Marketing Authorisation
Marketing Authorisation
There are several procedures available for the marketing authorisation of medicinal products. The type of marketing authorisation procedure depends on the medicine itself and whether the pharmaceutical company intends to market the medicinal product:
- only in Germany,
- in several member states of the European Union (EU) or the European Economic Area (EEA)
- throughout the European Union (EU) or the entire European Economic Area (EEA)
Medicinal products can be authorised by:
- national procedure
- mutual recognition procedure (MR procedure)
- decentralised procedure (DC procedure)
- centralised procedure
For the authorisation of certain drugs, in particular medicines with new active substances for severe diseases, the centralised European authorisation procedure must be used. The approval is granted by the European Commission. The centralised authorisation procedure can also be chosen optionally. If it is an innovative medicinal product and/or if it is in the public health interest, the medicinal product should be marketed throughout Europe (see Regulation (EC) No 726/2 004).
All other medicinal products not covered by Regulation (EC) No 726/2004 are authorised by the national authorities of the EU/EEA Member States, either in the national procedure or in the decentralised procedure. Products already approved in the EU/EEA must be authorised through a mutual recognition procedure. The evaluation of applications for authorisation is always carried out by the competent national authority (in Germany BfArM or PEI), irrespective of the procedure under which authorisation is granted.
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Centralised Procedure
Centralised Procedure
The centralised procedure is a European authorisation procedure that allows a marketing authorisation in all Member States of the European Economic Area (EEA) on the basis of only one application for authorisation. The legal basis for the centralised procedure is Regulation (EC) 726/2004.
The centralised procedure is mandatory for medicinal products
- which are produced by biotechnological methods (recombinant DNA, controlled gene expression in prokaryotes and eukaryotes, hybridomas and monoclonal antibodies),
- for novel therapies,
- for rare diseases,
- which cobtain new active substances for the treatment of cancer, neurodegenerative diseases, diabetes, acquired immunodeficiency syndrome, viral diseases, autoimmune diseases or other immune deficiencies (Article 3 (1) of Regulation (EC) 726/2004).
The centralised procedure is optional for medicinal products containing a new active substance that has not yet been authorised in the EU and is not intended for the above-mentioned indications or for medicinal products for which significant therapeutic, scientific or technical innovation can be demonstrated (Article 3 (2) of Regulation (EC) No 726/2004).
Interaction of European medicines agencies
Centralised procedures are co-ordinated by the European Medicines Agency (EMA). The scientific evaluation of the quality, efficacy and safety documentation to be submitted with the application for authorisation is carried out by the experts in the Member States.
For this purpose, the Committee for Medicinal Products for Human Use (CHMP) was established at the EMA and, for new therapies, the Committee for Advanced Therapies (CAT). Each Member State shall appoint one member and one representative to the panels. The Paul-Ehrlich-Institut (PEI) is represented on both panels because of its proven expertise in biological drugs.
For each application for authorisation, the CHMP will designate two CHMP members from each Member State as rapporteur or co-rapporteur, following an application procedurewho are responsible for preparing the scientific assessment report. This report will be commented on by the other CHMP members. In evaluating and commenting the assessment report, the CHMP members rely on the scientific expertise of the scientists in their national regulatory authorities. With its special expertise in gene and cell-based therapeutics, the CAT is responsible for the scientific evaluation of products and prepares the draft of a scientific opinion for final adoption by the Advanced Therapy Medicinal Products (ATMP) CHMP. The latter will prepare a final report with the recommendation for granting the marketing authorisaton or a rejection (Opinion).
Based on this recommendation, the European Commission decides on the authorisation of the medicinal product for all countries of the European Union. This decision is recognised by the states of the European Economic Area (EEA). A centrally authorised medicinal product can be marketed throughout the EEA. The decision of the European Commission and the European Public Assessment Report (EPAR) prepared by the EMA on the basis of the scientific opinion of the CHMP are publicly available.
