from the national agencies.
The 2005 legislation no longer refers to the selection of the rapporteurs based on the applicant’s preferences or equal distribution of workload, as was the case in the previous legislation. The appointment of rapporteurs is based on objective criteria such as the use of the best available expertise in the relevant scientific area. The criteria and appointment process are detailed in EMEA guidance (EMEA 124066/2005). Potential rapporteurs must express their interest in undertaking the assessment at a CHMP/CVMP meeting; the selection of the rapporteurs’ rests with the CHMP/CVMP chairman.
(b) Evaluation Phase
The application is formally submitted to the EMEA, with copies to the rapporteur and co-rapporteur. The application is validated by the EMEA. Following successful validation, the applicant is asked to provide copies of the file/parts of the file to the other CHMP members and advised of the start date of the procedure.
o The rapporteur and co-rapporteurs appointed experts to evaluate the application and prepare a preliminary assessment report (PAR)
o The PAR and a preliminary List of Questions (LoQ) are dispatched to CHMP members for comments and the EMEA. The EME provides the applicant with a copy of these documents around 80. The CHMP adopts the final LoQ after receipt of comments and overall preliminary conclusions and review of the application within 120 days. These conclusions and questions are sent to the applicant by the EMEA.
The time clock is stopped until the applicant responds (normally 3 months, but not longer than 6 months).
o Following the applicant’s response, the rapporteurs prepare a joint report on the applicant’s response and identify any outstanding issues requiring the clock to be stopped a second time for the applicant to prepare a written response or oral presentation (hearing). The CHMP issued a final opinion on the application which must be undertaken within a total of 210 days.
o If the opinion is unfavorable, the company may give notice of its intention to appeal within 15 days and must submit the appeal within 60 days. The CHMP considers the appeal and issues an opinion within 60 days. A second appeal committee does not exist but different rapporteur(s) will be selected for the appeal assessment.
(c) Draft Decision
o Within 27 days, the CHMP opinion is transmitted to the Commission, the Member States, and the applicant, together with the AR and translations of the SmPC, labeling and package insert (provided by the applicant) into all Community languages, Norwegian and Icelandic.
o Within 15 calendar days after receipt of the opinion, the Commission prepares a draft decision which is forwarded to the Standing Committee.
(d) The Standing Committee Phase
o Member States have 22 days to forward their opinion on the decision to the Standing Committee.
o The Standing Committee (Member States representatives) has to formulate a decision. If there are no objections from the Member States the draft decision is progressed through this stage by means of the so-called ‘written procedure’. A qualified majority is required for a favorable decision (the number of ‘votes’ depends upon the size of the Member State). The Standing Committee can call a meeting to discuss the application, but this is very unusual.
o In the unusual case of no qualified majority in favor of the draft decision, the Council will get involved to reach a decision.
(e) Adoption and Notification
A signature of the Directorate General of DG Enterprise is required before the MA holder is notified about the final decision. This should take 15 days.
(f) Publication of the Decision
The decision is published in the Official Journal and is binding on all Member States. For Norway and Iceland, an identical national MA is granted following the Commission decision.
The EPAR (European Public Assessment Report), which is based on the CHMP AR, is made publicly available through the Internet on the EMEA website.
The 2004 Regulation gas also resulted in the publication of details of withdrawn applications.
