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Closure of EU manufacturing site

Arrangements in place for existing patients to complete their treatment

On 5 September 2014, the marketing authorisation holder for the advanced therapy medicine MACI (matrix applied characterised autologous cultured chondrocytes) closed the EU manufacturing site for the medicine, which is located in Denmark. Consequently, the licence of the manufacturing site was withdrawn. MACI is unavailable for new patients in the EU until a new manufacturing site has been registered in the EU. The closure was due to commercial reasons and the safety and effectiveness of MACI has not changed.

The European Medicines Agency has been working with the marketing authorisation holder since June 2014 to ensure that patients who had already started the treatment procedure were able to complete their treatment. A letter was sent to healthcare professionals informing them of the site closure and requesting that they notify the marketing authorisation holder of those patients who wish to complete their treatment. In addition, surgeons were asked not to start new patients on MACI.

Following the closure of the site, the marketing authorisation holder has been requested to store any remaining biopsies that have not yet been used to allow for potential later treatment with MACI, unless patients and their treating surgeons have explicitly indicated that they do not wish to complete treatment with MACI.

Information to patients
  • The EU manufacturing site for MACI has been closed for commercial reasons and the product will remain unavailable for new patients in the EU until a new manufacturing site has been registered. The safety and effectiveness of the product has not changed.
  • Patients who have already started treatment (i.e. those who have had their biopsies taken) should have been informed about the closure and should have discussed arrangements for completion of treatment with their treating surgeon.
  • The company has made arrangements to store any existing biopsies so that treatment can be completed unless patients and their treating surgeons explicitly indicated that they no longer wish to complete treatment with MACI.
Information to healthcare professionals
  • Surgeons and hospitals that have been using MACI were informed in June 2014 of the planned closure of the EU manufacturing site for MACI. The site has now been closed and MACI remains unavailable for new patients in the EU until a new manufacturing site has been registered in the EU.
  • The closure was due to commercial reasons and is not related to any change in the safety and effectiveness of MACI.
  • New patients should be treated with a suitable alternative and surgeons should not order new biopsy kits for MACI.
  • For patients who have already started treatment (i.e. those who have had their biopsies taken) company has made arrangements to store any existing biopsies so that treatment can be completed unless patients and their treating surgeons have explicitly indicated that they no longer wish to complete treatment with MACI.
More about the medicine

MACI is an implant used to repair cartilage defects at the ends of the bones of the knee joint. MACI is an advanced therapy medicinal product called a ‘tissue engineered product’. This is a type of medicine containing cells or tissues that have been manipulated so that they can be used to repair, regenerate or replace tissue.

MACI was on the market since 1998 in individual EU countries according to national procedures. It was subsequently evaluated through the European Medicines Agency to comply with the EU regulation on advanced therapies, which requires all advanced therapies in EU Member States to undergo an evaluation by the Agency in order to obtain an EU-wide marketing authorisation; this was obtained in 2013. Since 2013 MACI has been marketed in Denmark, Greece and the UK.

More about the closure of the manufacturing site

Following the closure of the manufacturing site and because EU legislation1 requires authorised medicines to have a registered manufacturing site, a review was initiated at the request of the European Commission on 10 September 2014 (under Article 20 of Regulation (EC) No 726/2004) to determine whether the marketing authorisation for MACI should be suspended or revoked.

Because MACI is an advanced therapy medicine, the review was carried out by the Committee on Advanced Therapies (CAT), and was subsequently endorsed by the Committee for Medicinal Products for Human Use (CHMP), which is responsible for questions concerning medicines for human use. Based on the draft opinion adopted by the CAT, the CHMP adopted a final opinion on 25 September 2014, recommending the suspension of the marketing authorisation for MACI until a new manufacturing site is registered in the EU. The final opinion was sent to the European Commission, which issued a legally binding decision on 19 November 2014.


1 Article 118 of Directive 2001/83/EC, which specifies that a marketing authorisation must be suspended in case any one of the requirements laid down in Article 41 (such as the need for a manufacturing site) is no longer met.

Name Language First published Last updated
Maci Article-20 procedure - Closure of EU manufacturing site for Maci BG = bălgarski 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci ES = español 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci CS = čeština 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci DA = dansk 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci DE = Deutsch 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci ET = eesti keel 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci EL = elliniká 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci EN = English 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci FR = français 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci IT = italiano 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci LV = latviešu valoda 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci LT = lietuvių kalba 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci HU = magyar 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci MT = Malti 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci NL = Nederlands 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci PL = polski 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci PT = português 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci RO = română 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci SK = slovenčina 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci SL = slovenščina 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci FI = suomi 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci SV = svenska 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci HR = Hrvatski 2014-09-26 2014-12-17

Key facts

Approved nameMaci
International non-proprietary name (INN) or common name

matrix-applied characterised autologous cultured chondrocytes

Associated names
ClassAdvanced therapies
Reference numberEMEA/H/A20/1409/C/002522/0004
TypeArticle 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of manufacturing or safety issues.

