Regulatory pathways for Registration of Pharmaceuticals for Human Use - European Union

Regulatory pathways for Registration of Pharmaceuticals for Human Use - European Union
There are currently four different procedures that can be used to submit a medicinal product for marketing approval in the European Union.
Centralized Procedure (CP)
Mutual Recognition Procedure (MRP)
Decentralized Procedure (DCP)
National procedure1.Centralized procedure: The Centralsied Procedure is administered by the European Medicines Agency (EMA). It consists of a single application which, when approved, grants marketing authorisation for all markets within the European Union.
Mandatory for the Centralised Procedure:
Biotechnological medicinal products
Orphan medicinal products
New active substances for which the therapeutic indication is the treatment of
– Diabetes
– Cancer
– Acquired immune deficiency syndrome (HIV)
– Neurodegenerative disorder (Alzheimer, …)
– Auto-immune diseases and other immune dysfunctions
– Viral diseases
Optional for the Centralised Procedure
New active substances
Innovative medicinal products
In the interests of patients at Community level
– Pandemic
– Generic medicinal products of nationally authorised reference medicinal products
– OTC medicinal products
Generic medicinal products of reference medicinal products authorised by the CPFurther Information: Centralized Procedure
2.Mutual Recognition Procedure (MRP):The MRP has been in place in the EU since 1995. The objective of this procedure is to obtain marketing authorizations in one or several Member States, when the medicinal product has already been granted authorization by at least one country in the European Community.
Where the medicinal product has already received in a MS a MA at the time of application.
The applicant requests one or more CMS(s)[Concerned member state] to mutually recognize the authorization granted by the RMS[Reference Member State]. Within 90 days of receipt of a valid application by the RMS, the RMS provides the Assessment Report, or if necessary, updates any existing one and sends it together with other documents to the CMS(s) and to the applicant. The RMS launches the clock after receipt of the Assessment Report and validation of the application by each of the CMS(s). Within 90 days, the CMS(s) recognizes the decision of the RMS. Thirty days after the close of the procedure; the competent authorities of the CMS(s) adopt a decision and grant marketing authorization. At the end of the MRP with a positive agreement, a national marketing authorization will be issued to each of the CMS(s).
Mutual recognition means that EU countries may approve the decision made about a medicinal product by another EU country. The pharmaceutical company submits their application to the country chosen to carry out the investigative work, which then approves or rejects the application. The other countries have to decide within 90 days whether they approve or reject the decision made by the original country.
The mutual recognition procedure is based on that medicines are evaluated and approved by a Reference Member State (RMS) followed by a 90-day period where the Concerned Member States (CMS) consider the RMS assessment report. If the CMS agree with the assessment they should issue a marketing authorisation within 120 days from the start of the procedure.
Further Information: Mutual Recognition Procedure

3. Decentralized Procedure (DCP): The new DCP came into effect in the EU in 2005. The objective of this procedure is to obtain marketing authorizations in several Member States, when no marketing authorization has been granted in the European Community.
Where the medicinal product has not received in a MS a MA at the time of application.
The applicant should send an application to the competent authorities of each of the Member States, where there is intent to obtain a marketing authorization. The RMS (Reference Member State) will start the procedure after the application is determined to be complete by both the RMS and all the CMS(s).
The RMS forwards a preliminary Assessment Report on the dossier to the CMS(s) and the applicant within 70 days. The CMS(s) is asked to give comments on the proposed national prescription status and to inform the RMS.
On day 105, the RMS will forward all comments to the applicant and stops the clock if necessary, until the applicant prepares a response document. The RMS prepares a Draft Assessment Report on day 120 and may close the procedure if a consensus has been reached between the CMS(s) and the RMS. Otherwise; the CMS(s) has 90 more days to approve the Draft Assessment Report and other documents. Competent authorities of the RMS and the CMS(s) adopt a decision within 30 days after acknowledgement of their agreement to the Assessment Report and other documents.
At the end of the Decentralized Procedure with a positive agreement, a national marketing authorization will be issued to the RMS and each of the CMS(s).


Further Information: Decentralized Procedure Member State's SOP


4. National procedure: Independent national procedures will continue, but are strictly limited from 1 January 1998 to the initial phase of mutual recognition (granting of the marketing authorisation by the Reference Member State) and to medicinal products which are not to be authorised in more than one Member State.
Independent national procedures can also be used for extensions of authorized medicinal products as far as no a priori harmonization has been achieved for the initial marketing authorisation.


Scope of MRP/DCP/National Procedures:

New active substances (if not mandatory for the centralised procedure)
Generic medicinal products to national (and centralised) authorised reference medicinal products (if not a biotechnological medicinal product)
Informed consent applications
Well established use (WEU) (bibliographic applications) Special Types:

a. Repeat Use Marketing Authorization
b. Duplex Marketing Authorization
c. Parallel Imports Authorization
a. Repeat Use Marketing Authorization: A Marketing Authorisation Holder (MAH) can use the Mutual Recognition Procedure (MRP) for the same authorisation more than once after completion of a first MRP or a Decentralised Procedure (DCP)for the recognition of a marketing authorisation by other Member States (MS).
This procedure can be used in the following situations:

either by application to new Concerned Member States (CMS) not involved in the first MRP or DCP
or by reapplication to CMS withdrawn from the first procedure.Further Information: Procedural advice on Repeat Use

b. Duplex Marketing Authorization: A duplex marketing authorisation is a marketing authorisation for a product of which the dossier is identical to that of a product which is already authorised. In principle, this concerns a standard marketing authorisation, and the dossier must meet the known legal criteria. In a duplex marketing authorisation procedure, the MEB can waive a full evaluation, and the proof of authorisation (marketing authorisation) can be quickly issued.


Further Information: Duplex Marketing Authorization


c. Parallel Imports & Distribution:
Parallel Imports is issued by national competent authorities (Every country having own guidance for parallel imports) and Parallel distribution is issued by EMA.
Examples:
i. IMB (Irish Medicines Board): Parallel-importation is the importation from an EU Member State or a country within the EEA of a medicinal product which is therapeutically equivalent to a product already authorised in Ireland, by an importer who is someone other than the importer appointed by the marketing authorisation holder of the product on the Irish market.

The imported product may then be parallel-distributed in Ireland provided that the importer obtains an authorisation to market the product. An authorisation for a parallel-distributed product is identified by the letters 'PPA' in front of the authorisation number.

The IMB also operates a Dual-Pack Import Registration scheme. This applies to the parallel-import of a product which is identical in all respects to the product on the Irish market, and which is packaged in dual-market, identical packaging carrying the marketing authorisation numbers in both the source country and in Ireland. For parallel-imports which meet these criteria, a simplified registration process may be appropriate.