Product Authorizations in the EU/EEA
Product Authorizations in the EU/EEA
- November 23, 2020
- Posted by: Manoj Swaminathan
Very frequently do the Pharmacovigilance professionals come across terms such as RMS, MRP/DCP, CAP, CMS, etc., while interacting with the colleagues from the regulatory department. All these concepts are good to know, and are definitely relevant, as Pharmacovigilance requirements may vary across each of these terms. Besides, this is applicable to both human and veterinary medicinal products.
It is first essential to know the following abbreviations;
RMS: Reference Member State
CMS: Concerned Member States
MRP: Mutually Recognized Product
DCP: Decentralized Procedure
CAP: Centrally Authorized Product
NAP: National Authorized Product
EU/EEA: European Union/European Economic Area
MAH: Marketing Authorization Holder
HMA: Heads of Medicines Agencies
A product may be authorized in one of the following procedures, in the EU/EEA.
1. National Procedure
2. Mutual Recognition
3. Decentralized Procedure, and
4. Centrally Authorized Procedure
Centrally Authorized Procedure
There is a single authorization for all of the member states in EU/EEA. MA number is common across all the member states.
Which products qualify for Central Authorisation in EU?
- Products derived from biotechnology
- Orphan medicinal products
- Medicinal products for human use which contain an active substance authorised in the Union after 20 May 2004 and which are intended for the treatment of AIDS, cancer, neurodegenerative disorders or diabetes.
- All medicinal products that contain an active substance not authorised before 20 May 2004, or constitute a significant therapeutic scientific or technical innovation, or for which an EU authorisation would be in the interest of patients.
This pertains to country-specific authorization where the MAH can commercialize the product only in that member state. A National Marketing Authorization is initially valid for five years from the date of first authorization. At the end of the five year period, it will be subject to renewal, which is a mechanism for reviewing the product to ensure the benefit/risk balance remains favourable. This review takes into consideration any further information obtained about the product from the experience gained of its use since it was first authorized, e.g. pharmacovigilance data. This is to ensure that the product’s MA is still appropriate. Following this review, the MA will be valid indefinitely, or the MAH will be asked to submit another renewal in a further five year’s time.
Mutual Recognition and Decentralized Procedure
A product needs to be already authorized in at least one Member State on a national basis in order for MRP to be used. However, DCP may be used if the product is not already authorized in any Member State. This is mainly when the MAH does not want to use the centralized procedure, or the product is not eligible for the centralized procedure.
MRI Product Index
This is a free online resource from HMA, for finding information on the MRP/DCP in EU/EEA.
During the transition period (Feb-Dec 2020), the UK will not be able to act as RMS in MRP/DCP, but the UK can participate in MRP/DCP as CMS.
Compassionate use does not relate to any kind of authorization in the European Union, although the product may be authorized in another member state. It is important to know this, as certain products may be supplied through this route. Compassionate use is a treatment option that allows the use of unauthorised medicine.
Under strict conditions, products in development can be made available to groups of patients who have a disease with no satisfactory authorised therapies and who cannot enter clinical trials. In the European Union, these programmes are only put in place if the medicine is expected to help patients with life-threatening, long-lasting or seriously debilitating illnesses, which cannot be treated satisfactorily with any currently authorised medicine.
1. Harmonization of SmPC/PIL, including Safety Variations – E.g., for generic products, when MAH needs to consider harmonization in-line with the innovator in RMS Country.
2. PSUR Submissions – E.g., Six-monthly (or less frequent) requirements may be specified in the MA grant letter. Submissions will be required to all the CMS countries, and not only the RMS. Besides, there may be specifications in EURD for NAP.
3. Risk Management Plan – E.g., Await comments from all the CMS countries
4. Inspections in EU/EEA – E.g., More frequent for CAP
5. Safety Data Exchange Agreement – E.g., if there are partner companies for commercialization in CMS, or even in RMS. This may also be relevant for compassionate use.
6. Exploitant (France) – E.g., if the RMS or the CMS is France, then one may need to consider an Exploitant as well.
7. Cross-Reporting to Eudravigilance – E.g., when cross-reporting of Serious case reports from outside EU/EEA should start immediately after EoP.