Symbioflor 2

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EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome

Medicine should no longer be used for other disorders of the gut

On 22 June 2017 a review by European Medicines Agency (EMA) concluded that Symbioflor 2 and associated names can continue to be used for treatment of irritable bowel syndrome (IBS) in adults. However, the medicine should no longer be used more widely to treat so-called functional gastrointestinal disorders, a group of disorders with a variety of causes that may require different treatment approaches.

Symbioflor 2, which contains Escherichia coli bacteria, has been described as a probiotic, which means that it encourages the growth of beneficial organisms (‘flora’) in the gut. It was first made available in Germany in the 1950s and subsequently in Austria and Hungary.

In reaching its conclusions, EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed all available evidence on the effectiveness and safety of Symbioflor 2. The data included clinical studies, scientific publications, post-marketing experience, as well as information provided by the company and the views of an expert group formed for evaluating Symbioflor 2. The review did not find any new evidence on the effectiveness of Symbioflor 2 since the product was last approved. Available evidence suggests that the risk of harm from Symbioflor 2 is low.

A randomised study involving around 300 adults suggested that Symbioflor 2 was effective for treating IBS. However, the study had weaknesses. Benefit has not yet been established in children with IBS. Since the available data were not sufficiently robust for the CHMP to draw conclusions on how well Symbioflor 2 works and whether it is effective for any particular type of IBS, the CHMP has asked the company to carry out a well-designed study on effectiveness and safety among patients with different features of IBS (e.g. those with diarrhoea or with constipation as an important feature). Submission of the study report to national authorities will be a condition for maintaining Symbioflor 2’s marketing authorisation.

The company that markets Symbioflor 2 did not submit data to support its use in ‘functional gastrointestinal disorders’ and agreed to remove this use from the medicine’s authorisation. The CHMP recommendation was sent to the European Commission which issued a legally binding decision valid throughout the EU.

Information for patients

You can continue to take Symbioflor 2 for treating symptoms of irritable bowel syndrome by following the information in the medicine’s revised package leaflet.

  • Speak with a pharmacist or your doctor if you have any problems affecting your stomach or gut. You should not use Symbioflor 2 for conditions affecting the gut other than irritable bowel syndrome.
  • Speak with a pharmacist or your doctor if your symptoms of irritable bowel syndrome do not improve with Symbioflor 2 or if they get worse.
  • If you have any questions or concerns, speak with a pharmacist or your doctor.
Information for healthcare professionals

Symbioflor 2 should be used for the treatment of irritable bowel syndrome (IBS) only, and it should no longer be used for treating ‘functional gastrointestinal disorders’ or other conditions of the gastrointestinal tract.

  • A study comparing Symbioflor 2 with placebo suggested that it was effective at treating IBS in adults. However, the study had some weaknesses and it did not provide evidence on how well Symbioflor 2 works in different types of IBS.
  • The company will need to carry out a well-designed study to demonstrate the efficacy and safety of Symbioflor 2 for treating different variants of IBS, as a condition for continuing to market it.
  • An observational study involving adolescents and children aged over 4 years did not provide sufficient evidence of efficacy and safety in children and adolescents.
  • The safety profile of Symbioflor 2 is acceptable.
  • The product information will be updated in line with this review of Symbioflor 2.
More about the medicine

Symbioflor 2 and associated names contains Escherichia coli bacteria some of which have been broken down (autolysed) while others are living. It is marketed in some European Union countries for treating irritable bowel syndrome, functional gastrointestinal diseases and some other gastrointestinal disorders and for regulating the immune system.

Medicines containing Escherichia coli are available as oral drops in Austria, Germany and Hungary under the following invented names: Symbioflor 2, Symbioflor E. Coli and Symbioflor Escherichia.

The medicine has been described as probiotic, which means that it encourages the growth of beneficial organisms (‘flora’) in the gut. Escherichia coli bacteria form part of the normal gut flora. The way it works in irritable bowel syndrome is not fully understood.

More about the procedure

The review of Symbioflor 2 (and associated names) was initiated on 30 March 2016 at the request of Germany, under Article 31 of Directive 2001/83/EC.

The review was carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which adopted the Agency’s opinion. The CHMP opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 28/08/2017.