Special Procedures
In justified exceptional cases, when patients shall have rapid access to new therapies, there is the option of an accelerated assessment under defined conditions or a conditional marketing authorisation or approval marketing authorisation under exceptional circumstances circumstances). Furthermore, in 2016, the EMA introduced a PRIME (Priority Medicines) procedure to better support the development of medicines for which there is a high medical need.
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Decentralised Procedure
Decentralised Procedure
The decentralised procedure (DCP) is based on the same basic idea as the Mutual Recognition Procedure (MRP), i.e. on the recognition of the quality, efficacy and safety of one Member State of the European Union (EU)/European Economic Area (EEA) by the other Member States involved in the procedure (Concerned Member States, CMS). However, in contrast to the MRP, the decentralised procedure does not require a national authorisation of the medicinal product. The pharmaceutical company simultaneously applies for a marketing authorisation in all the Member States where it intends to apply for such authorisation. The legal basis is Section 25b of the Medicinal Products Act or Art. 28-29 of Directive 2001/83/EC.
Interaction between RMS and CMS
In consultation with the pharmaceutical company, one of the Member States participating in the DCP assumes the role of Reference Member State (RMS). The competent authority of the RMS carries out the scientific evaluation of the medicinal product on behalf of the other Member States involved (CMS), prepares the assessment report, and coordinates the procedure. The CMS may already provide comments on the draft of the assessment report. At the end of the procedure (no later than day 210), the CMS shall agree to the final assessment report unless they hold the view that granting a marketing authorisation would present a serious risk to public health. In this case, a 60-day referral procedure follows in the Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) in accordance with Art. 27 of Directive 2001/83/EC. If this does not lead to an agreement either, the procedure is referred to the Committee for Human Medicinal Products (CHMP) at the European Medicines Agency (EMA). The decision on the authorisation of the medicinal product will then be taken by the European Commission on the basis of the opinion of the CHMP.
After completion of the DCP and examination of the national translations of the texts for the labelling of the packaging, the package leaflet, and the Summary of Product Characteristics (SmPC), the RMS and the CMS issue national marketing authorisations. After a DCP has been carried out once, the pharmaceutical company may later apply for marketing authorisations for the medicinal product concerned via the MRP in other EU/EEA Member States (repeat-use procedure). If the repeat-use procedure is to be used, this must be communicated to the Reference Member State in advance on a special form (see information on the "Mutual recognition procedure" tab).
After the marketing authorisation has been granted, the marketing authorisation holder must, in accordance with section 29 subsection 1b, 1c, and 1g of the AMG, fulfil the notification obligations regarding the placing on the market of the medicinal product (sunset clause).
The PEI is happy to provide consultation using its experience from the DCPs it has carried out so far, in particular as an RMS.
Further information on the DCP is available on the joint websites of the national regulatory authorities in the EU, the Heads of Medicines Agencies (HMA). The Coordination Group (CMDh) regularly develops and publishes relevant guidelines on this website.
Requests for Takeover of the RMS Function (DCP Slot Requests)
Please send requests for the PEI to take over the RMS function using the CMDh RMS Common request form (recommended) or informally via mail to eSubmission@pei.de. Your request should include at least the following information:
- Name of the medicinal product, active substance, information on strengths and dosage forms,
- Information on Concerned Member States,
- Planned submission date,
- Information on whether other NCAs have already been requested to take over the RMS function and, if available, their response.
The subject of the email should include at least the following information:
DCP Slot Request - Drug Name - Active Ingredient
Alternatively, a corresponding request can also be made during a national scientific advice procedure.
Application
The application documents must be submitted electronically using the electronic common technical document (eCTD) format via the Common European Submission Platform (CESP).
The application for authorisation of a medicinal product in the DCP must use the electronic application form (eAF). For the cover letter, the PEI is requesting you to use the CMDh template.
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Mutual Recognition Procedure
Mutual Recognition Procedure
The Mutual Recognition Procedure (MRP) allows the pharmaceutical company to obtain a marketing authorisation for a medicinal product that has already been nationally authorised in a Member State of the European Union (EU) / European Economic Area (EEA), known as the Reference Member State (RMS), on the basis of the examination and assessment of the quality, efficacy and safety of that Member State by other participating Member States (Concerned Member States – CMS). The MRP is mandatory if an authorisation for the medicinal product already exists in a European Member State. The legal basis is Section 25b of the German Medicinal Products Act (AMG) or Art. 28-29 of the Directive 2001/83 / EC.
