Referrals

Referrals are a set of procedures used when EU member states have not reached consensus on decisions regarding medicinal products. A referral may be initiated by a single member state, the European Commission or the marketing authorisation holder (MAH).

It can apply to a specific product, substance or product class and the product affected may have been authorised via the central, national or decentralised procedure or through the mutual recognition procedure. As a rule, cases are referred to the European Medicines Agency's Scientific Committee for Medicinal Products for Human Use (CHMP) and the European Medicines Agency's Scientific Committee for Veterinary Medicinal Products (CVMP), which are assigned to perform the scientific evaluation for all Member States concerned.

However, cases concerning the safety of medicinal products for human use are handled by the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC). Concerning matters of safety, which include at least one product approved through the centralised procedure, it is the European Commission that takes the formal decision based on the position of the PRAC. If there are no products approved through the centralised procedure, the Co-ordinating Group for Mutual Recognition Decentralised Procedures – Human (CMDh) – shall present a standpoint (CMDh position) by consensus or majority.

If the position is reached by consensus it applies as a formal decision. If the position is reached by majority the European Commission shall make the formal decision. For other referrals the formal decision is taken by the European Commission after obtaining an opinion from the CHMP (CHMP opinion). The opinion can be re-examined (once again by PRAC/CHMP/CVMP).

Overall Process for Referrals

(Click for larger image)

Process of refferrals

Different Types of Referrals

Safety, quality, production and efficacy
Article 20
EC/726/2004 
This procedure applies for medicinal products that undergo the centralised procedure in issues regarding the manufacturing or safety of medicinal products.
Article 31 2001/83/EC,article 35
2001/82/EC
This procedure is applied on cases affecting common EU interests regarding the quality, safety or efficacy of medicinal products.
Medicinal products for children
Article 107i
2001/83/EC 
This procedure can be initiated by a member state or the European Commission if urgent action is deemed necessary based on safety data. For example, in cases where it is considered  to temporarily suspend or revoke the marketing authorisation, to prohibit the supply of a medicinal product or to reject a renewal application, and in cases where the company has cancelled the market release or has taken action to withdraw an authorisation and also in cases where a new contraindication, reduction in the recommended dose or restriction of the indications is required.
Medicinal products for children
Article 29
EC/1901/2006 
This procedure can be initiated by MAH when applying for a new indication, new pharmaceutical form or new route of administration for use by children for products authorised under EU Directive 2001/83/EC.
Medicinal products authorised through the mutual recognition procedure (MRP) and the decentralised procedure (DCP)
Article 13
EC/1234/2008 
This procedure is applicable when there is a disagreement between member states regarding ongoing cases of variation type II.
Article 29(4) 2001/83/EC,  article
33
2001/82/EC
This procedure is applicable concerning decisions in MRP when there is a disagreement between member states about the potential serious risk to public health in ongoing cases of e.g. renewal and new application.
Article
30 2001/83/EC,
article
34
2001/82/EC
This procedure is applicable when member states have adopted different approval decisions on a medicinal product for which harmonised summaries of product characteristics should be prepared(e.g. different indications, contraindications).

 

  

National Decisions arising from Rulings in Referrals

The Swedish Medical Products Agency (MPA) shall make a decision in accordance with the unified position in referrals or the decision following the Commission's ruling in cases where an agreement could not be reached (see Sections 6 a and b of the Medicinal Products Act (1992:859) and Sections 6 – 13 of Chapter 3 of the Medicinal Product Regulation (2006:272). In cases where changes are required the MAH shall submit the variation applications that are necessary for the MPA  to make the decision following the ruling in the referral (cf. the Commission's detailed guidelines for the different categories of variations to the terms of marketing authorisations for medicinal products for human and veterinary use (2010/C 17/01)). The MAH is urged at an early stage following the completion of a referral to contact the MPA if there are questions about what action the holder should take.
Information when national products undergo MRP

When national products undergo MRP the authorisation may need to be adjusted regarding Asp No. and MT number in order to maintain the harmonisation of the product information. Contact the MPA on RIC@mpa.se for questions related to existing Asp No. for national products and the registration of new ones for MRP.

Information regarding product information

The latest approved version of the product information must be updated in accordance with the texts established by Commission decision. The product information must be attached in Word format to the variation application or the original case in question. Amendments to the text must be shown using the "Track Changes" function in Word.

For the national procedure Swedish product information shall be attached.

For DCP the English (common) and the Swedish versions of the product information shall be attached by the MAH.  If the product will not be placed on the market in Sweden this shall be notified by the MAH instead of attaching Swedish product information. The English version shall however still be attached to the variation application or the original case.
Mock-ups
In electronic applications mock-ups are attached in PDF version 1.4 or preferably 1.7 in order for them to be eligible for electronic storage.

In cases where the outcome of the referral affects the name, strength, pharmaceutical form and/or target species for products already on the market, new packaging may need to be put on the market on the same date that the application for the variation is approved. In such cases this must be notified in the letter accompanying the application for the variation or the original case since the date of approval may need to be adjusted.

 
 
 

Swedish Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, SWEDEN | +46 18 17 46 00 | registrator@lakemedelsverket.se | Contact information