Name Language First published Last updated
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome BG = bălgarski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome ES = español 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome CS = čeština 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome DA = dansk 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome DE = Deutsch 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome ET = eesti keel 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome EL = elliniká 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome EN = English 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome FR = français 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome IT = italiano 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome LV = latviešu valoda 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome LT = lietuvių kalba 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome HU = magyar 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome MT = Malti 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome NL = Nederlands 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome PL = polski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome PT = português 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome RO = română 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome SK = slovenčina 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome SL = slovenščina 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome FI = suomi 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome SV = svenska 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome HR = Hrvatski 2017-06-23 2017-09-07

Key facts

Approved nameSymbioflor 2
International non-proprietary name (INN) or common name

Escherichia coli bacteria (cells and autolysate)

Associated namesSymbioflor E. Coli, Symbioflor® 2, Symbioflor Escherichia
ClassOther immunostimulants, Antidiarrheal microorganisms
Reference numberEMEA/H/A-31/1441
TypeArticle 31 referrals

This type of referral is triggered when the interest of the Community is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

StatusOpinion provided by Committee for Medicinal Products for Human Use
Opinion date

All documents

Name Language First published Last updated
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome BG = bălgarski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome ES = español 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome CS = čeština 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome DA = dansk 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome DE = Deutsch 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome ET = eesti keel 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome EL = elliniká 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome EN = English 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome FR = français 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome IT = italiano 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome LV = latviešu valoda 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome LT = lietuvių kalba 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome HU = magyar 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome MT = Malti 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome NL = Nederlands 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome PL = polski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome PT = português 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome RO = română 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome SK = slovenčina 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome SL = slovenščina 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome FI = suomi 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome SV = svenska 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - EMA recommends that Symbioflor 2 can continue to be used for irritable bowel syndrome HR = Hrvatski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - CHMP assessment report (English only) 2017-09-07  
Symbioflor 2 Article-31 referral - Annex I BG = bălgarski 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I ES = español 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I CS = čeština 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I DA = dansk 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I DE = Deutsch 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I ET = eesti keel 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I EL = elliniká 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I EN = English 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I FR = français 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I IT = italiano 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I LV = latviešu valoda 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I LT = lietuvių kalba 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I HU = magyar 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I MT = Malti 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I NL = Nederlands 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I PL = polski 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I PT = português 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I RO = română 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I SK = slovenčina 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I SL = slovenščina 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I FI = suomi 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I SV = svenska 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex I HR = Hrvatski 2016-04-06 2017-09-07
Symbioflor 2 Article-31 referral - Annex II BG = bălgarski 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II ES = español 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II CS = čeština 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II DA = dansk 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II DE = Deutsch 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II ET = eesti keel 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II EL = elliniká 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II EN = English 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II FR = français 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II IT = italiano 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II LV = latviešu valoda 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II LT = lietuvių kalba 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II HU = magyar 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II MT = Malti 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II NL = Nederlands 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II PL = polski 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II PT = português 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II RO = română 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II SK = slovenčina 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II SL = slovenščina 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II FI = suomi 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II SV = svenska 2017-09-07  
Symbioflor 2 Article-31 referral - Annex II HR = Hrvatski 2017-09-07  
Symbioflor 2 Article-31 referral - Annex III BG = bălgarski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III ES = español 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III CS = čeština 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III DA = dansk 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III DE = Deutsch 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III ET = eesti keel 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III EL = elliniká 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III EN = English 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III FR = français 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III IT = italiano 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III LV = latviešu valoda 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III LT = lietuvių kalba 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III HU = magyar 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III MT = Malti 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III NL = Nederlands 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III PL = polski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III PT = português 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III RO = română 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III SK = slovenčina 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III SL = slovenščina 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III FI = suomi 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III SV = svenska 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex III HR = Hrvatski 2017-06-23 2017-09-07
Symbioflor 2 Article-31 referral - Annex IV BG = bălgarski 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV ES = español 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV CS = čeština 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV DA = dansk 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV DE = Deutsch 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV ET = eesti keel 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV EL = elliniká 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV EN = English 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV FR = français 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV IT = italiano 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV LV = latviešu valoda 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV LT = lietuvių kalba 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV HU = magyar 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV MT = Malti 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV NL = Nederlands 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV PL = polski 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV PT = português 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV RO = română 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV SK = slovenčina 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV SL = slovenščina 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV FI = suomi 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV SV = svenska 2017-09-07  
Symbioflor 2 Article-31 referral - Annex IV HR = Hrvatski 2017-09-07  
Symbioflor 2 Article-31 referral - Review started (English only) 2016-04-01  
Symbioflor 2 Article-31 referral - Notification (English only) 2016-04-06  
Symbioflor 2 Article-31 referral - CHMP list of questions (English only) 2016-04-06  
Symbioflor 2 Article-31 referral - Timetable for the procedure (English only) 2016-04-06 2017-03-24

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:
Opinion provided by Committee for Medicinal Products for Human Use

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