Interaction between RMS and CMS
The competent authority of the RMS shall make its assessment report on the quality, efficacy and safety of the medicinal product available to the Member States participating in the MRP (CMS) and shall coordinate the procedure between the pharmaceutical company and the participating Member States. The CMS shall accept the assessment by the RMS within 90 days unless they hold the view that the product would present a serious risk to public health. If that case, a 60-day referral procedure will follow in the Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) pursuant to Article 27 of Directive 2001/83/EC. If an agreement is still not reached, the procedure will be referred to the Committee for Human Medicinal Products (CHMP) at the European Medicines Agency (EMA). The decision on the authorisation of the medicinal product will then be taken by the European Commission on the basis of the opinion of the CHMP.
After completing the MRP and reviewing the translations of the labelling, package insert and Summary of Product Characteristics (SmPC) texts into the national languages, the CMS will issue national marketing authorisations.
Repeat Use Procedure
Once an MRP (or a DCP) is performed, it may be followed later by other MRPs for obtaining an authorisation in other member states of the European Union (EU) and the European Economic Area (EEA) (Repeat Use Procedure, RUP). If this procedure is to be used, the Reference Member State shall be notified in advance using a special form (see link below under Further Information).
Zero Day Procedure
In exceptional cases, to alleviate shortages or problems with access to critical medicinal products in Member States, repeat use procedures (RUP) or a mutual recognition procedure (MRP) with a shortened timetable may be implemented. Applicants are reminded that these shortened “administrative” procedures are only to be used if the newly admitted Concerned Member States (CMS) do not consider the standard timetable to be appropriate. The CMDh's instructions for “Zero day MR procedures” must be observed.
Guidance Documents
The Paul-Ehrlich-Institut (PEI) has many years of experience in MRPs, in particular as an RMS, and gladly provides its expertise for consultations on the topic.
Further information on the MRP is available on the joint website of the national regulatory authorities in the EU, the Heads of Medicines Agencies (HMA). The Coordinating Group (CMDh) regularly prepares and publishes corresponding guidelines on this website.
Comprehensive information on pharmaceutical legislation at the European level can be found on the website of the European Commission’s Directorate-General for Health and Consumers ("EudraLex").
Submitting an Application
The implementation of an MRP or RUP must be requested in advance from the RMS using the CMDh "Request for MRP/RUP/Update assessment report" form (see link below under Further Information).
Please send the completed form by email to: eSubmission@pei.de.
The electronic application form (eAF) must be used when applying for authorisation of a medicinal product via the MRP or RUP. The PEI requests that you use the CMDh template for the cover letter.
The application documents must be submitted electronically using the electronic common technical document (eCTD) format. We strongly advise that you submit the application via the Common European Submission Platform (CESP).
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National Procedure
National Procedure
In the national procedure pursuant to Sections 21et seq. of the German Medicinal Products Act (AMG), the Paul-Ehrlich-Institut (PEI) assesses the quality, efficacy and safety of medicinal products for which a marketing authorisation application has been submitted, independently of other European regulatory authorities. This type of procedure is normally only an option for medicinal products that are not yet authorised in a Member State of the European Union (EU) or the European Economic Area (EEA).
If the pharmaceutical manufacturer already has an authorisation for the medicinal product in another EU/EEA Member State, a marketing authorisation shall be carried out by means of the Mutual Recognition Procedure (MRP).
If the medicinal product is not authorised in the EU/EWR and is to be marketed not only in Germany but also in other EU / EEA Member States, the decentralised procedure (DCP) must be applied.
A special form of national marketing authorisation exists for medicinal products imported in parallel (simplified procedure).
Electronic submission of an application
The application documents must be submitted electronically using the electronic common technical document (eCTD) format. Applications are to be submitted via the Common European Submission Platform (CESP).
The electronic application form (eAF) must be completed when applying for authorization of a medicinal product via the national procedure.
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