StatusEuropean Commission final decision
Opinion date25/09/2014

All documents

Name Language First published Last updated
Maci Article-20 procedure - Notification (English only) 2014-09-26  
Maci Article-20 procedure - Closure of EU manufacturing site for Maci BG = bălgarski 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci ES = español 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci CS = čeština 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci DA = dansk 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci DE = Deutsch 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci ET = eesti keel 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci EL = elliniká 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci EN = English 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci FR = français 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci IT = italiano 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci LV = latviešu valoda 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci LT = lietuvių kalba 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci HU = magyar 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci MT = Malti 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci NL = Nederlands 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci PL = polski 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci PT = português 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci RO = română 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci SK = slovenčina 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci SL = slovenščina 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci FI = suomi 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci SV = svenska 2014-09-26 2014-12-17
Maci Article-20 procedure - Closure of EU manufacturing site for Maci HR = Hrvatski 2014-09-26 2014-12-17
Maci Article-20 procedure - Assessment report (English only) 2014-12-17  
Maci Article-20 procedure - Annex I BG = bălgarski 2014-12-17  
Maci Article-20 procedure - Annex I ES = español 2014-12-17  
Maci Article-20 procedure - Annex I CS = čeština 2014-12-17  
Maci Article-20 procedure - Annex I DA = dansk 2014-12-17  
Maci Article-20 procedure - Annex I DE = Deutsch 2014-12-17  
Maci Article-20 procedure - Annex I ET = eesti keel 2014-12-17  
Maci Article-20 procedure - Annex I EL = elliniká 2014-12-17  
Maci Article-20 procedure - Annex I EN = English 2014-12-17  
Maci Article-20 procedure - Annex I FR = français 2014-12-17  
Maci Article-20 procedure - Annex I IT = italiano 2014-12-17  
Maci Article-20 procedure - Annex I LV = latviešu valoda 2014-12-17  
Maci Article-20 procedure - Annex I LT = lietuvių kalba 2014-12-17  
Maci Article-20 procedure - Annex I HU = magyar 2014-12-17  
Maci Article-20 procedure - Annex I MT = Malti 2014-12-17  
Maci Article-20 procedure - Annex I NL = Nederlands 2014-12-17  
Maci Article-20 procedure - Annex I PL = polski 2014-12-17  
Maci Article-20 procedure - Annex I PT = português 2014-12-17  
Maci Article-20 procedure - Annex I RO = română 2014-12-17  
Maci Article-20 procedure - Annex I SK = slovenčina 2014-12-17  
Maci Article-20 procedure - Annex I SL = slovenščina 2014-12-17  
Maci Article-20 procedure - Annex I FI = suomi 2014-12-17  
Maci Article-20 procedure - Annex I SV = svenska 2014-12-17  
Maci Article-20 procedure - Annex I HR = Hrvatski 2014-12-17  
Maci Article-20 procedure - Annex II BG = bălgarski 2014-12-17  
Maci Article-20 procedure - Annex II ES = español 2014-12-17  
Maci Article-20 procedure - Annex II CS = čeština 2014-12-17  
Maci Article-20 procedure - Annex II DA = dansk 2014-12-17  
Maci Article-20 procedure - Annex II DE = Deutsch 2014-12-17  
Maci Article-20 procedure - Annex II ET = eesti keel 2014-12-17  
Maci Article-20 procedure - Annex II EL = elliniká 2014-12-17  
Maci Article-20 procedure - Annex II EN = English 2014-12-17  
Maci Article-20 procedure - Annex II FR = français 2014-12-17  
Maci Article-20 procedure - Annex II IT = italiano 2014-12-17  
Maci Article-20 procedure - Annex II LV = latviešu valoda 2014-12-17  
Maci Article-20 procedure - Annex II LT = lietuvių kalba 2014-12-17  
Maci Article-20 procedure - Annex II HU = magyar 2014-12-17  
Maci Article-20 procedure - Annex II MT = Malti 2014-12-17  
Maci Article-20 procedure - Annex II NL = Nederlands 2014-12-17  
Maci Article-20 procedure - Annex II PL = polski 2014-12-17  
Maci Article-20 procedure - Annex II PT = português 2014-12-17  
Maci Article-20 procedure - Annex II RO = română 2014-12-17  
Maci Article-20 procedure - Annex II SK = slovenčina 2014-12-17  
Maci Article-20 procedure - Annex II SL = slovenščina 2014-12-17  
Maci Article-20 procedure - Annex II FI = suomi 2014-12-17  
Maci Article-20 procedure - Annex II SV = svenska 2014-12-17  
Maci Article-20 procedure - Annex II HR = Hrvatski 2014-12-17  

Document description

  • Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
  • Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
  • List of the medicines affected by the referral (Annex I)
  • Scientific conclusions of the Committee (Annex II)

The following two documents are sometimes available:

  • Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes have been recommended by the Committee
  • Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be taken for the marketing authorisation(s) such as safety measures or extra studies

Current status:
European Commission final decision

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